Patent Publication Number: US-2007099290-A1

Title: Customizable chip and method of manufacturing the same

Description:
TECHNICAL FIELD  
      The present invention relates to a chip allowing customization of its configuration and the method of producing it.  
     BACKGROUND ART  
      Recently, use of micro total analysis systems (μ-TAS) in which chemical operation such as the pretreatment of a sample, and its reaction, separation and detection is performed on a microchip has rapidly advanced. Such micro total analysis systems allows the use of a small amount of sample, imposes less burden to the environment, and enables high sensitivity analysis. Thus, if it were possible to apply such microchip based analysis to the clinical laboratory test in medicine, it would be highly advantageous because then the laboratory test could be easily performed on tiny amounts of samples.  
      Non-patent Document 1: David, S. J., Dwight, K. O., and Wayne, R. D. (Eds.), 2001, “Laboratory Test Handbook with Key Word Index,” 5th edition, Lexi-Comp Inc., Hudson, Ohio, pp. 77-80  
     DISCLOSURE OF THE INVENTION  
      If micro total analysis systems were applied to the clinical laboratory test and the like, the number of tests achievable on a single chip would be limited by the size of the chip. Generally, the clinical laboratory test must determine many clinical parameters for a given purpose. For example, number of the clinical parameters determined by a general biochemical test is as many as 150 (Non-patent Document 1). If parameters related with tumor markers and allergens were added to the above, the number would rise up to 300. In addition, the clinical parameters vary according to the individual patient, and his/her disease condition.  
      If a laboratory of a certain clinical center meets such widely varied requirements from clinics by using chips, the laboratory will have to prepare such a huge number of chips as to enable the laboratory to meet widely varied combinations of clinical tests. Thus, such analysis system, could never been put into practice. In addition, a chip having one definite layout cannot meet two or more different combinations of tests.  
      The present invention was proposed in view of the above situation, and aims to provide a general-purpose analysis portion receptive to customization to meet a given test item, analysis chip, and production method thereof.  
      The term “chip” in the specification refers to a substrate having a function allowing one to perform predetermined operation on a sample placed thereupon. A chip according to the invention may have, for example, a channel groove on its surface so that a liquid sample can move along it. Movement of a liquid sample may be achieved via capillary action, or may be driven by external force such as electric field or pressure. If movement of a liquid sample along a channel is achieved by capillary action, it will be possible to dispense with the use of a unit for applying external driving force, and to move the liquid sample in a downstream direction solely dependent on the construction of the chip itself.  
      According to the invention, there is provided a chip comprising: a substrate; plural channels formed on the substrate; and a flow control portion which is provided to the plural channels and is capable of being closed, wherein closure of the flow control portion of a channel among the plural channels allows a sample to be guided to other channels.  
      The term “flow control portion capable of being closed” as used herein refers to the flow control portion capable of intercepting the passage of liquid by using a physical or a chemical treatment at the site where the flow control portion resides. Interception of liquid includes not only the complete occlusion of liquid but also partial passage of liquid downstream. Incidentally, if it is required to completely intercept the flow of liquid along a channel, the flow control portion is completely closed.  
      The chip of the invention is so constructed that the channel is provided with a closure-able flow control portion and when the flow control portion of one channel is closed, a liquid sample is guided to flow along the other channel. Because of this arrangement, it is possible to close desired channels and select desired channels for sample passage depending on the given use purpose of the chip or the property of the sample. Thus, it is possible to customize the configuration of the chip, despite that the structure itself of the chip is very simple.  
      It is possible to customize the configuration of a chip by setting an opening or a closing the flow control portions, thereby obtaining chips for the different test items. Thus, it is possible to readily obtain a chip whose channel configuration is most suitable for achieving the test required for a given patient or for determining the required clinical parameters. Since the chip includes flow control portions, it makes it unnecessary to prepare in advance a huge number of chips with different lay-outs corresponding to s huge number of test parameters. Because of the above-cited advantages, it is possible according to the invention to stably produce general-purpose chips receptive to customization at a low cost. Moreover, it is possible according to the invention to distribute a sample only to necessary channels by providing the flow control portion, which will allow the efficient use of the sample. Therefore, even if the amount of a sample is very small, it will be possible to reliably perform necessary tests on that sample. It is also possible to minimize the consumption of reagents required for analysis.  
      According to the invention, it is also possible to construct each flow control portion such that its closure can be modified at a post-processed state. This makes it possible to selectively close the desired flow control portion in accordance with the parameters required for a given test at a post-processing stage. Thus, it is possible to customize the configuration of a chip in accordance with an test item.  
      According to the invention, there is provided a chip comprising: a substrate; a sample introduction portion formed on the substrate; an analysis portion for analyzing a specified component contained in a sample introduced via the sample introduction portion; plural channels connecting the sample introduction portion with the analysis portions; and a flow control portion which is provided to the channels and is capable of being closed, wherein closure of the flow control portion of a channel among the plural channels allows a sample to be guided via other channel to the analysis portion.  
      In the invention, the analysis portion is connected via a flow control portion to a channel. At the analysis portion, analysis of a component in a sample is performed. When a sample is introduced via the sample introduction portion, the sample flows along a channel, and reaches an analysis portion for which the flow control portion connected thereto is open. When the chip further includes a pretreatment portion, a separation portion and a reaction portion, which will be described later, the chip is configured so that the sample passes through these portions before it reaches the analysis portion.  
      In the chip of the invention, the analysis portion or the separation portion which will be described later may work being driven by force applied externally, but they are preferably configured to work automatically, that is, separate a predetermined component and analyze the separated component in a specified order, driven by the inflow of sample. Realization of such automatic operation will be possible by utilizing capillary action or water-level difference as a driving force of a liquid sample. By utilizing capillary action, it is possible to make a sample introduced via the sample introduction portion flow through a channel automatically to an analysis portion to be analyzed there.  
      The chip of the invention includes plural channels each of which has its own flow control portion connected thereto. Because of this arrangement, it is possible to keep open a desired channel selectively among the plural channels while closing the flow control portions connected to the remaining channels. Thus, it is possible for a sample introduced via the sample introduction portion to pass through the desired route to reach an analysis portion.  
      According to the invention, there is provided a chip comprising: a substrate; a sample introduction portion formed on the substrate; analysis portions for analyzing a specified component contained in a sample introduced via the sample introduction portion; a branched channel for guiding the sample introduced via the sample introduction portion to the plural analysis portions; and a flow control portion which is provided to the channels and is capable of being closed, wherein closure of the flow control portion of a channel branched towards one of the analysis portion allows a sample to be guided to other of the analysis portions.  
      A chip of the invention has plural analysis portions each of which is in communication with a channel with its own flow control portion. Because of this arrangement, it is possible for a sample introduced via the sample introduction portion to be selectively transported only to a desired analysis portion. Thus, it is possible to supply a sample only to the analysis portions, among all the analysis portions for a plurality of test items, responsible for the determination of parameters required for a given test item. Accordingly, even if a sample is small in amount, it is possible to reliably select and determine the parameters required for a given test.  
      According to the invention, the flow control portion may be constructed such that its closure is achieved by clogging a part of the channel. Alternatively, in the chip according to the invention, closure of the flow control portion may be achieved by hydrophobizing the surface of the channel. These arrangements will ensure the reliable closure of the flow control portion.  
      The chip according to the invention may further include a separation portion which includes a part of a channel, and separate a component contained in a sample introduced via the sample introduction portion to guide the component to an analysis portion. Because of this arrangement, it is possible to reliably separate a predetermined component from a sample, and to supply the component to a selected analysis, which will increase the analysis sensitivity.  
      The chip according to the invention may further include a pretreatment portion upstream of the separation portion which will apply specified pretreatment on a sample introduced via the sample introduction portion. This arrangement will make it possible to apply pretreatment on a sample on the chip. Accordingly, it will be possible to render the sample more suitable for analysis subsequently performed. Further, in the invention, the pretreatment potion has the aforementioned flow control portion. Because of this arrangement, it will be possible to customize pretreatments performed by preparing a number of layouts suitable for a plurality of pretreatments and closing appropriate flow control portions at a post-processing stage. Thus, it is possible to selectively perform pretreatments as appropriate in accordance with a given sample.  
      In the chip in the invention, the pretreatment portion includes a reservoir, and a liquid switch portion provided downstream of the reservoir which controls the flow of a liquid sample from the pretreatment portion to the separation portion, wherein the liquid switch portion includes a damming portion for damming a liquid in the reservoir, and a trigger channel which communicates with a channel close to the damming portion, and guides the liquid to the damming portion, and wherein a flow control portion may be provided to the trigger channel. Through this arrangement it is possible to more stably apply desired pretreatment to a sample.  
      The chip in the invention may further include a reaction portion where a component separated at the separation portion undergoes a specified reaction. Through this arrangement it is possible to analyze a sample under condition more suitable for measurement. The reaction portion may also include the aforementioned flow control portion. Through this arrangement it is possible to customize the kinds of reactions performed at the reaction portion by preparing in advance reaction portions responsible for the occurrence of various reactions, and closing the flow control portion at a post-processing stage. Therefore, it is possible to allow the reactions to occur that are selected appropriately in accordance with a sample.  
      In a chip of the invention, the reaction portion includes a reservoir and a liquid switch portion provided downstream of the reservoir, the liquid switch portion includes a damming portion for damming the flow of a liquid in the reservoir, and a trigger channel which communicates with a channel close to the damming portion, and guides the liquid to the damming portion, and a flow control portion may be provided to the trigger channel. Through this arrangement, it is possible to allow a sample to undergo desired reactions sequentially.  
      In the invention, the flow control portion has a larger width than a channel connected thereto so that it can intercept the passage of flow through the channel. Through this arrangement, it is possible to selectively close a channel.  
      In the invention, part of the flow control portion may be open to outside. For example, a chip of the invention may further include a lid for covering the top surface of the channel such that when the lid is put in place there is formed an opening over the flow control portion. Through this arrangement it is possible to reliably close the flow control portion through the opening at a post-processing step.  
      According to the present invention, there is provided a chip including a substrate, and plural channels formed on the substrate, wherein some of the plural channels are closed.  
      In the chip of the invention, since a piece of plural flow control portions are closed, movement of sample to downstream through the closed portion is prevented. Because of this, passage of sample only to selected open channels is permitted.  
      According to the present invention, there is provided a method for producing a chip including preparing a substrate on which plural channels are formed, and closing some of the channel.  
      The method for producing a chip in the invention includes the closing a piece of a channel. According to this method, it is possible to stably produce chips in which movement of sample to downstream through the closed portions will be securely prevented. Therefore, it is stably reproduce the configuration of passage on the substrate appropriate for a sample.  
      In the method for producing a chip in the invention, the closing a channel may include hydrophobizing a part of the channel. By so doing it is possible to further enhance the closure of a part of the channel. Therefore, it is possible to more stably produce customized chip.  
      In the method for producing a chip in the invention, the closing a channel may include deforming a part of the channel to intercept it. By so doing it is possible to more reliably close the channel.  
      In the method for producing a chip in the invention, the closing a channel may include a sealing a part of the channel. It is possible to reliably intercept the flow of liquid through the channel by sealing a part of the channel. This ensures the reliable closure of a part of the channel. Sealing a channel used herein means closing the cross-section of a channel with a sealing material.  
      In the invention, the portion close to the damming portion may be placed at the damming portion itself or downstream of the damming portion. Through this arrangement it is possible to more reliably intercept the flow of liquid through the passage.  
      The above description has been given on the premise that closure of the flow control portion provided to a channel leads to the passage of sample to the other channels. According to an embodiment of the invention, however, it is also possible to prepare a group of flow control portions capable of opening, and to open some of the flow control portions so that sample can pass to the channels connected to those open flow control portions. Through this arrangement, it is possible to select channels to be opened according to the requirement from a given test and to only open the selected channel at a post-processing stage, so that sample may be guided to those selected channels. Thus, it is possible to customize the configuration of a chip according to the reagents used and analysis items.  
      To execute at site a test appropriate for a given patient, it is necessary to have a large-scale facilities. If a comparatively small clinical center or laboratory wants to execute a test, by preparing in advance general-purpose chips applicable to widely used items and combination analysis thereof, and customizing the configuration of the chip as appropriate, the test required for a given patient can be performed in the small-scale facilities.  
      For example, if a small clinical center prepares in advance one or more kinds of general purpose chips, even if it is difficult to own relatively large scale facilities, by appropriately setting an opening and a closing of the flow control portions, or setting predetermined reagents to the chip as appropriate, so as to customize the configuration of chip in accordance with the medical condition and its course of a patient. Therefore, it is possible to give a simple and quick analysis suitable for a given patient quickly at site. The analysis portion of a chip and chip itself enabling such customization will be described below.  
      According to the present invention, there is provided a general-purpose analysis portion comprising a main channel; a reservoir; a channel connecting the reservoir and the main channel; a damming portion provided to the channel for damming a liquid in the reservoirs; a trigger channel in communication at or close to the damming portion with the channel, the trigger channel being for guiding the liquid to the damming portion; a liquid switch portion including the damming portion and the trigger channel; a closing switch for closing the channel; a lag channel provided to trigger channel or channel; and a flow control portion for setting an opening and a closing of the channel or the trigger channel.  
      In the general-purpose analysis portion of the invention, sample moves past the main channel and channel to reach the reservoir and be used for a predetermined analysis. The constitutional member of the general-purpose analysis portion of the invention may be standardized according to the envisioned analysis items. Thus the analysis portion may be preferably used as the general-purpose analysis portion. In the general-purpose analysis portion of the invention, a trigger channel is provided for the purpose of setting an opening and a closing of the channel or the trigger channel. When at least a part of the flow control portion is opened, liquid can pass through the flow control portion, while a flow control portion is completely blocked, liquid cannot pass though the flow control portion. Thus, it is possible to set the route of the liquid by setting the opening and the closing of the flow control portions. Thus, the chip in the invention can be customized in accordance with a given sample for the analysis or a given test.  
      The liquid switch portion is a switching mechanism for controlling a flow of a liquid such as sample or a buffer in the channel. In the liquid switch portion, a liquid flowing along the channel is intercepted at its damming portion. The damming portion may be so constructed as to absorb a liquid thereby holding the liquid. Alternatively, the damming portion in itself may be lyophobic to the flowing liquid, and may be so constructed that the liquid is intercepted on its upstream side. The liquid switch portion includes the trigger channel. Liquid intercepted by damming portion goes beyond the damming portion to flow downstream, when it contact with the liquid passing through trigger channel.  
      Since the liquid switch portion is provided to the channel, introduction of a sample from the channel to the reservoir is controllability achieved. With a general-purposed analysis portion as described above, it is possible to obtain desired analysis result because predetermined reactions necessary for analysis are allowed to stably occur under the desired condition. It is also possible by providing a liquid switch portion to drive a plurality of process steps by capillary action sample once a sample is introduced into the system, without resorting to any external supporting apparatus.  
      The lag channel is provided to a predetermined portion of the channel or the trigger channel for producing a delay in the time distance of a sample flowing from one region to another region. Introduction of a lag channel further facilitate the condition of the reaction required for the analysis, and the like.  
      The closing switch has a valve structure configured so that it is closed when the predetermined amount of the liquid is introduced into the channel or the trigger channel to which the closing switch is. In the general-purpose analysis portion in the invention, thanks to the valve structure, only a certain predetermined amount of liquid is permitted to flow through a given channel or trigger channel to the reservoir and also counter current of the liquid is prevented.  
      In the general-purpose analysis portion of the invention, the reservoir may hold a reagent. Then, it is possible to more efficiently execute analysis using the reagent in the general-purpose analysis portion.  
      The general-purpose analysis portion of the invention may include two of the reservoirs, one of the liquid switch portion, one of the closing switch, one of the delaying channel, and one or two of the flow control portions. Alternatively, the general-purpose analysis portion of the invention may include five of the reservoirs, two or more of the liquid switch portions, two or more of the closing switches, two or more of the delaying channels, and two or more of the flow control portions.  
      The general-purpose analysis portion in the invention may take varied configurations. Typical configuration is, for example, divided into the following three types: a first type general-purpose analysis portion described in the following (I), a second type general-purpose analysis portion described in the following (II), and a third type general-purpose analysis portion described in the following (III). The general-purpose analysis portion described in the following (I) to (III) have the aforementioned main channel and the aforementioned channel, and further has the following structure.  
      (I) First Type General-Purpose Analysis Portion  
      It includes one of said reservoir and one of the flow control portion. It may further have one of the closing switch.  
      (II) Second Type General-Purpose Analysis Portion  
      It includes at least two of the reservoirs, at least one of the flow control portion, at least one of the closing switch, at least one of the liquid switch, and at least one of the lag channel.  
      (III) Third Type General-Purpose Analysis Portion  
      It includes at least five of the wells, two or more of the liquid switch portions, two or more of the lag channels, two or more of the flow control portions, and one or more of the closing switch.  
      The structure of the above (I), (II) and (III) can mainly be used to an analysis of a predetermined component in a sample with one-step reaction, two-step reaction, and three-step reaction, respectively.  
      According to the present invention, there is provided a chip including a substrate, and a general-purpose analysis portion formed on the substrate. The chip of the invention, because of its including the aforementioned general-purpose analysis portion, is amenable to standardization, can be customized according to individual needs, and suitably used as a general-purpose chip. According to the inventive chip, it is possible to customize the configuration of a chip by opening/closing the flow control portions according the parameters required for a given test. Thus, it is possible to reliably perform a required test using only a minimum amount of reagent and sample.  
      The chip of the invention may include a plurality of the general-purpose analysis portions. By so doing, it is possible to standardize the configuration of the chip for plural analyses, which further enhances the utility of the chip. It is also possible to customize the configuration of a chip to match a given test for an examiner by setting the opening/closing-state of the flow control portions at a post-processing stage. In other words, the chip of the invention can be customized in accordance with the personal needs of individual users.  
      The configuration of a chip of the invention can be modified in widely different manners, but the chip may configured as following and the different configurations of a chip may be classified according to the type of disease.  
      (i) Chip for the Diagnosis of Diabetes Set  
      Provided is a configuration which has an analysis portion including at least one of the third type general-purpose analysis portion and at least three of the first or the second type general-purpose analysis portions, at least one has a reservoir holding a reagent, wherein, when the third type general-purpose analysis portion has the reagent, the reagent being necessary for the detection of anti glutamate decarboxylase antibody, and when the first or the second general-purpose analysis portion has the reagent, the reagent being stored is necessary for determining any one, or two or more test items selected from the group consisting of hemoglobin A1c, 1,5-anhydro-D-glucitol, and glycoalbumin.  
      (ii) Chip for the Diagnosis of Obesity Set  
      Provided is a configuration which has an analysis portion including at least eight of the first or the second type general-purpose analysis portions, at least one of the second type general-purpose analysis portions has a reservoir holding a reagent, wherein the reagent is necessary for determining any one, or two or more test items selected from the group consisting of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, neutral fatty acid, HDL cholesterol, fasting blood sugar (glucose), and hemoglobin A1c.  
      (iii) Chip for the Diagnosis of Hyperlipidemia  
      Provided is a configuration which has an analysis portion including at least nine of the first or the second type general-purpose analysis portions, at least one of the nine of the first or the second type general-purpose analysis portions has a reservoir for holding a reagent, wherein the reagent is necessary for determining any one, or two or more test items selected from the group consisting of remnant lipoprotein cholesterol, LDL-cholesterol, lipoprotein a, apoprotein A-I, apoprotein A-II, apoprotein B, apoprotein C-II, apoprotein C-III, apoprotein E, creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamine transpeptidase, and necessary for determining two or more test parameters.  
      In the above chip (iii), at least one of the nine second type general-purpose analysis portions has a reservoir for holding a reagent, wherein the reagent is necessary for determining any one, or two or more test items selected from the group consisting of remnant lipoprotein cholesterol, LDL-cholesterol, lipoprotein a, apoprotein A-I, apoprotein A-II, apoprotein B, apoprotein C-II, apoprotein C-III, and apoprotein E. The chip may further include, in addition to the nine general-purpose analysis portions, a general-purpose analysis portion that has a reservoir for holding a reagent, wherein the reagent is necessary for the detection of creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamine transpeptidase. With this chip, it is possible to collect more accurate data necessary for hyperlipidemia including when the patient internally takes a therapeutic agent. The above chip (iii) may include an analysis portion including at least 13 of the first or the second general-purpose analysis portions.  
      (iv) Chip for the Diagnosis of Disordered Hepatic Function  
      Provided is a configuration which has an analysis portion including at least two of the third type general-purpose analysis portion, and at least eight of the first or the second type general-purpose analysis portions, at least one of the third type general-purpose analysis portion has a reservoir for holding a reagent, wherein, when the third type general-purpose analysis portion has the reagent, the reagent is necessary for determining any one, or two or more test items selected from the group consisting of HBs antibody, and HCV antibody, and when the first or the second type general-purpose analysis portion has the reagent, the reagent necessary for determining any one, or two or more test items selected from the group consisting of alkaline phosphatase, lactate dehydrogenase, total protein, albumin, agent for zinc phosphate turbidity test, agent for thymol turbidity test, choline esterase, and total bilirubin.  
      (v) Chip for the Diagnosis of Nephrosis  
      Provided is a configuration which has an analysis portion comprising at least seven of the first or the second type general-purpose analysis portions, at least one of the first or the second type general-purpose analysis portions has a reservoir for holding a reagent, wherein the reagent is necessary for determining any one, or two or more test items selected from the group consisting of total protein, albumin, urea nitrogen, creatinine, sodium ion, potassium ion, and chlorine ion.  
      (vi) Chip for the Diagnosis of Hypertension  
      Provided is a configuration which includes an analysis portion including at least two of the third type general-purpose analysis portion, and at least five of the first or the second type general-purpose analysis portions, at least one has a reservoir for holding a reagent, wherein, when the third type general-purpose analysis portion has the reagent, the reagent is selected from the group including agent for determining renin activity, and aldosterone, and when the first or the second type general-purpose analysis portion has the reagent, the reagent is necessary for determining any one, or two or more test items selected from the group consisting of nitrogen urea, creatinine, sodium ion, potassium ion, and chlorine ion.  
      (vii) Chip for the Diagnosis of Anemia Set  
      Provided is a configuration which includes an analysis portion comprising at least two of the third type general-purpose analysis portion, and at least two of the first or the second type general-purpose analysis portions, at least one has a reservoir for holding a reagent, wherein, when the third type general-purpose analysis portion has the reagent, the reagent is necessary for determining any one, or two or more test items selected from the group consisting of vitamin B12, and folic acid, and when the first or the second type general-purpose analysis portion has the reagent, the reagent is necessary for determining any one, or two or more test items selected from the group consisting of.  
      (viii) Chip for the Diagnosis of Gout  
      Provided is a configuration which includes an analysis portion comprising at least one the first or the second type general-purpose analysis portions, at least one holds a reagent necessary for the detection of uric acid.  
      (ix) Chip for the Diagnosis of Disorder of Thyroid Function  
      Provided is a configuration which includes an analysis portion comprising at least three of the third type general-purpose analysis portions, at least one of the third type general-purpose analysis portions has a reservoir for holding a reagent, wherein the reagent is necessary for determining any one, or two or more test items selected from the group consisting of triiodothyronine, thyroxine, and thyroid gland stimulating hormone.  
      (x) Chip for Determining the Activity of Adrenal  
      Provided is a configuration which includes an analysis portion comprising at least one of the third type general-purpose analysis portions which has a reagent necessary for the detection of cortisol.  
      The chip of the invention may be so constructed as to have the same number of general-purpose analysis portions with that for a sample, and may be subjected to the same analysis task using a standard solution instead of the sample. The result obtained by the chip from the standard solution may be compared with the result obtained by the test chip using a sample. The comparison will further enhance the accuracy of the diagnosis by the test chip.  
      The present invention provides an analysis chip allowing customization of the chip layout in accordance with test items, general-purpose analysis portion, and method for producing such a chip and analysis portion. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The object of the invention described above, and other objects, and its features and advantages will be further apparent by reading the following description of preferred embodiments with reference to the attached drawings.  
       FIG. 1  shows a block diagram for representing the functional components of a chip representing an embodiment of the invention.  
       FIG. 2  shows the configuration of a chip capable of achieving the functions as represented in  FIG. 1 .  
       FIG. 3  shows a cross-section of the chip shown in  FIG. 2  cut along line A-A′.  
       FIG. 4  shows a cross-section of the chip of  FIG. 2  cut along line B-B′.  
       FIG. 5  shows a cross-section of the chip of  FIG. 2  cut along line B-B′.  
       FIG. 6  shows a cross-section of the chip of  FIG. 2  cut along line C-C′.  
       FIG. 7  illustrates how a flow control portion of a chip is closed according to an embodiment of the invention.  
       FIG. 8  further illustrates how the flow control portion of a chip is closed according to the embodiment of the invention.  
       FIG. 9  still further illustrates how the flow control portion of a chip is closed according to the embodiment of the invention.  
       FIG. 10  shows a block diagram for representing the functional components of a chip representing another embodiment of the invention.  
       FIG. 11  shows the configuration of a chip capable of achieving the functions as represented in  FIG. 10 .  
       FIG. 12  shows the structure of measurement unit of the chip shown in  FIG. 11 .  
       FIG. 13  further shows the structure of measurement unit of the chip shown in  FIG. 11 .  
       FIG. 14  shows a diagram for schematically showing the structure of a measuring apparatus representing an embodiment.  
       FIG. 15  shows how a chip is inserted into the measuring apparatus shown in  FIG. 14 .  
       FIG. 16  shows the structure of a measuring apparatus representing an embodiment.  
       FIG. 17  shows the structure of a chip representing an embodiment.  
       FIG. 18  shows a cross-section of the chip shown in  FIG. 17  cut along line D-D′.  
       FIG. 19  shows a block diagram for representing the functional components of a chip representing an embodiment of the invention.  
       FIG. 20  shows a block diagram for representing the functional components of another chip representing an embodiment of the invention.  
       FIG. 21  shows a diagram for representing the components of a chip further including a separation unit representing an embodiment.  
       FIG. 22  shows the structure of separation region of the chip shown in  FIG. 21 .  
       FIG. 23  illustrates the method of molecular separation occurring at the separation region shown in  FIG. 22 .  
       FIG. 24  shows the structure of a chip representing an embodiment.  
       FIG. 25  shows the structure of the mixing portion of the chip shown in  FIG. 24 .  
       FIG. 26  shows the structure of the mixing portion of the chip shown in  FIG. 24 .  
       FIG. 27  shows enlarged views of the liquid switch portion shown in  FIG. 26 .  
       FIG. 28  shows the damming portion of the liquid switch portion shown in  FIG. 26 .  
       FIG. 29  shows the structure of the trigger channel of the chip representing an embodiment.  
       FIG. 30  shows a block diagram for representing the functional components of a chip representing an embodiment of the invention.  
       FIG. 31  shows a block diagram for representing the functional components of another chip representing an embodiment of the invention.  
       FIG. 32  shows the structure of a chip representing an embodiment.  
       FIG. 33  shows the pretreatment unit of the chip shown in  FIG. 32 .  
       FIG. 34  shows a block diagram for representing the functional components of a chip representing an embodiment of the invention.  
       FIG. 35  shows a block diagram for representing the functional components of another chip representing an embodiment of the invention.  
       FIG. 36  shows the structure of a chip representing an embodiment.  
       FIG. 37  shows the structure of the reaction unit of the chip shown in  FIG. 36 .  
       FIG. 38  shows the structure of the detection unit of a chip representing the sixth embodiment.  
       FIG. 39  shows a schematic diagram for showing an exemplary chip manufacturing system representing ninth embodiment.  
       FIG. 40  shows a schematic diagram for showing another exemplary chip manufacturing system representing an embodiment.  
       FIG. 41  illustrates how the flow of sample through a flow control unit is intercepted according to an embodiment of the invention.  
       FIG. 42  further illustrates how the flow of sample through the flow control unit is intercepted according to the embodiment of the invention.  
       FIG. 43  shows the organization of a chip manufacturing system representing an embodiment.  
       FIG. 44  shows the procedures for the manufacture of a chip representing an embodiment.  
       FIG. 45  shows the structure of separation unit of the chip shown in  FIG. 21 .  
       FIG. 46  shows the structure of separation region of the chip shown in  FIG. 21 .  
       FIG. 47  shows plane views for showing the structure of a trigger channel of a chip representing an embodiment.  
       FIG. 48  shows plane views for showing the structure of a trigger channel of a chip representing an embodiment.  
       FIG. 49  shows a plane view for showing the structure of the detection unit of a chip representing an embodiment.  
       FIG. 50  shows a plane view for showing the structure of the detection unit of a chip representing the fifth embodiment.  
       FIG. 51  shows sectional views for showing the structure of a chip having a detection unit as depicted in  FIG. 50 .  
       FIG. 52  shows a plane view for showing the structure of the closing switch in the detection unit of a chip representing the sixth embodiment.  
       FIG. 53  shows a plane view for showing the structure of a liquid switch portion of a chip having a detection unit as depicted in  FIG. 50 .  
       FIG. 54  shows a list of principal test items required for a recheck test, involved measuring methods, and applicable class of reaction unit.  
       FIG. 55  shows another list of principal test items required for a recheck test, involved measuring methods, and applicable class of reaction unit.  
       FIG. 56  shows yet another list of principal test items required for a recheck test, involved measuring methods, and applicable class of reaction unit.  
       FIG. 57  shows yet another list of principal test items required for a recheck test, involved measuring methods, and applicable class of reaction unit.  
       FIG. 58  shows a plane view for showing the structure of the detection unit of a chip representing an embodiment. 
    
    
     BEST MODE FOR CARRYING OUT THE INVENTION  
      The present invention will be described by means of embodiments with reference to the attached drawings. Throughout the drawings, every common element is represented by the same symbol, and its explanation will be not be repeated as appropriate.  
      At first, the basic structure of a chip receptive to customization upon which analysis of a sample will be made will be described in first and second embodiments. A chip includes, as its basic components, a sample introduction unit, flow control unit, and analysis unit. The analysis unit is a site where analysis of a component separated from a sample is performed. The analysis unit may also act as a detection unit when reaction is allowed to occur there to generate a visible product that indicates the presence of a target component. The analysis unit may also act as a measurement unit for storing a sample component that will serve as a subject to be analyzed by an external measuring device. The first embodiment represents a chip where the analysis unit serves as the detection unit while the second embodiment a chip where the analysis unit serves as the measurement unit. The structural details of the flow control unit will be described in the following embodiments.  
     First Embodiment  
      This embodiment represents a chip that enables the determination of some parameters selected from available plural test items. The chip includes plural detection units responsible for the determination of respective test items, which will also serve as analysis portions. Each detection unit is in communication with a dispensing channel to which is provided a flow control unit which determines whether downward flow of liquid through the dispensing channel should be permitted or not. The chip is configured such that a sample is guided only to the detection units responsible for the determination of test items required for a given test, by setting an opening and closing of the flow control units connected to relevant detection units.  
       FIG. 1  shows a block diagram for representing the functional components of a chip representing the first embodiment. The chip shown in the  FIG. 1  allows one to analyze the elements of a sample, and includes a sample introduction unit  212 , a flow control unit  312 , and a detection unit  214 . The chip  311  includes a substrate made, for example, of silicon, glass, quartz, various plastic materials, or elastic materials such as rubber, and has an analysis system formed on its surface. The analysis system may be obtained by forming plural grooves on a surface of the substrate, placing a top member over the grooves to seal them, and providing, to the resulting closed channels, members and channels connecting those members so as to achieve the functions as shown in  FIG. 1 .  
       FIG. 2  shows an exemplary configuration of a chip  311  capable of achieving the functions as represented in  FIG. 1 . The chip  313  shown in  FIG. 2  includes, on a surface of a substrate  216 , an inlet  217 , a main channel  221 , dispensing channels  222 , flow control units  314 , detection reservoirs  223 , and a reservoir  224 .  FIG. 3  shows a cross-section of the chip shown in  FIG. 2  cut along line A-A′.  FIG. 3  shows only the layered structure of the chip including substrate  216 , lid  226  and seal  227  with the constitutive members such as the main channel  221  not being represented. The chip  313  has a lid  226  over the substrate  226 . To the lid  226 , are provided vent holes  225  communicating with the reservoir  224  and respective detection reservoirs  223 . The top surface lid  226  may be sealed with a seal  227  to prevent the entry of contaminants including dust.  FIG. 3  represents a cross-section of a chip having the seal.  
      The substrate  216  may have an area of 3 to 10 cm×2 to 7 cm, for example. It may have a thickness, for example, of 0.5 mm to 1 cm. The lid  226  may be made of the same material with the one constituting the substrate  216 . The surface of substrate  216  and bottom surface of the lid  226 , that is, the joining surfaces to the substrate  216  are preferably hydrophilic. Because then it is possible for a sample to be introduced into and move within the chip  313  via capillary action, without requiring the use of an external driving unit such as a pump or electrodes, and thus it is possible to simplify the structure of the system.  
      Each of the main channel  221  and dispensing channels  222  may have a cross-section of 100 μm in width and 20 μm in depth. Each detection reservoir  223  may have a cylindrical shape with a diameter of 2 mm, or rectangular shape with the side of 2 mm. The detection reservoir  223  may have the same depth with that of the dispensing channel  222 , or may be as large as but slightly smaller than the thickness of the substrate. When optical measurement is performed on the detection reservoir  223  by radiating a beam onto the reservoir in a direction in parallel with the thickness of chip  313 , and detecting the presence of a target component in a sample, it is preferable for the detection reservoir  223  to have a depth about as large as that of the dispensing channel  222 , or as large as but slightly smaller than the thickness of the substrate, because then it is possible to lengthen the optical path, thereby enhancing the sensitivity of optical detection.  
      The vent hole  225  of a detection reservoir  223  is not necessarily provided on the top of the well, as long as the vent hole  225  is provided close to the well  223  in communication with the latter. The vent hole  225  may have a round cross-section, for example, with a diameter of 50 μm to 1 mm. By providing a vent hole to each detection reservoir  223 , it is possible to securely guide fluid to the well  223 . The surfaces of each vent hole  225  and its surrounds are preferably hydrophobic. Because then it is possible to prevent liquid poured into the detection reservoir  223  from leaking through the vent hole  225 . When the leak of liquid from the detection reservoir  223  is safely prevented, it is possible to ensure that liquid stored in that detection reservoir  223  has a constant volume as specified. Loss of the sample is also prevented.  
      The seal  227  may be made of any appropriate material, as long as it can be peeled off prior to the use of a chip  313  to which it is applied. For example, a sheet obtained by applying an emulsion-based adhesive such as vinyl acetate on any one chosen from various plastic materials, may be used. Alternatively, an epoxy-based or silicone-based adhesive may be used.  
      The inlet  217  corresponding to a sample introduction unit  212  is a portion through which a sample is introduced into the system, and takes the shape of a reservoir or a well on the chip  313 . The inlet  217  may be formed by preparing a cylindrical cavity with a diameter of about 3 mm in a substrate, preparing a circular throughhole of the same size on a lid  226  at a corresponding site, and putting the lid in place over the substrate.  
      The reservoir  224  serves as a waste reservoir and may be obtained by preparing a cylindrical cavity with a diameter of about 5 mm in a substrate, preparing a vent hole  225  on a lid  226  at a corresponding site, and putting the lid in place over the substrate. The surfaces of vent hole  225  of reservoir  224  and its surrounds are preferably made hydrophobic like those of vent holes  225  of detection reservoirs  223 . The vent hole  225  of reservoir  224  is not necessarily provided on the top of the reservoir, as long as the vent hole  225  is provided close to reservoir  224  in communication with the latter. The vent hole  225  may have a round cross-section, for example, with a diameter of 50 μm to 2 mm. The vent hole in question may have a round cross-section whose diameter is larger than the corresponding diameter of vent holes  225  of adjacent detection reservoirs  223 .  
      When a chip  313  is used for analysis, and has a seal  227  attached thereto, at first the seal  227  is removed. When the seal  227  is removed, the inlet  217  and vent holes  225  become open and exposed to external air. Then, a sample is introduced into the now opened inlet  217 . The sample introduced is guided via capillary action into the main channel  221 .  
      Various components contained in the sample that moves along the main channel  221  are distributed to dispensing channels  222  communicating with the main channel  221  to be guided to plural respective detection reservoirs  223  where they accumulate. The detection reservoirs  223  shown in  FIG. 2  correspond to the detection unit  214  shown in  FIG. 1 . The dispensing channels  222  and detection reservoirs  223  may be provided in their number as needed on a substrate  216 .  
       FIGS. 4A and 4B  show a cross-section of the chip of  FIG. 2  cut along line B-B′ with attention being paid to the detection unit  214  including a detection reservoir  223  as the main constructional member. Each of the detection reservoirs  223  shown in  FIGS. 4A and 4B  contains a detection reagent  231  in its bottom. The detection reagent  231  may be chosen such that when it is brought into contact with a specified component contained in a sample, it can give a color, emit light, change its color, be bleached, lose its light, or the like as a result of the interaction with the component. When a sample, after passing through a separation region  218 , reaches a detection reservoir  223 , a detection reagent  231  is dissolved or dispersed in a mobile phase, and undergoes the predetermined reaction with the sample in detection reservoir  223 , and the reaction is detected. When a chip has plural detection reservoirs  223  like the chip  313  shown in  FIG. 2 , one detection reservoir  223  may be put aside from the analysis using a detection reagent  231 , but used as a reference.  
      The detection reservoir shown in  FIG. 4A  is configured such that, when the sample develops a color and the like as a result of reaction, it can be visually confirmed through the lid  226 . The detection reservoit shown in  FIG. 4B  has a lid  226  protruded in profile which serves as a micro-convex lens  228  when viewed from top for enlarging the image of the interior of detection reservoir  223 . With this arrangement, it is possible to precisely check visually the change of sample solution such as development of color, emission of light, change of color, or bleaching or disappearance of color. Moreover, even if the detection reservoir  223  has a very limited area, it will be possible to reliably check the change of sample solution within such as development of color, emission of light, change of color, or bleaching or disappearance of color. This allows the amount of a sample required for analysis to be minimized.  
       FIGS. 5 and 6  show the structure of detection unit  214  representing another embodiment.  FIG. 5  shows a cross-section of the chip of  FIG. 2  cut along line B-B′, and  FIG. 6 a  cross-section of the chip of  FIG. 2  cut along line C-C′. As shown in  FIGS. 5 and 6 , a single micro-convex lens  228  may be extended to cover two or more detection reservoirs  223 . In this case, the micro-convex lens  228  may be, for example, of half-cylinder shape which will simplify the structure of lid  226 .  
      It is possible to supply a different detection reagent  231  to each of the plural detection reservoirs  223 . By virtue of this arrangement, it is possible, even when a sample contains plural components, to detect tcomponents via the corresponding detection reactions by using a single chip. Therefore, it is possible to determine multiple parameters required for a given test using a minimum amount of sample.  
      Turn again to the chip  313  of  FIG. 2 . From main channel  221  are sequentially branched off plural dispensing channels  222 . Since the dispensing channel  222  has a smaller cross-section than the main channel  221 , a sample is withdrawn via capillary action sequentially from the upstream dispensing channel  222  with their detection reservoir  223  to the downstream dispensing channels  222  with their detection reservoir  223 .  
      Each dispensing channel  222  is equipped with a flow control unit  314 . The flow control unit  314  is so constructed as to close the dispensing channel  222  connected thereto as needed, thereby intercepting the flow of sample therethrough to downstream side. Therefore, a sample is withdrawn only through dispensing channels  222  whose flow control units  314  are kept open so that selected detection reactions can occur at the detection reservoirs  223  connected to the dispensing channels  222 . On the contrary, the sample is not allowed to flow through the dispensing channels  222  whose flow control units  314  are kept closed and thus any detection reaction does not occur in the detection reservoirs  223  connected to those closed dispensing channels.  
      Unnecessary sample left after its necessary fraction being supplied through all the open dispensing channels  222  whose flow control units  314  are kept open to respective detection reservoirs  223  is evacuated into the reservoir  224 .  
      By providing flow control units  314  to respective dispensing channels  222 , it is possible to customize the configuration of chip  313  in accordance with the parameters to be determined for a given test. The detection reservoirs  223  in accordance with the expected clinical test items are provided in advance, a selective number of dispensing channels  222  are opened such that a sample can reach the detection reservoirs  223  which will give reactions responsible for the determination of the required items. On the other hand, according to this arrangement, the sample is prevented from entering unnecessary detection reservoirs  223 . Thus, it is possible to provide a sufficient amount of sample to each detection reaction required for the test while consuming a minimum amount of sample.  
      Preparation of a chip as depicted in  FIGS. 2 and 3  may be carried out, for example, via the procedures as described below. Grooves are formed on one surface of a substrate  216  to provide a main channel  221  and dispensing channels  222 . An inlet  217  in communication with the main channel  221  is also formed together with detection reservoirs  223  and a reservoir  224 . Formation of those channels and reservoir may be achieved by any appropriate means in accordance with the material of substrate  216 , for example, when the substrate  216  is made of a plastic material, the grooves and others may be formed by etching, press molding using a die such as emboss molding, injection molding, molding using a material capable of curing via the exposure to light, and the like. The width of main channel  221  may be determined as appropriate in accordance with the property of a sample submitted to the test. For example, if a sample contains a polymer component (For example, DNA, RNA, protein, or saccharide chain), the main channel  221  preferably has a width of 5 μm to 1000 μm.  
      To each dispensing channel  222  is provided a flow control unit  314 . The flow control portion  222  may have any desired structure as long as it can intercept the flow of liquid downstream through the dispensing channel  222  connected thereto as needed. For example, a flow control unit  314  may be formed by hydrophobizing a part of the dispensing channel  222 . FIGS.  7  to  9  are the cross-sections of dispensing channels  222  for showing how the dispensing channel  222  can be selectively hydrophobic to intercept the flow of sample through the channel.  
      A substrate  216  shown in FIGS.  7  to  9  is placed on a platform  322 . On the substrate  216  are provided three exemplary flow control units  314   a  to  314   c  as the flow control unit  314 . In the particular example shown in FIGS.  7  to  9 , the flow control unit  314   a  shall be closed while the flow control units  314   b  and  314   c  shall be kept open. Explanation will be given below how those flow control portions will see their assigned fates.  
      A flow control portion adjustment device  317  includes a pressing substrate  318  with a concave  321  having a size corresponding to that of a substrate  216 , printing rods  319 , and PDMS (polydimethyl siloxane) stamps  320 . Printing rods  319  are provided opposite to respective flow control units  314 , for example, with regard to the particular example shown in  FIG. 7 , to flow control units  314   a  to  314   c . Each printing rod  319  has a PDMS stamp  320  on its tip, and is inserted into the pressing substrate  318  to be freely slidable therethrough up to downward or vice versa as shown in the figures.  
      Operation of the flow control portion adjustment device  317  proceeds as shown in  FIG. 7  by projecting a printing rod  319  downward through the concave  321  towards a flow control unit  314  to be closed. In this particular example, since closure through flow control unit  314   a  is required, the printing rod  319  placed opposite to flow control unit  314   a  is projected to cavity  321  side.  
       FIG. 8  shows how the concave  321  is depressed until it engages with an underlying substrate  216  so that the flow control portion adjustment device  317  is pressed hard against the platform  322 . The PDMS stamp  320  of the projecting printing rod  319  is deformed so much that the flow control unit  314   a  is filled therewith.  
       FIG. 9  shows the profile of flow control portions when the flow control portion adjustment device  317  is removed from platform  322 . The flow control unit  314   a  has a thin layer  323  of PDMS formed on its surfaces as a result of the hard pressing of PDMS stamp  320  against it. Since the PDMS layer  323  is hydrophobic, sample flowing through the dispensing channel  222  connected to flow control unit  314   a  is prevented at that portion  314   a  from flowing further downstream. The band of hydrophobic PDMS layer  323  preferably has a width of 100 to 1000 μm.  
      According to this method, it is possible to reliably hydrophobize the surface of channels provided with flow control units  314  to be closed out of the flow control units  314  prepared on substrate  216  by bringing PDMS stamps  320  into contact with those flow control units  314 . Thus, it is possible to close flow control units  314  to be closed easily, securely and selectively. Movement of printing rod  319  may be achieved, for example, by hand. Alternatively, a control unit for controlling the position of individual printing rods  319  may be provided to flow control adjustment device  317  so as to further facilitate the selective activation of printing rods  319 . In this case, driving force necessary for moving selected printing rods  319  may be provided, for example, by a driving mechanism using a solenoid coil and magnet.  
      If the substrate  216  is made of a plastic material, it is possible to close a flow control unit  314  by using a printing rod with a heated stamp on its tip, and pressing the stamp against the flow control portion to cause a barrier to be formed there, thereby intercepting the channel.  FIGS. 41 and 42  illustrate how a heated stamp is utilized to close a flow control unit  314 .  
      As shown in  FIG. 41 , the stamp  320   a  attached to the tip end of printing rod  319  is heated to a temperature over the glass transition temperature of the constitutive material of substrate  216 , and then pressed against a flow control unit  314  from the substrate  216  side. The stamp  320   a  may be made, for example, of a wedge-shaped metal strip protruding to the end. Heating of the stamp  320   a  may be achieved by a heater unit incorporated in the printing rod  319 . The flow control unit  314  and its surrounds will soften via the contact with stamp  320   a , and when the stamp  320   a  is further thrusted into the underlying substrate  216 , the now softened resin constituting the substrate is pushed aside to form a bulge on the dispensing channel  222 .  
      When the stamp  320   a  is removed from the substrate  216 , and substrate  216  is cooled, the substrate  216  recovers its original hardness, and thus a barrier wall to seal and intercept dispensing channel  222  is formed as shown in  FIG. 42 .  
      According to this method, it is possible to readily seal the dispensing channel  222  and thus to intercept the flow reliably using a simple device. Then, it is possible to customize the configuration of a chip by providing the lay-out of the open/closure of individual flow control units  314 . The metal strip to be used as stamp  320   a  may have its surface treated with Teflon (registered trademark). This arrangement will inhibit the adherence of plastic material of substrate  216  onto the surface of metal stamp  320   a , which might otherwise occur when the metal stamp  320   a  is pressed hard against the substrate  216 .  
      In the particular example shown in  FIG. 42 , the re-hardened resin bulge protrudes above the top surface of substrate  216 , and such a bulge is preferably employed when the chip does not has a lid  226 . If the bulge is not so high as to protrude above the top surface of substrate  216 , removal of excess protrusion will be unnecessary even if the chip has a lid  226 , which will make it possible to efficiently customize the configuration of analysis system in accordance with a given test.  
      According to the method underlying the embodiment, it is possible to readily customize the configuration of analysis system quickly in a short period of time because it is possible to opening/closing individual flow control units  314  via simple operation.  
      Turn again to  FIGS. 2 and 3 . An inlet  217  and vent holes  225  are formed on a lid  226 .  
      The lid  226  is joined to the obtained substrate  216 . Then, a seal  227  is applied as needed over the top surface of lid  226 . Now, a chip  313  is obtained. Joining of lid  226  to substrate  216  may be achieved, for example, by apply a small amount of solvent to which the material of substrate  216  will dissolve onto the joining surfaces of substrate  216  and pressing the lid  226  against the surfaces of substrate  216 . Alternatively, joining of lid  226  to substrate  216  may be achieved by applying a ultrasonic wave to the joining surfaces after the lid is attached to the substrate, or via a predetermined adhesive. If the lid  226  and substrate  216  are made of a plastic material, joining of the two may be achieved by welding.  
      The wall surfaces of main channel  221  and dispensing channels  222  is preferably coated in order to supress the adherence of molecules such as DNA or proteins thereto. Such coating will enhance the separation performance of a chip  313 . Suitable materials for coating may include, for example, those that have a structure analogous to that of phospholipids constituting the cell membrane. It is also possible to supress the adherence of molecules such as DNA to the wall of channels, by coating the channel walls with a water-repellent resin such as fluorine contained resin, or with a hydrophilic substance such as bovine serum albumin. Or, a hydrophilic polymeric material such as MPC (2-methacryloyloxyethylphosphorylcholine) polymer or the like, or a hydrophilic silane coupling agent may be coated on the surface of a substrate  216 .  
      If MPC polymer is used for rendering a surface of a substrate  216  hydrophilic, Lipidure (registered trademark, manufactured by NOF Corporation) or the like may be used. If Lipidure (registered trademark) is used, it may be dissolved in a buffer solution such as TBE (Trisborate+EDTA) buffer at 0.5 wt %, and the resulting solution is filled in main channel  221  and dispensing channels  222 , and left for several minutes. Then, coating of the wall surfaces of those channels is achieved.  
      To further enhance the entry of a sample introduced via an inlet  217  into a channel  230 , it is effective to form a hydrophilic layer such as silicon oxide layer on the surface of channel  230 . It will be possible to smoothly introduce a buffer into a channel without the deliberate use of an external driving force, by forming a hydrophilic layer. Moreover, if at least the surface of the substrate  216  is made of a hydrophilic polymeric material such as PHEMA (polyhydroxyethylmethacrylate), it will be possible to prevent the non-specific adsorption of components contained in a sample to the surface of substrate  216 . This will ensure the secure sorting and detection of a sample, even if the sample is very small in amount.  
      Turn back to  FIG. 1 . As described above, by using a chip  311  represented by the embodiment, it is possible to choose the detection of a predetermined component in a sample in accordance with the kind of the sample as appropriate by using a single chip  311 . Thus, it is possible to carry out analysis only on the necessary parameters by using a minimum amount of sample.  
      Let&#39;s assume, for example, that in the chip  313  shown in  FIG. 2 , coloring reactions are allowed to occur at a plurality of the detection reservoirs  223 . By so doing, it is possible to check whether any specific component is present in a sample or at which concentration the component is present in the sample by calorimetric method. In this case, the substrate  216  is preferably made of a transparent material. This is because such arrangement will ensure more accurate detection. Suitable materials may include, to mention concrete examples, quartz, cyclic polyolefin, PMMA (polymethylmethacrylate), PET (polyethyleneterephthalate), and the like.  
      Detection of a composition using a chip  313  is suitable for the detection directly using a sample introduced via an inlet  217 . For this purpose, detection is preferably achieved at a single step in the detection reservoir  223 . Suitable parameter for such detection may include, for example, the detection of alanine aminotransferase (ALT) which is a liver enzyme in blood plasma.  
      Incidentally, for the useless detection reservoirs  223  of a chip  313 , that is, for the detection reservoirs  223  communicated with dispensing channels  222  whose flow control units  314  are closed, provision of detection reagents  231  may be omitted.  
      A chip  313  may be provided with another reservoir communicating with a main channel  221  so that the additional reservoir can contain buffer for diluting a sample or allow the introduction of buffer at a predetermined timing. By so doing it is possible to allow a sample to enter the system via inlet  217  to be diluted before it is guided to through dispensing channels  222  whose flow control units  314  are open as far as respective detection reservoirs  223 . This arrangement makes it possible to dilute a sample to a concentration suitable for the occurrence of detection reaction at the detection reservoir  223 , and thus to enable the highly sensitive measurement.  
      In the chip of this embodiment, it is possible to customize the configuration of the chip by selecting an opening/closing of flow control units  314 , and thus the chip can be used profitably for performing the clinical laboratory test and the like. For example, a test item required for a hospital or a laboratory test center is easily selected, and it is to provide a chip suitable for the analysis of the test item. If the combination of the test item can be online-ordered by the hospital or laboratory test center, it will be possible for the laboratory to easily prepare necessary numbers of the made-to-order chips configured for the received test items.  
      It is also possible for a hospital or laboratory test center to readily prepare at site a chip suitable for the test item for a patient. With a view of managing his/her health, a user may make on-line access to a chip manufacturer and inform the manufacturer of his/her necessary health check items. Then, the manufacturer will be able to provide the user with necessary numbers of chips customized for the user&#39;s request.  
      Production of a customized chip will be detailed in relation to a ninth embodiment.  
     Second Embodiment  
      This embodiment represents a chip that enables the selection of some parameters out of available plural parameters for the measurement by external measuring apparatuses. The chip includes plural measurement units responsible for the determination of respective detection parameters, which will also serve as analysis units. Each measurement unit is in communication with a dispensing channel to which is provided a flow control unit for adjusting the downward flow of liquid through the dispensing channel. The chip is configured such that a sample is guided only to the measurement unit responsible for the necessary parameters, by setting an opening and a closing of the flow control units connected to relevant measurement units.  
       FIG. 10  is a block diagram for representing the functional components of a chip representing this embodiment. A chip  315  is different from the one represented by the first embodiment in that it includes a measurement unit  233  instead of the detection unit  214 . The measurement unit  233  is a portion for storing a sample component that will be subjected to the measurement by an external measuring apparatus.  
       FIG. 11  shows the configuration of a chip  315  capable of achieving the functions as represented in  FIG. 10 . The basic structure of chip  316  shown in  FIG. 11  is similar to that of chip  313  ( FIG. 2 ) described in connection to the first embodiment, except that chip  316  includes fraction portions  235  instead of detection reservoirs  223 . The fraction portion  235  is a reservoir for a fraction of a sample introduced via inlet  217 .  
       FIGS. 12 and 13  show the structure of measurement unit  233  that has a fraction portion  235  as a major structure member. The fraction portion  235  may be constituted only of a reservoir for storing sample as shown in  FIG. 12 . The separation portion  235  may further contain a measurement reagent  236  as shown in  FIG. 13 . The measurement reagent may include the same substances that are utilized as detection reagents  231  in a chip  313  representing the first embodiment. By using the measurement reagent  236 , a specific element in sample is reliably analyzed by using a coloring reaction. To put it more specifically, it is possible to measure the intensity of light having a wavelength of 350 to 640 nm transmitted therethrough. Even when the measurement portion does not contain any measurement reagent like the one shown in  FIG. 12 , it is possible to select number of the fraction portions  235  used by setting the opening and closing of the flow control units  314  to meet the need of estimation for the bias value due to the coloration of the sample in itself.  
       FIG. 14  is a diagram for schematically showing the structure of a measuring apparatus  237  which will perform an optical measurement on a sample component in the fraction portions  235 , by receiving the insertion of chip  316 . The measuring apparatus  237  includes a socket  244  for receiving the insertion of a chip  316  and a measuring unit  242  for measuring the optical property of a sample in a fraction portion  235  of a chip  316  inserted into the socket  244  by irradiating a light thereto. The measuring unit  242  includes a light source  238 , a light condenser  243 , and photosensitive portion  239 . In FIGS.  14  to  16 , only two measurement units  242  and two fraction portions  235  are depicted for the convenience of illustration, but the measurement units  242  may be provided by the same number with that of the measurement units  233  provided on a chip  316 .  
      The size of measurement unit  242  may be determined in accordance with the size of fraction portion  235  related thereto. For example, it is possible to prepare a chip  316  where each fraction portion  235  has a depth of about 1 mm, and there is an interval of about 1 mm between any two adjacent fraction portions  235 . Then, each of the light source  238 , the photosensitive portion  239  and the optical filter  240  is designed to have a size matching the dimension of fraction portions  235 .  
      The light sources  238  may include, for example, an LED, laser diode, semiconductor laser, and so on. The action of light source varies depending on the wavelength for measurement, and thus the light source may be chosen as appropriate according to the wavelength of light emitted as a result of the coloring reaction based on a measurement reagent  236  under study. The light condenser  243  may be obtained, for example, by processing a self-focusing lens into a lens having a desired shape and size. Suitable photosensitive portion  239  may include a phototransistor, photoelectric cell, and so on.  
       FIG. 15  illustrates how a chip  316  is inserted into the measuring apparatus  237  shown in  FIG. 14 . When a chip  316  is inserted into the socket  244  of a measuring apparatus  237 , opposite to a measuring unit  242  is placed a corresponding fraction portion  235 . To satisfy this condition, the measuring apparatus has the measurement units  242  of the same in number with that of fraction portions  235  of a chip  316  it receives. Then, the fraction portions  235  of chip  316  will be placed opposite to their corresponding measurement units  242 , thereby enabling optical measurements to be performed on all the separation portions simultaneously, which will allow the measurement to be completed quickly. Alternatively, the measuring apparatus  237  may have a single measuring unit  242 . Then, it will be possible to achieve optical measurement by sliding the chip  316  through the socket  244  so that a plurality of the fraction portion  235  is sequentially measured.  
       FIG. 16  shows a variation of the measuring apparatus  237 . The measuring apparatus  237  shown in  FIG. 16  is similar in its basic structure to the apparatus shown in  FIG. 14 , but different in that it includes a single light source  238 , and further includes an optical filter  240  and light shield plate  241 . The measurement unit shown in  FIG. 16  lacks a light condenser  243 , but may have one.  
      Using the optical filter  240 , a light from the light source  238  and whose wavelength falls in a specified range can selectively be irradiate with to the fraction portion  235 . Because of this arrangement, it is possible, even when the light source  238  emits light consisting of components having a wide range of wavelengths, to select the components having wavelengths falling within a specified range using the optical filter  240  in accordance with the wavelength for a measurement, thereby using only those light components for the measurement. In addition, since the optical filter  240  is supported by a light shielding plate  241 , leak of a light from the measurement unit  242  irradiated from light source  238  to adjacent units  242  can be safely avoided.  
      The optical filter  240  may be obtained by cutting a material known as a material for optical filter to a specified size.  
      For the measurement apparatus  237  as shown in FIGS.  14  to  16 , instead of the fixed light source  238 , an optical fiber from a remote light source may be placed with respect to the measurement apparatus  237  such that it directs light from the light source to an assigned fraction portion  235 . The above explanation has been given on the premise that light from a light source transmits the fraction portion  235 . However, the measurement unit  242  may be constructed so as to monitor the absorption or scattering of light.  
      The configuration of chip  315  shown in  FIG. 10  is not limited to those described above, but may take many other variations. For a chip  316  where measurement units  233  is served as analysis units, it is possible to customize the configuration of the chip  316  in accordance with the parameters required for a given test by providing flow control units  314  to respective dispensing channels  222  communicating with the fraction portions  235  and opening/closing the flow control channels  314 . The chip  316  is allowed to have in advance fraction portions  235  prepared in accordance with the expected test items. Then, it is possible to allow a sample to flow through the dispensing channels  222  connected to the fraction portions  235  which are involved in the determination of necessary parameters while the sample is prevented from entering unnecessary fraction portions  235 . Thus, it is possible to provide a sufficient amount of sample required for the test while consuming a minimum amount of sample. Therefore, it is possible by using the measurement apparatus  237  to reliably perform necessary tests about the components of a sample via simplified procedures.  
      The configuration of chip  316  embodying the essence of the chip  315  shown in  FIG. 10  and that of the measurement apparatus  237  are not limited to those described above, but may include many variations.  
      For example, the chip may include a variation as shown in  FIG. 17  where each fraction portion  235  is placed over the corresponding dispensing channel  222 , and an optical waveguide  245  is placed beneath the fraction portion  235 . The optical waveguide  245  may be made of a quartz-based material or an organic polymer-based material. The optical waveguide  245  is made of a material having a higher refractive index than that of surrounding materials. In this case, light enters from the bottom of the chip into the optical waveguide  245 , and exits outside from the bottom of the chip.  FIG. 18  shows a cross-section of the chip shown in  FIG. 17  cut along line D-D′.  
      In this case, a light source may be provided on the bottom surface and the like of measuring apparatus  237  so that it directs light towards an optical waveguide for illumination  246 , while a photosensitive portion may be provided on the bottom surface and the like of measuring apparatus  237  to receive light emanating from an optical waveguide for sensor  247 . Then, the surface in which the optical waveguide for illumination  246  and the optical waveguide for sensor  247  are exposed may attached to the bottom surface and the like of measuring apparatus  237 , so as to guide the entry of light into the fraction portion  235  of a dispensing channel  222  and to receive light emanating from the fraction portion  235  for measurement.  
      The chip shown in  FIGS. 17 and 18  may be constructed so as to have the optical waveguide for illumination  246  and the optical waveguide for sensor  247  while being devoid of the optical waveguide  245 . With the chip of this configuration, light emanating from a light source is guided via the optical waveguide for illumination  246  to a fraction portion  235  which passes the light via the optical waveguide for sensor  247  to a photosensitive portion. With the chip of the above configuration, it is possible to perform optical measurement on a specified component in a liquid captured in the fraction portion  235 . Since the chip lacks the optical waveguide  245 , it is possible to simplify the structure of the chip.  
      The above explanation has been given on the premise that the measuring apparatus  237  uses, for detection, light transmitted through a fraction portion  235 . However, the photosensitive portion  239  may be constructed so as to use, for detection, light reflected from a fraction portion  235 .  
      Instead of being applied to the measuring apparatus  237  for measurement, the chip  316  may be constructed so that an aliquot can be dispensed from sample captured in a fraction portion  235  of the chip  316  to be measured by an external measuring apparatus.  
      It is possible to detect the presence, for example, of ALT that is one of the hepatic enzyme at the fraction portion  235  of chip  316 . For example, if a sample consisting of blood plasma is introduced into inlet  217 , it, will be guided only to the fraction portions  235  whose flow control channels  314  are kept open. If one of those fraction portions  235  whose flow control channels  314  are kept open is allowed to contain in advance a measurement reagent  236  comprising, for example, L-alanine, α-ketoglutaric acid, β-reduced nicotinamideadeninedinucleotide (NADH), L-lactatedehydrogenase (LDH), and so on, a coloring reaction represented by: 
 
NADH—&gt;NAD + 
 
 will occur at the fraction portion  235  which will be detected by the measuring apparatus  237 . The ALT activity is determined based on the altered transmittance of light having a wavelength of 340 nm passing through the fraction portion  235  and detected by the measuring apparatus  237 . To eliminate the contribution of non-specific absorption, dual wavelength measurement including the measurement at the wavelength of 405 nm may be performed. 
 
     Third Embodiment  
      The chip described in relation to the first and second embodiments may further include a separation unit for separating specified components of a sample before the sample is subjected to analysis (detection or measurement), at an intermediate stage between the sample sample introduction unit  212  and the flow control unit  312 .  FIGS. 19 and 20  are block diagrams for representing the functional components of chips representing this embodiment of the invention. The chips  324  and  325  shown in  FIGS. 19 and 20  respectively further include a separation unit  213  between sample introduction unit  212  and flow control unit  312  and makes it possible to perform analysis (detection or measurement) on the component separated in advance from a sample. Description will be given below taking as an example a chip including a detection unit  214 , which serves as an analysis unit ( FIG. 19 ).  
       FIG. 21  is a diagram for representing the components of an exemplary chip further including a separation unit  213 . The chip  326  shown in  FIG. 21  is similar in its basic structure to the chip  313  shown in  FIG. 2  except that it includes between sample inlet  217  and dispensing channels  222  a separation region  218 , which contains part of main channel  221 . The chip  326  further includes, in addition to the components of the chip shown in  FIG. 2 , a waste reservoir  219 , a buffer inlet  220 , and a channel  230 . The number of detection reservoirs  223  may be determined as appropriate.  
      The separation region  218  includes the channel  230 , main channel  221 , and plural thin channels  229  connecting them, and acts like a filter. In communication with the channel  230  there is provided the waste reservoir  219  for the disposal of waste. In communication with the main channel  221  there is provided the buffer inlet  220 . With the exemplary chip  326  shown in  FIG. 21 , the separation region  218  acts like a filter. However, the operation style of separation region  218  is not limited to the above, but may include many variations.  
       FIG. 22  illustrates the structure of separation region  218 . Referring to  FIG. 22 , there are formed on a substrate  216  channel grooves  161   a  and  161   b  (each having a width W and depth D) with a partition wall  165  in between. Either one of the channel grooves  161   a  and  161   b  serves as main channel  221  and the other as channel  230 . Across the partition wall  165  there are formed separation channels at regular intervals. The term “separation channel” used herein represents each of the thin channels  229 . The separation channels each having a width of d 1  cross at right angles with channel grooves  161   a  and  161   b , and are arranged with a constant interval of d 2  between adjacent separation channels. The dimensions of the components shown in the figure may be altered as appropriate depending on the type of samples to be separated, and, for example, appropriate values may be chosen from the ranges cited below.  
      W: 10 μm to 1000 μm  
      L: 10 μm to 1000 μm  
      D: 50 nm to 1000 μm  
      d 1 : 10 nm to 10 μm  
      d 2 : 10 nm to 100 μm  
      Out of the above dimensions, the value L defining the length of separation channel must be precisely determined according to the analysis purpose because it directly affects the separation ability. For example, if separation of a polymer is required, the polymer will undergo conformational change during its passage through a separation channel that will cause the change of enthalpy. The overall change of enthalpy a polymer undergoes during its passage through a separation channel varies depending on the length of the separation channel. Thus, from the viewpoint of separation channel, its length affects the separation ability of the separation channel. In the invention, since the channels consist of grooves, it is possible to form them by etching or molding while precisely controlling their shape and size. As a result it is possible to stably produce a separation device having a specified separation ability. Formation of channel grooves  161   a  and  161   b , and separation channels may be achieved by any appropriate method, but is preferably practiced by dry etching in combination with electron beam exposure, particular when the separation channel is designed to have a depth d 1  and interval d 2  of 100 nm or less.  
      Separation of molecules occurring at the separation region  218  shown in  FIG. 22  will be described with reference to  FIG. 23 .  FIG. 23  is a top view of the separation device for showing the outline of the structure thereof. First, before separating components from a sample, a buffer serving as a carrier is allowed to flow through the channel grooves. Referring to  FIG. 23 , an original sample containing a mixture  150  of different components flows from up downward in the figure through channel groove  161   b . Then, smaller molecules  151  of the mixture pass through separation channels provided to the partition shown at the center of the figure and enter into the adjacent channel groove  161   a . Through the channel groove  161   a  there flows from down upward in the figure a solvent that is chosen so as not to react with the molecules to be separated. Hence, the smaller molecules  151  entering the channel groove  161   a  move upward in the figure being carried by the flow of solvent. On the other hand, larger molecules  152  flowing along channel groove  161   b  cannot pass through the separation channels, and keep flowing in the same direction along the channel groove  161   b . Thus, smaller molecules  151  are separated from larger molecules  152 .  
      In the separation unit shown in  FIG. 22 , currents flowing along the channel grooves  161   a  and  161   b  are opposite to each other. But, the two currents may flow in the same direction. Use of two currents flowing in the opposite directions, however, will improve the separation efficiency of the unit. For example, the current flowing along channel groove  161   a  may be allowed to flow from up downward instead of from down upward. Then, a concentration of smaller molecules  151  becomes higher with its passage through the separation path. Thus, the concentration of smaller molecules  151  in the current flowing along channel groove  161   a  approaches the counterpart in the channel groove  161   b  until the former equals to the latter at certain point. Ahead of the point, migration of larger molecules  152  through separation channels will rarely occur, thus incapacitating the separation of larger molecules  152 . In contrast, when the two currents flow in the opposite directions as in the present embodiment, the difference in concentration of larger molecules  152  between the two currents flowing along channel grooves  161   a  and  161   b  is maintained, and thus the high separation ability of the unit is ensured even when the separation channel has a certain large length.  
      In the above embodiment, plural thin channels  229  which serve as separation channels are formed through the partition wall. The separation region  218  may include a bank portion as in an embodiment described below.  
       FIG. 45  shows another configuration of the separation region  218 . separated Figs. A and B show its sectional and perspective views respectively. As shown in  FIG. 45A , on a substrate  216  there are formed two parallel channel grooves  161   a  and  161   b  with a partition wall  308  between the two grooves. The partition wall  308  is in the form of a bank. A lid  226  is placed over the substrate  166 . In  FIG. 45B , the lid  226  is not represented for the convenience of illustration.  
      As seen from  FIG. 45A , a blank space exists between the summit of partition wall  308  and the lid  226 , and thus the two channel grooves  161   a  and  161   b  communicate with each other through the blank space. This blank space corresponds to the separation channels formed through the partition wall  165  of separation region  218  described above. Thus, it is possible to practice separation operation by flowing a sample containing a substance to be separated along channel groove  161   a , and a buffer along channel groove  161   b.    
      In this case, the lid  226  is preferably made of a hydrophobic material such as polydimethylsiloxane, polycarbonate and so on. By so doing it becomes possible to reliably introduce sample and buffer into their respective channel grooves without taking the risk of cross-contamination between the two, and to allow the two solutions to contact with each other via the blank space at a time when the two channel grooves are filled with sample and buffer. The same advantage will be ensured by lacking the lid  226 , because then air will act as a hydrophobic substance, and perform the same task as does the lid  226 .  
      Let&#39;s assume that the separation unit has a lid  226  made of a hydrophilic material such as polyethylene terephthalate. If a sample is passed through, for example, channel groove  161   a , part of the sample will move to the other channel groove  161   b . During the movement of sample, only the molecules whose size is smaller than the blank space formed between the partition wall  308  and the lid  226  will be allowed to selectively pass through the space. Thus, separation of smaller molecules can be achieved.  
      According to this embodiment, by providing the partition wall  308 , since one current flowing along channel groove  161   a  and the other current flowing along channel groove  161   a  allowed to contact with other, separation of target molecules occur at a larger extent than is possible with the above embodiment where separation of target molecules occur at thin separation passages  229  formed at a part of partition wall  165 , which will improve the efficiency of separation. If the molecules have a slender contour, they will easily pass through the space without being captured there. Thus, the unit can be profitably used for the analysis of a sample that contains molecules having such a complex shape.  
      Formation of channel grooves  161   a  and  161   b  with a partition wall  308  in between may be achieved by processing a (100) Si substrate using wet etching. When a (100) Si substrate is used, a groove with a trapezoidal profile as shown in the figure will be formed by etching in a direction in parallel with or normal to (001) direction. It will be thus possible to determine the height of partition wall  308  by adjusting the etching time.  
      The partition wall  308  may be formed on the lid  226  as shown in  FIG. 46 . It is possible to readily obtain a lid  226  with a partition wall  308  by subjecting a resin such as polystyrene to injection molding. On the other hand, it is possible to obtain the substrate  216  by forming a single passage groove on a substrate  216  by etching. Since it is possible to process the separation region  218  by simple procedures as described above, the chip is suitable for mass production.  
      As seen from above, by attaching a separation region  218  to part of main channel  221 , it is possible to separate the introduction of liquid sample into the system via capillary action and the separation of target components via diffusion. Separation of target molecules may occur via their difference in osmotic pressure.  
      Turn back again to  FIG. 21 . A sample, after being introduced into inlet  217 , is guided via capillary action to channel  230 . When the channel  230  is filled with the sample, a predetermined buffer is introduced via the buffer inlet  220 . The buffer is used as a mobile phase for separating components contained in the sample. Buffer, after being introduced into buffer inlet  220 , is guided via capillary action to main channel  221 , and flows in a direction opposite to the direction in which sample in the channel  230  flows.  
      Since thin channels  229  connecting channel  230  and main channel  221  have a smaller width or depth than the channel  230 , in the channel  230  only the molecules having predetermined size and shape can pass through the thin passages  229  to reach the main channel  221  to merge the current there. The molecules which cannot enter the thin channels  229  are evacuated into the waste reservoir  219 . Thus, the molecules of a sample can be separated according to a size or a shape they take in the mobile phase. The thin channels  229  may be substituted for tiny orifices formed on a thin partition separating channel  230  and main channel  221 .  
      Introduction of such a separation region  218  will make it possible to subject a sample to coarse separation or refined purification. By subjecting a sample to coarse separation, it is possible to remove the sample of solid objects, cells and so on. If a sample is liquid, it is possible to separate low molecular weight components from high molecular weight components.  
      Sample components flowing through the main channel  221  are distributed to the dispensing channels  222  communicating with the main channel  221  to be guided to the respective detection reservoirs  223  for dispensing. For the chip  326  as in the chip  313  shown in  FIG. 2 , the sample is distributed only to the detection reservoirs  223  which are connected to the dispensing channels  222  whose flow control units  314  are kept open.  
      In the embodiment, since flow control units  314  of dispensing channels  222  with their detection reservoirs  223  are provided downstream of separation region  218 , it is possible to perform detection or measurement operation on the component having undergone separation operation secondary to the introduction of sample via inlet  217 , in accordance with the parameters required for a given test. Thus, it is possible to customize the configuration of the chip  326  by setting an opening and closing the flow control channels  314  connected to respective dispensing channels  222 . According to the embodiment, since target components in a sample are separated in advance prior to analysis, it is possible to perform high sensitivity detection operation at the detection reservoir  223 .  
      For example, it is possible to determine the concentration of sugar in blood at a detection reservoir  223  of a chip  326 . In this case, when a blood sample is introduced via an inlet  217 , red cells are separated out at the separation region  218 . The plasma component is then diluted with buffer introduced via a buffer inlet  220  and guided to the detection reservoir  223 . A detection reagent  231  including NAD (β-oxidized nicotinamide adenine dinucleotide), ATP (adenosine triphosphate sodium), hexokinase, glucose-6-phosphatedehydrogenase, and magnesium acetate is put in advance in the detection reservoir  223 . The coloring reaction occurs at the detection reservoir  223 . Then, the blood sugar level of the sample can be easily determined by measuring the intensity of coloration.  
      The present embodiment may further include a mixing portion between the separation unit  213  and analysis unit (detection unit  214  or measurement unit  233 ) to enhance the homogenous mixture of sample before the sample is subjected to detection or measurement. Explanation will be given below with reference to a chip including a detection unit  214 .  FIG. 24  shows the configuration of an exemplary chip having a mixing portion  248 . The chip  327  shown in  FIG. 24  is similar in its basic structure to the chip  326  shown in  FIG. 21  except that it includes a mixing portion  248  at a section of main channel  221  between separation region  218  and dispensing channels  222 .  
      The mixing portion  248  of the chip  327  is not limited to any specific shape and structure, as long as it can homogenize the sample flowing through the main channel  221 , but may take, for example, the following structure.  
       FIG. 25  shows an exemplary configuration of the mixing portion  248 . The mixing portion  248  shown in  FIG. 25  consists of an entrance passage including a current and counter current to enhance the vigorous agitation of flow therethrough. The entrance passage includes a forward passage  252  and backward passage  253  both forming the segments of main channel  221 , and tiny passages for mixing  254  connecting the two passages. The tiny passages for mixing  254  may be substituted, for example, for tiny orifices formed on a partition separating the forward passage  252  from the backward passage  253 .  
      The surfaces of fine channel for mixing  254  are preferably more hydrophobic than those of forward passage  252 , because then current will not move from forward passage  252  through the fine channel for mixing  254  to backward passage  253  until the forward passage  252  is filled with liquid flowing from the separation region  218 . When the forward passage  252  is filled with the liquid, and the liquid reaches the head portion of backward passage  253 , into the fine channel for mixing  254  one fraction of liquid enters from backward passage  253  and another fraction of liquid enters from forward passage  252 , and the two fractions of liquid collide in the fine channel for mixing  254  where dispersion of elements to opposite liquid masses occurs which contributes to the homogenization of liquid. The thus homogenized liquid flows along main channel  221  to be distributed via dispensing channels  222  to their respective detection reservoirs  223 .  
      Thus, it is possible to homogenize the concentration of a liquid reaching dispensing channels  222  after having passed the backward passage  253 . Accordingly, even if the density of sample components contained in the liquid having passed the separation region  218  is uneven, it is possible to provide fractional liquids where the density of a sample component is homogenized to selected detection reservoirs  223 , which will elevate the precision of detection of reaction occurring at the detection well.  
      Let&#39;s assume, for example, that a front part of a liquid mass has a higher density of sample components. As the liquid mass moves from main channel  221  to forward passage  252 , its front part intermingles with the inflow of liquid from backward passage  253  which has been sufficiently mixed to have a comparatively homogeneous density, and thus the front part comes to have a more even density of components with progression of the liquid mass through the mixing portion. Then, let&#39;s assume the contrary case in which a tail part of a liquid mass has a higher density of sample components. The liquid mass moves from main channel  221  to forward passage  252 . It occurs at a certain time that when the front part of liquid mass runs backward passage  253 , its tail part moves still along forward passage  252 . Then, its front part having a lower density of components intermingles with the inflow of liquid from the tail part having a higher density of components, which will homogenize the density of the two parts in question. In the particular embodiment shown in  FIG. 25 , the main channel  221  is in the form of a straight line, but it may take a zigzag line or spiral line. By so doing it is possible to further miniaturize the mixing portion  248 , thereby reducing the overall size of a chip.  
       FIG. 26  shows another configuration of the mixing portion  248 . The mixing portion  248  shown in  FIG. 26  includes a reservoir  255  along the path of main channel  221 , and, downstream of the reservoir  225 , a trigger channel  256  connecting main channel  221  at its two different sites. The trigger channel  256  is a collateral channel connecting two different sites of main channel downstream of the reservoir  255 . It is possible to control the flow velocity of a liquid through the trigger channel  256  by changing the hydrophilic property or the size of the channel as appropriate. This helps to control the speed of switching operation. The trigger channel  256  has two intersections with main channel  221 . The intersection on the downstream side or towards dispensing channels  222  includes a liquid switch portion  257 .  
      With the mixing portion  248  configured as described above, the liquid switch portion  257  is initially closed, and thus liquid from the separation region  218  accumulates in the reservoir  255 , and the conentration of the liquid is homogenized. When the reservoir  255  is filled with liquid, a fraction of the liquid enters into the trigger channel  256 . When the trigger channel  256  is filled with liquid, and the front part of liquid reaches the liquid switch portion  257 , the liquid switch portion  257  is opened, and liquid whose cocentration is homogenized in the reservoir  255  is allowed to flow towards dispensing channels  222 .  
       FIGS. 27A  to  27 C are top views of the liquid switch portion  257  shown in  FIG. 26 . The liquid switch portion  257  is a switch for controlling the movement of liquid, and is opened/closed via the triggering action of liquid movement.  FIG. 27A  depicts the switch closed; and  FIGS. 27B and 27C  the switch opened. In the figure, to the side surface of main channel  221  is connected the trigger channel  256 . It is possible to control the flow velocity of liquid through the trigger channel  256  by changing the hydrophilic property or the diameter of the passage as appropriate. This helps to control the speed of switching operation. Upstream (upward in the figure) of the intersection between main channel  221  and trigger channel  256 , there is provided a damming portion  258 . The damming portion  258  is so constructed as to exert stronger capillary action than other adjacent portion in the channel. As exemplary structures of the damming portion  258 , followings may be mentioned.  
      (i) Structure Constituted of Plural Columnar Bodies  
      The damming portion  258  having this structure has a larger surface area per unit volume than other channels corresponding in size. Therefore, even when the main channel  221  is filled with liquid, the damming portion  258  will have a larger solid-liquid interface than other parts of the channel.  
      (ii) Structure Filled with Porous Particles or Beads  
      The damming portion  258  having this structure will have a larger solid-liquid interface than other part of the channel.  
      (iii) Structure Consisting of Hydrophobic Surfaces  
      The damming portion  258  having this structure will intercept the passage of liquid because of the lyophobic activity of its columnar walls.  
      When the damming portion  258  adopts structure (i), the dimension of the columnar body may be determined according to the shape and material of a substrate. If a substrate made of glass or quartz is used, the columnar bodies may be prepared by photo-lithography or dry etching. If a substrate made of plastic is used, a die is prepared that includes a negative cast of the columnar bodies, and the desired columnar bodies are obtained by molding plastic with the die. Incidentally, such a die as described above can be obtained by photo-lithography or dry etching.  
      When the damming portion  258  adopts structure (ii), that damming portion will be obtained by filling the necessary part of main channel with porous particles or beads, or attaching porous particles or beads by adhering to the walls of the necessary part of main channel.  
      The present embodiment will be described on the premise that the damming portion thereof adopts structure (i).  
       FIG. 28  is a top view of the damming portion  258 . Plural columnar bodies  260  are arranged in an orderly fashion with a constant interval between adjacent columnar bodies. The space left by the columnar bodies  260  constitutes a fine channel  261 . The damming portion  258  having this structure has a larger surface area per unit volume than other chanels corresponding in size. Because of this, liquid reaching the damming portion  258  is prevented from advancing further by the capillary action exerted by the damming portion, and thus it is holded at the fine channel  261 .  
       FIG. 27A  shows the stand-by state of liquid switch portion  257 . At the state, liquid sample  259  having flown along main channel  221  is held at the damming portion  258 . At a desired timing under this state, when a triggering liquid  262  is allowed to pass through the trigger channel  256 , as shown in  FIG. 27B , the front part of liquid mass passing through the triggering liquid  262  comes into contact with the damming portion  258 . Although, under the state shown in  FIG. 27A , the liquid sample  259  is held stationary on account of the capillary action exerted by the damming portion  258 , at the moment when the triggering liquid  262  comes into contact with the liquid sample  259  as shown in  FIG. 27B , the liquid sample  259  moves downstream (downward in the figure) to resume its flow. Namely, the triggering liquid  262  serves as priming water and the function as a liquid switch portion is achieved for urging the downward flow of liquid sample  259 .  
      Both the liquid sample  259  and triggering liquid  262  have passed reservoir  255 . Thus, according to this embodiment, it is possible to prohibit the entry of sample to dispensing channels  222  for the period elapsed while the sample has passed separation region  218 , filled reservoir  255  and reached to the front part of the trigger channel  256 , that is, the intersection of main channel  221  with trigger channel  256 . Since, during the period, homogenization of the concentration by diffusion and the like in reservoir  255  is advanced, it is possible to further enhance the homogenization of the concentration of sample components.  
      The timing at which liquid comes to dispensing channels  222  can be varied by altering the length and shape of trigger channel  256  as appropriate. Thus, it is possible to delay the timing of the entry of liquid to dispensing channels  222  by appropriately adjusting the trigger channel  256 . Or, in other words, the trigger channel  256  can also acts as a delaying channel.  
       FIGS. 29A  to  29 C illustrate the exemplary structures of the trigger channel  256 . The trigger channel  256  shown in  FIG. 29A  has an expanded channel region  263  along the path of trigger channel  256 . The expanded channel region  263  serves as a delaying reservoir of the trigger channel  256  or acts as a delaying channel. Introduction of the expanded channel region can delay the timing at which the liquid switch portion  257  is opened.  
      The trigger channel  256  shown in  FIG. 29B  includes the same expanded channel region  263  with the one shown in  FIG. 29A  except that the region has a hydrophobic region  264 . The hydrophobic region  264  is formed across the expanded channel region  263  in a direction perpendicular to the direction of flow in trigger channel  256 , and this inhibits the flow of liquid along the inner wall of expanded channel region  263 .  
       FIG. 29C  shows a trigger channel  256  in the form of a zigzag line. With such a trigger channel, it is possible to alter the delay time, or to open the liquid switch portion  257  at a desired timing by adjusting the shape and length of the trigger channel  256 . The shape of trigger channel  256  is not limited to the one shown in  FIG. 29C , but may take, for example, a spiral form as long as it is sufficiently small in size.  
      According to the embodiment configured as described above, components are separated from a sample at the separation portion  218 , the density of the components is homogenized at mixing portion  248 , and the resulting liquid is distributed to dispensing channels  222 . Thus, the liquid passed through the separation unit  213  is homogenized and then provided to each detection unit  214 . Thus, it is possible to perform more precise, sensitive detection operation on the reaction for the test items selected by the opening and closing of the flow control units  314 .  
      The trigger channel  256  having a delaying channel may be further modified such that its delaying time can be customized in accordance with a given request. Reaction which is necessary for detection requires a certain time, and mixture of one reagent component with another also requires another definite time. The delaying channel is introduced for ensuring such wait time. The wait time is different for each reaction and each operation. For a chip having a basic structure comprising plural analysis units (detection portions  214  or measurement units  233 ) to achieve plural analyses procedure different from each other, it is desirable to include a delaying channel that allows the setting of any desired delay time in accordance with the test. If the delaying channel described below is incorporated in the embodiment or other embodiments in the specification, it will be possible for those embodiments to set the wait time of delaying channel in accordance with the requirement from a given test.  
       FIGS. 47A and 47B , and  FIGS. 48A and 48B  are top views for showing the structure of delaying channel capable of setting a desired delay time. The delaying channels shown in  FIGS. 47A and 47B  represent the modifications of the expanded channel regions  263  shown in  FIGS. 29A and 29B  of trigger channel  256 .  
      The delaying channel shown in  FIGS. 47A and 47B  include, as its basic structure, an inflow channel  800 , an outflow channel  801 , and an expanded channel region  802 . To customize the delaying channel shown in  FIGS. 47A and 47B  such that it gives a desired delay time, it is necessary to adjust the position of an interrupter for customizing  803 . Formation of the interrupter for customizing  803  may be achieved by pressing a heater as depicted in  FIG. 41  to an appropriate position of expanded channel region to deform a thermoplastic material there into a bulge that will act as an obstacle to the flow through the region. It is possible to obtain a desired delay time by changing the position of heater unit, thereby shifting the position of the interrupter for customizing  803  as appropriate.  
      Formation of the interrupter for customizing  803  may be achieved by pressing a stamp having a hydrophobic PDMS rubber pad or by applying hydrophobic ink onto an appropriate position of expanded channel region, thereby forming a hydrophobic coat there.  
      Protruding region of the interrupter for customizing  803  shown in  FIG. 47A  into the expanded channel region  802  is rather short, and thus current from inflow channel  800  can take a short course to reach outflow channel  801 , which allows the current to pass the expanded channel region  802  in a short period. In contrast, when interrupter  803  protrudes more heavily towards the expanded channel region  802  as shown in  FIG. 47B , current from inflow channel  800  must take a longer course to reach outflow channel  801 , which causes the current to take a longer time to pass the expanded channel region  802 . Thus, it is possible to customize in advance the delay time in accordance with a given test by adjusting the position of the interrupter for customizing  803 . The number of the interrupter for customizing  803  is not limited to any specific one. For example, it is possible to lengthen the maximum delay time by providing two or more the interrupter for customizing  803  arranged in parallel within the expanded channel region  802 .  
       FIGS. 48A and 48B  show a different kind of delaying channel which alters the delay time by changing the length of channel. The delaying channel shown in  FIGS. 48A and 48B  includes an inflow channel  810 , an outflow channel  811 , and two extended connectors  812  connecting the two. When it is required to obtain a delaying channel with a desired delay time, a customizing channel  813  is formed between the two extended connectors  812  at an appropriately chosen level. Formation of a customizing channel  813  may be achieved by cutting a groove connecting the two extended connectors  812  using a thin, microscopic abrasion machine like the one used for dicing. The cutting edge of microscopic abrasion machine is so sharp that the notch of extended connector  812  coincides well with the profile of the customizing channel  813 .  
      The customizing channel  813  may be a bridge made of a highly hydrophilic substance such as carboxymethylcellulose gel or agarose gel, which is placed between the two extended connectors  812 . Since aqueous solution can move such a hydrophilic bridge by wetting it, the connection will be established between the two extended flow passages. Formation of such a bridge may be achieved by stamping a hydrophilic gel between the two passages, or by printing a sol form between the two passages to be dried later.  
      The customizing channel  813  shown in  FIG. 48A  is formed at a position far apart from the extended connector  812 . In this case, current must flow a long distance as shown by the dotted line in the figure, thus lengthening the delay time. In contrast, the customizing channel  813  shown in  FIG. 48B  is formed close to the extended connector  812 . Thus, the path for current to take for passing from inflow channel  810  to outflow channel  811  becomes short which reduces the delay time. Thus, it is possible to customize the delay time in accordance with a given test by forming a customizing channel  813  at an appropriate position using an abrasion cutter. Incidentally, for the delaying passage shown in  FIGS. 48A and 48B , the two extended connectors  812  run parallel to each other with blind ends at their terminals. However, they may be in communication with each other at their distal ends. In short, they may take any form, as long as the form does not interfere with the function of customizing channel  813 .  
      The above explanation has been given on the premise that the trigger channel  256  also includes a lag channel as shown in  FIGS. 47A and 47B , and in  FIGS. 48A and 48B . The embodiments shown in the figures can be attached to any specified channel or trigger channel of any chip described in the embodiment and other embodiments in the specification, and thereby make it possible to customize the delay time in accordance with a given test.  
      The basic structure of liquid switch portion of a chip representing the present embodiment can also be incorporated in the embodiments described below.  
     Fourth Embodiments  
      The chip described in relation to the first to third embodiments may further include a pretreatment unit for applying specified pretreatment on a sample before the sample is subjected to separation, at an intermediate stage between the sample introduction unit  212  and the separation unit  213  and the pretreatment unit can further include a flow control unit  314 .  FIGS. 30 and 31  are block diagrams for representing the functional components of chips representing this embodiment of the invention. The chips shown in  FIGS. 30 and 31  include detection unit  214  and measurement unit  233  respectively as analysis unit. Both the chips  329  and  330  shown in  FIGS. 30 and 31  include a pretreatment unit  266  between sample introduction unit  212  and separation unit  213 . Description will be given below taking as an example a chip including a detection unit  214  like the one shown in  FIG. 30 .  
       FIG. 32  is a diagram for representing the components of an exemplary chip that can be used as a chip  329 . The chip  331  shown in  FIG. 32  includes a pretreatment unit  266  with a control portion between inlet  217  and separation region  218 . Pretreatment performed at pretreatment unit  266  may include the dissolution of extracellular components (for example, collagen), or reduction of the viscosity of a thick sample (for example, saliva or nasal secretion) to improve the fluidity of the sample.  
       FIG. 33  is an enlarged view of the pretreatment unit  266  shown in  FIG. 32 . The pretreatment unit  266  includes a channel  300  in communication with main channel  221 ; a pretreatment reservoir  269  provided along the channel  300 ; channels  332  and  333  in communication with pretreatment reservoir  269 ; reagent reservoirs  301  and  302  in communication with channels  301  and  302  respectively; a trigger channel  334  branched from the main channel  221  at the downstream side of the channel  330  and in communicating with the channel  332 ; a trigger channel  256  which is branched from the trigger channel  334  at the branching portion  336 , providing an expanded channel region  263  as the time delaying reservoir thereto, interflowing to the main channel  221  via the liquid channel portion  257  at the downstream side of trigger channel  334 , and provided the expanded channel region  263  thereto.  
      The pretreatment unit  266  further includes flow control units  314   p ,  314   q ,  314   r , and  314   s  on the passage  300 , trigger channel  334  upstream of the branching potion  336 , trigger channel  334  at downstream of the branching portion  336 , and trigger channel  335 , respectively. Each of the pretreatment reservoir  269 , the reagent reservoir  301 , the reagent reservoir  302 , trigger channel  256 , trigger channel  334  and trigger channel  335  is provided with a vent hole  225 .  
      Since the pretreatment unit  266  includes flow control units  314   p  and  314   q , it can perform pretreatment operation at a pretreatment reservoir  269  at a single step or two separate steps. Or if it is required to do so, the pretreatment unit  266  can omit the execution of pretreatment.  
      (a) Pretreatment at Pretreatment Reservoir  269  is not Executed  
      The flow control units  314   p  and  314   q  of pretreatment unit  266  should be closed. The structure of flow control units  314   p  and  314   q  may be the same as that of the corresponding flow control portion of the first embodiment. When flow control units  314   p  and  314   q  are closed, sample flowing through main channel  221  cannot advance to the pretreatment reservoir  269  or to channel  332 . The sample will pass by the pretreatment unit  266  leaving it alone.  
      Sample is blocked at the liquid switch portion  257  provided on main channel  221 . Alternatively, some part of sample enters trigger channel  256  from main channel  221  and moves along the circuit to reach the liquid switch portion  257 . At that moment, the liquid switch portion  257  is opened in the manner as described in relation to the third embodiment. Thus, the sample restarts to flow along main channel  221  towards the separation region  218 . In this case, the expanded channel region  263  may be set to give a minimum delay, or the trigger channel  256 , the liquid switch portion  257 , the expanded channel region  263 , and the liquid switch portion  257  may be omitted in acvance.  
      (b) One Step Pretreatment is Executed at Pretreatment Reservoir  269   
      In this case, flow control unit  314   p  on channel  300 , and flow control units  314   q  and  314   r  are opened, and flow control unit  314   s  is closed.  
      Since flow control unit  314   p  on channel  300  is open, a sample introduced via inlet  217  into the system runs past main channel  221  and channel  300  to enter pretreatment reservoir  269 . The pretreatment reservoir  269  is a well for applying specified pretreatment to sample introduced via inlet  217 . The pretreatment reservoir  269  may include in advance a reagent (not shown) necessary for pretreatment such as an enzyme, for example, collagenase, lysozyme chloride and so on. If the pretreatment consists of certain operation such as incubation, introduction of a pretreatment reagent is not necessary.  
      The reagent reservoir  301  may include the same volume of buffer with the capacity of pretreatment reservoir  269 . Sample, after having undergone pretreatment at pretreatment reservoir  269 , must flow back to main channel  221 . For this purpose, the level of liquid in the reagent reservoir  301  should be maintained as high as or higher than the liquid in the main channel  221 .  
      The liquid switch portion  257  provided between pretreatment reservoir  269  and reagent reservoir  301  allows reagent reservoir  301  to hold buffer by taking the structure shown in  FIG. 53  which will be described later.  
      When a pretreatment reagent is introduced into pretreatment reservoir  269 , it reacts with a reagent put in advance to produce a specified pretreatment reaction. Incidentally, a part of the sample move from the pretreatment reservoir  269  to the channels  332  and  333 , and is dammed at the liquid switch portions  257  provided to the channels  332  and  333 , respectively.  
      Part of reagent moves along channel  300 , past main line  221 , enters trigger channel  334  on the channel connecting the pretreatment reservoir  269  and the reagent reservoir  301 , and reaches liquid switch portion  257  to open it. Then, buffer in the reagent reservoir  301  flows upstream towards pretreatment reservoir  269  and pushes the content of pretreatment reservoir  269  towards main channel  221 . The delay time the trigger channel  334  requires for opening the liquid switch portion  257  is adjusted to be longer than the time required for pretreatment reaction. For this purpose, an expanded channel region may additionally be introduced into the loop of the trigger channel  334 .  
      One other part of reagent enters from main channel  221  into the trigger channel  256  and reaches liquid switch portion  257 . When the sample in trigger channel  256  reaches the liquid switch portion  257 , the liquid switch portion  257  opens, and thus sample in main channel  221  starts to flow again towards separation region  218 . The trigger channel  256 , expanded channel region  263 , and liquid switch portion  257  are provided to close main channel  221  until sample has been pretreated sufficiently in pretreatment reservoir  269 . The delay time introduced by expanded channel region  263  should be adjusted to be sufficiently long as to allow the pretreatment reservoir  269  to be filled with sample.  
      (c) Two Step Pretreatment is Executed at Pretreatment Reservoir  269   
      Two step pretreatment may include, for example, a first step of decomposing extracellular substances such as collagen to allow thereby cells (for example, insulin cells, glucagon cells) in a sample (for example, tissue such as Langerhans&#39; islands) to deposit at the base of reaction reservoir, and a second step of applying a chemical agent (for example, glucose) to the precipitated cells, recovering the product (for example, insulin) secreted by the cells as a result of reaction, and transporting the product to main channel.  
      In this case, flow control unit  314   p  on channel  300 , and flow control units  314   q ,  314   r  and  314   s  are opened. The pretreatment reservoir  269  may include in advance a reagent (for example, freeze-dried collagenase) as needed. The reagent reservoir  301  may also include a reagent or a buffer (for example, glucose solution) necessary for the second step reaction. The reagent reservoir  302  may include buffer that pushes back the sample having undergone reaction towards the main channel. The level of liquid in the first and reagent reservoirs  301  and  302  should be maintained as high as or higher than the liquid in the main channel  221 . The reagent reservoirs  301  and  302  may include a volume of buffer as large as or larger than the capacity of pretreatment reservoir  269 .  
      Sample introduced via inlet  217  enters the pretreatment reservoir  269  to fill it. Then the first step reaction (for example, exposure of cells as a result of the dissolution of collagen and deposition of cells) occurs. The sample advances further along main channel  221  and a part of the sample turns aside to enter trigger channel  334 . After a sufficiently long delay for the completion of first step reaction which is generated by the sample running along the trigger channel  334 , the liquid switch portion  257  between pretreatment reservoir  269  and reagent reservoir  301  is opened. Then, a reagent (for example, glucose solution) necessary for the second step reaction and stored in reagent reservoir  301  moves to pretreatment reservoir  269 , and pushes out the liquid resting in pretreatment reservoir  269  to displace the liquid there completely. The liquid pushed into main channel flows upstream along main channel because the liquid switch portion  257  provided to a downstream point of main channel is still closed.  
      After a sufficiently long delay for the completion of second step reaction (for example, reaction in which insulin cells produce insulin as a response to glucose solution), the liquid switch portion  257  between pretreatment reservoir  269  and reagent reservoir  302  is opened. Then, buffer stored in the reagent reservoir  302  pushes out the content (for example, glucose solution containing insulin produced by cells) of pretreatment reservoir  269 , and transports the content as a new sample to main channel  221 .  
      Another part of sample enters from main channel  221  into trigger channel  256  and runs along the latter to reach liquid switch portion  257 . When the sample in the trigger channel  256  reaches the liquid switch portion  257 , the liquid switch portion  257  opens, and the sample having undergone pretreatment advances towards separation region  218 .  
      As seen from above, it is possible according to the chip of the invention to allow the first and second step reactions to occur dependent on the configuration of the chip itself without requiring any external control unit for the purpose.  
     Fifth Embodiment  
      The chip described in relation to the above embodiments may further include a reaction unit  275  between the separation unit  213  and the flow control unit  312 , and the reaction unit may further include a flow control unit  314 .  FIGS. 34 and 35  are block diagrams for representing the functional components of chips representing this embodiment of the invention. The chips shown in  FIGS. 34 and 35  include detection unit  214  and measurement unit  233  respectively as analysis unit. Both the chips  337  and  338  shown in  FIGS. 34 and 35  include a reaction unit  275  between separation unit  213  and flow control unit  312 .  
      Description will be given below taking as an example a cofiguration corresponding to the chip  337  shown in  FIG. 34 .  FIG. 36  is a diagram for representing the components of an exemplary chip that corresponds to a chip  337 . The chip  339  shown in  FIG. 36  includes a reaction unit  275  between separation portion  218  on main channel  221  and dispensing channels  222 .  FIG. 37  illustrates the configuration of reaction unit  275  shown in  FIG. 36 . The reaction unit  275  shown in  FIG. 37  is similar in its basic structure to the pretreatment unit  266  shown in  FIG. 33  except that it includes a reaction reservoir  340  instead of a pretreatment reservoir  269 .  
      The reaction reservoir  340  shown in  FIG. 37  is a well for allowing an element contained in sample and separated at the separation region  218  to undergo a specified reaction. Like the pretreatment unit  266  described in relation to the fourth embodiment, the reaction unit  275  includes flow control units  314   p ,  314   q ,  314   r , and  314   s . It is possible to achieve, at the reaction unit  275  like the foregoing pretreatment portion, no reaction, one-step reaction or two-step reaction by setting an opening and closing the flow control portions appropriately. Exemplary one step reactions may include solubilization of cells, mixing of reagents and so on, while exemplary two step reactions may include recovery of a product secreted by cells such as insulin or the like. The treatment step is similar to that observed with the pretreatment unit  266 .  
      For one step pretreatment to be executed at reaction portion, flow control unit  314   p  on reaction unit  275 , and flow control units  314   q  and  314   r  are opened, and flow control unit  314   s  is closed. The reaction reservoir  340  may include in advance a surfactant for solubilizing the membrane of cells which is constituted of lipids membrane, and freeze-frozen lipase for decomposing lipids, while a reagent reservoir  301  may contain buffer.  
      The reaction unit  275  may further includes another separation region  218 . Then, sample having undergone reaction is transported to the separation region  218  downstream of the reaction reservoir  340  where further separation is executed. Then, if sample having undergone solubilization reaction still contains some insoluble molecules, those insoluble molecules will be eliminated during the passage of the sample through the separation region  218  provided downstream of reaction reservoir  340 .  
      The above explanation has been given on the premise that the reaction unit  275  includes the reagent wells  301 ,  302  connected in series. However, the reaction unit  275  may include three or more reagent reservoirs. The above exemplary chip includes a single reaction unit  275 . However, the chip may include two or more reaction portions  275 .  
     Sixth Embodiment  
      The chip described above in relation to the foregoing embodiments may include an analysis unit (detection unit  214  or measurement unit  233 ) connected to a reservoir where a flow control unit  312  is provided to the connecting channel. With a chip having a configuration as described above, it is possible to select any desired one among one step reaction to multi-step reaction as appropriate in accordance with the requirement from a given test. The configuration of analysis portion can be varied so as to allow any typical reactions to occur to meet any general-purpose applications as will be described later in relation of an eighth embodiment. If a number of such general-purpose analysis portions different in their property are combined on a chip, the chip will command profitably wide applicability.  
      Description will be given below taking as an example a detection unit  214  that allows predetermined-step(s) reaction to occur. Description will be given below with reference to figures about a detection unit  214  having a single detection reservoir  223 . However, as described later with reference to  FIG. 38 , the detection unit  214  may include two or more detection reservoirs  223  and peripheral members.  
       FIG. 49  illustrates the configuration of a detection unit  214 . The detection unit  214  shown in  FIG. 49  is similar in its basic structure to the pretreatment unit  266  shown in  FIG. 33  except that it includes a detection reservoir  223  instead of a pretreatment reservoir  269 .  
      The detection reservoir  223  shown in  FIG. 49  is a well for allowing an component of a sample introduced via inlet  217  to undergo a specified detection reaction. Like the pretreatment unit  266  described in relation to the fourth embodiment, the detection unit  214  includes a flow control unit  314 . It is possible to achieve, at the detection unit  214 , one step reaction to two step reaction by setting an opening and closing of the flow control unit  314  appropriately, or to omit such reaction altogether.  
      Sample having undergone separation operation at separation region  218  enters detection reservoir  223  as needed, and undergoes specified reaction. Downstream of the detection reservoir  223 , there is provided a liquid switch portion  257 , and thus downstream movement of liquid in detection reservoir  223  beyond the liquid switch portion  257  is prohibited. It is possible to alter the layout of trigger channel  256  so as to give a delay sufficiently long to allow the detection reaction occurring at detection reservoir  223  to be completed. If the detection reaction takes a long time, the expanded channel region  263  may be enlarged. It is also possible for the trigger channel  256  to include a lag channel thereby altering the delay time to any desired length of time.  
      The above explanation has been given with respect to  FIG. 49  on the premise that the detection reservoir  223  includes reagent reservoirs  301 ,  302  connected in series. However, the detection reservoir  223  may include a single reagent reservoir  301 , or three or more reagent reservoirs.  
       FIG. 58  shows a variation of the detection unit shown in  FIG. 49  in which the detection reservoir includes a single reagent reservoir  301 . For detection reaction to occur at the detection reservoir  223  shown in  FIG. 58 , it is necessary to open flow control units  314   p  and  314   q . In contrast, to prohibit detection reaction at detection reservoir  223 , it is necessary to close flow control units  314   p  and  314   q.    
      The detection portion shown in  FIG. 58  includes a closing switch  640  between flow control unit  314   p  on the passage  300  and the detection reservoir  223 .  FIG. 52  is a top view for showing the structure of the closing switch  640  provided to the detection portion. The closing switch  640  is provided for preventing the upstream flow of sample having undergone reaction from the reservoirs towards main channel  221 . The closing switch  640  includes an expanded portion  641  provided to the channel and a bulging body  642  embedded in the expanded portion. When liquid passes through the channel  607  and the expanded portion  641 , the bulging body  642  bulges slowly as a result of the interaction with the liquid until it completely occludes the expanded portion  641  that enables the delayed occlusion of the channel  607 .  
      Suitable materials for the bulging body  642  may include dried and contracted polyacrylamide, beads consisting of a water-absorbing polymer. The bulging body  642  is stabilized in the expanded portion  641  due to its diameter being larger than that of the channel  607 , adhesion to part of the expanded portion  641  and so on.  
      Turn back again to  FIG. 58 . It is possible to simplify the structure of the system by allowing a detection reservoir  223  to have a single reagent well  301 . For example, a chip where one-step detection reaction is allowed to occur may have such a simplified structure. About the detection portion shown in  FIG. 58 , description has been given on the premise that the detection unit includes two of the flow control units  314   p ,  314   q , one is on the channel  300  and the other is on the trigger channel  334 . However, it is only necessary to provide at least the flow control unit  314   p . It is possible to more reliably inhibit the wasteful consumption of sample by providing flow control unit  314   q  to trigger channel  334 .  
      For example, the detection unit  214  may include five reservoirs. These reservoirs are used as detection reservoir, waste reservoir, reagent reservoir, buffer reservoir and so on, according to the kind of detection reactions.  FIG. 50  is a plane view for showing the configuration of another detection unit  635 . The detection unit  635  shown in  FIG. 50  includes a reservoir group consisting of five reservoirs  630 ,  631 ,  632 ,  633  and  634 ; a channel  607  connecting the reservoir group to main channel  221 ; a liquid switch portion group consisting of four liquid switch portions  623 ,  624 ,  625  and  626 ; an assembly of trigger channels consisting of the trigger channels  620 ,  621  and  622  connecting the liquid switch portion group to the main channel  221 ; lag channels  610  and  611  provided to the trigger channels; and flow control portions  600 ,  601  and  602  responsible for the opening and closing of channel  607  and trigger channels.  
      The detection unit may further include, although it is not absolutely necessary, a trigger channel  256 , an expanded channel region  263 , and a liquid switch portion  257 , in order to close main channel  221  until sample fills the reservoir  630 .  
      Each of the five reservoirs  630 ,  631 ,  632 ,  633  and  634  and the reservoir  635  has a vent hole  225 . The reservoir  630  is mainly used as a detection reservoir. The reservoirs  631  and  632  are mainly used for storing waste. The reservoirs  633  and  634  are mainly used as reagent reservoirs for supplying reagent to reservoir  630 .  
      To main channel  221 , there are provided from upstream downward in order a bifurcation for trigger channel  256 , bifurcation for channel  607 , bifurcation for trigger up-loop circuit  620 , and bifurcation (that is to say, liquid switch  257 ) for the downstream limb of trigger channel  256 .  
      To the stem channel  607  bifurcating from main channel  221  there are provided from upstream downward in order a flow control portion  600 , closing switch  640 , bifurcation for first limb channel  607 , reservoir  630 , liquid switch portion  623 , reservoir  631 , liquid switch portion  624 , and reservoir  632 . To one second limb channel  607  bifurcated from first limb detection passage, there are provided from upstream in order a liquid switch portion  625  and reservoir  633 . To other second limb detection passage bifurcated from first limb detection passage, there are provided from upstream in order a liquid switch portion  626  and reservoir  634 .  
      The trigger channel  620  includes from upstream downward in order a flow control unit  601  and a lag channel  610 , and bifurcates at a downstream end to produce a trigger channel  621  and another trigger channel  622 . To the trigger channel  621  there are provided from upstream downward in order a liquid switch portion  623  and another liquid switch portion  625 . The distal end of the trigger channel  621  communicate with a vent hole  225 . To the trigger channel  622  there are provided from upstream downward in order a flow control portion  602 , lag channel  611 , liquid switch portion  624 , and liquid switch portion  626 . The distal end of trigger limb  622  communicates with another vent hole  225 .  
       FIGS. 51A  to  51 C are sectional views for showing the structure of a chip having a detection unit  635  as depicted in  FIG. 50 .  FIGS. 51A  to  51 C show the cross-sections of the detection portion cut along line X-X′ of  FIG. 50 . The chip whose cross-sections are shown in  FIGS. 51A  to  51 C includes a substrate  701  and a lid  700 . All the channel systems formed on the substrate  701  have the same depth with that of main channel  221  excepting vent holes  225 . The lid  700  has vent holes  225  so as to communicate with the reaction reservoirs. Reagents necessary for detection reactions are distributed to the reservoirs  630  to  634  formed on the substrate  701 , and flow control portions  600 ,  601  and  602 , and delay time of a lag channel  610 ,  611 ,  612  are adjusted in accordance with a given test (customized). Then, the lid  700  is joined to the substrate  701 .  
      With the chip shown in  FIG. 51A , reservoirs  630  to  634  have the same depth with that of main channel  221 . Since liquid is driven via capillary action promoted by the hydrophilic property of the channels, driving force is given even if they have the same depth.  
      If difference in water level is utilized in addition to capillary action, it will be possible to move liquid more speedily.  FIG. 51B  shows the cross-section of a chip in which water-level difference is also utilized. To utilize water-level difference, four kinds of channels are prepared that have four different depths ranked as the shallowest level zero to the deepest level 3. In the particular example shown in the figure, the main channel  221 , the trigger channel group and the lag channel group have a depth of level zero; the reservoir  630  has a depth of level 1; and the reservoirs  631  and  632  which mainly serve as waste reservoirs have a depth of level 2 and 3, respectively. Because of the difference in depth, water-level difference is produced between different kinds of reservoirs after the reservoirs are filled with liquid as a result of capillary action. Particularly force driving liquid from the main channel  221  to the reservoir  632  is produced. Although not shown in the figure, the reagent reservoirs  633  and  634  used for supplying the reagents are formed to have a depth of level zero.  
      With the chip shown in  FIG. 51B , the reservoir has a different volume according to its depth. It is possible to equalize the volumes of all reservoirs, thereby ensuring the economic use of reagents necessary for measurement.  FIG. 51C  is a modification of the chip shown in  FIG. 51B . With the chip of  FIG. 51C , reservoirs  630 ,  631  and  632  have the same volume. The substrate of the chip shown in  FIG. 51C  has a stacked structure comprising four thin substrates  702  and one common substrate  701 . Through-holes are formed at appropriate positions on each thin substrate  702 , and then they are joined to allow the through-holes to be put together to form thereby some of the reservoir group, assembly of channel  607 , trigger channel group, the vent holes  225 . Although not shown in  FIG. 51C , the trigger channel group has a depth of level zero as does the vent hole  225 , but after forming a liquid switch portion it extends downward to communicate with a reservoir. To the top surface of chip, a lid  700  having vent holes  225  formed is joined as shown in  FIG. 51B .  
      As noted above, suitable materials of a chip include transparent materials, for example, resins such as PET or PMMA, quartz, glass, and so on. To utilize capillary effect for the transportation of liquid, the interior of liquid transporting channel system is preferably made of a hydrophilic material. If the interior of the channel is made of a hydrophobic material such as PMMA, it is preferable to treat the channel with a surface treatment agent such as MPC or acrylamide gel to apply coating there, thereby to hydrophilize for providing with the higher hydrophilicity. For the liquid switch portion and the like that has a hydrophobic surface, hydrophobic treatment may be applied to the channel surface having be hydrophilized.  
       FIG. 53  gives a top view for showing the basic structure of the liquid switch portions  623  to  626  of detection unit  635  shown in  FIG. 50 . As shown in  FIG. 53 , each of liquid switch portions  623  to  626  includes a channel  607 , a trigger channel  651 , a damming portion  650 , and vent hole  652  provided to the distal end of the trigger channel  651 . The vent hole  652  corresponds to vent hole  225  of  FIG. 50 . The trigger channel  651  corresponds to trigger channel  621  or  622  of  FIG. 50 .  
      The liquid switch portion shown in  FIG. 53  is different from the corresponding switch portion described above in relation to the foregoing embodiments in that damming portions  650  are arranged on both sides of trigger channel  651 . Since two damming portions  650  are arranged on both sides of trigger channel  651 , it is possible to prevent from liquid in trigger channel  651  from entering into channel  607 , even when no liquid is present in channel  607 . If one limb of channel  607  is filled with liquid and the other limb is empty, the liquid in the former limb will not invade the latter because of damming portions  650 . However, as soon as the trigger channel  651  is filled with liquid, the two limbs of channel  607  will communicate with each other as in the above-described liquid switch portions.  
      It is possible to allow any of single to multi-step detection reactions to occur at detection unit  214  by using the chip shown in FIGS.  50  to  53 . Even if the chip includes a measurement unit  233  instead of a detection unit  214 , it is possible to allow sample to undergo any of single to multi-step reactions before measurement by constructing the separation portions in the manner as described above. Practice of clinical biochemical test using the chip as shown in FIGS.  50  to  53  will be described in relation to an eighth embodiment.  
      In the above description, attention has been paid to detection reaction occurring at a single detection reservoir  223  to explain the function of detecting portion  214 . Next, an embodiment where the detection unit  214  includes three detection reservoirs  223  will be described. However, the number of detection reservoirs  223  is not limited to any specific number, and may be two or four or more.  
       FIG. 38  shows the configuration of a detection unit  214  of this embodiment. The detection unit  214  includes from downstream to upward in order three dispensing channels  222   a ,  222   b ,  222   c  which are in communication with detection reservoirs  223   a ,  223   b ,  223   c , respectively. The dispensing channels  222   a  to  222   c  have respective flow control units  314   a  to  314   c , respectively.  
      To a detection reservoir  223   a  are connected a reagent reservoir  301   a  via a channel  332   a , and a second reagent reservoir  302   a  via a channel  333   a . Similarly, to a detection reservoir  223   b  are connected a reagent reservoir  301   b  via a channel  332   b , and a second reagent reservoir  302   b  via a channel  333   b . To a detection reservoir  223   c  are connected a reagent reservoir  301   c  via a channel  332   c , and a second reagent reservoir  302   c  via a channel  333   c.    
      A trigger channel  334  branches off at a point of main channel  221  downstream of dispensing channel  222   a . Trigger channel  334  has a flow control unit  314   d . Trigger passage  334  branches off downstream of flow control unit  314  to produce trigger channel  334   a  connects via a liquid switch portion  257  to the channel  332   a , and a trigger channel  335   a  connects via a liquid switch portion  257  to the channel  333   a . The trigger channel  334  connects via the liquid switch portion  257  to the channel  332   c . Trigger channel  335   a  branches off from trigger channel  334   a . Trigger channel  334   a  has flow control unit  314   e  downstream of the bifurcation point of the trigger channel  335   a . Sub-passage  335   a  has a expanded channel region  263  and a flow control unit  314   f.    
      The trigger channel  334   b  branches off from trigger channel  334  at a point downstream of the foregoing branching off point from which sub-passage  334   a  branches off. The trigger channel  334   b  shoots out a trigger channel  335   b . The trigger channel  334   b  has one flow control unit  314   g  upstream of the bifurcation point of the trigger channel  335   b , and another flow control unit  314   h  downstream of the bifurcation point. The trigger  335   b  has an expanded channel region  263  and a flow control unit  314   i . Trigger channel  334   b  connects via the liquid switch portion  257  to the channel  332   b . The trigger channel  335   b  connects via another liquid switch portion  257  to the connector channel  333   b.    
      From stem-passage  334 , sub-passage  335   c  branches off at a point downstream of the point where sub-passage  334   b  branches off. Stem-passage  334  has flow control unit  314   j  between the two branching-off points: one for sub-passage  334   b  and the other for sub-passage  335   c . Stem-passage has another flow control unit  314   k  at a point downstream of the point where sub-passage  335   c  branches off. Sub-passage  335   c  has expanded channel region  263  and flow control unit  314   l . Stem-passage  334  connects via liquid switch portion  257  to connector channel  332   c . Sub-passage  335   c  connects via another liquid switch portion  257  to connector channel  333   c.    
      According to the configuration of detecting portion  214  shown in  FIG. 38 , it is possible to alter the number of active detection reservoirs as appropriate by opening/closing flow control units  314   a  to  314   l . It is also possible to determine whether a given detection reservoir gives one step reaction or two step reaction.  
      Table 1 shows the layout of flow control portions required for the activation of detection reservoirs  223   a  to  223   c . The table shows the open/closure condition of the individual flow control units  314   a  to  314   l  for each of the detection reservoirs  223   a  to  223   c , which depends on the usage of the reagent reservoirs  301   a  to  301   c  and the reagent reservoirs  302   a  to  302   c . In Table 1, as for the detection reservoirs  223   a  to  223   c , the reagent reservoirs  301   a  to  301   c  and the reagent reservoirs  302   a  to  302   c , a reservoir marked by open circle (‘∘’) is to be used while a reservoir marked by cross (‘x’) is not to be used. Also, as for the flow control portions  314   a  to  314   l , a flow control portion marked by open circle (‘∘’) is to be open while a flow control portion marked by cross (‘x’) is to be closed. In the table, the blank portion for the flow control units indicates that the opening and closing state thereof is variable in accordance with the state of use for other detection reservoirs and the reservoirs.  
      Table 1 
                                                                   TABLE 1                                   314a   314b   314c   314d   314e   314f   314g   314h   314i   314j   314k   314l                                                                                                223a◯   301a◯   302a◯   ◯           ◯   ◯   ◯                               223a◯   301a◯   302aX   ◯           ◯   ◯   X       223a◯   301aX   302a◯   ◯           ◯   X   ◯       223a◯   301aX   302aX   ◯           ◯   X   X       223aX   301aX   302aX   X           ◯   X   X       223b◯   301b◯   302b◯       ◯       ◯           ◯   ◯   ◯       223b◯   301b◯   302bX       ◯       ◯           ◯   ◯   X       223b◯   301bX   302b◯       ◯       ◯           ◯   X   ◯       223b◯   301bX   302bX       ◯       ◯           ◯   X   X       223bX   301bX   302bX       X       ◯           X   X   X       223c◯   301c◯   302c◯           ◯   ◯                       ◯   ◯   ◯       223c◯   301c◯   302cX           ◯   ◯                       ◯   ◯   X       223c◯   301cX   302c◯           ◯   ◯                       ◯   X   ◯       223c◯   301cX   302cX           ◯   ◯                       ◯   X   X       223cX   301cX   302cX           X   ◯                       X   X   X                 DETECTION RESERVOIRS AND RESERVOIRS            OPEN CIRCLE: OPEN            CLOSS: CLOSED            FLOW CONTROL UNITS            OPEN CIRCLE: USED            CLOSS: NOT USED            NO MARK: DEPENDS ON THE USE CONDITION OF OTHER DETECTION RESERVOIRS             
 
      For example, it is possible to determine the level of insulin in plasma by utilizing multi-step reaction at a detection unit  214 . Explanation will be given on the premise that only detection reservoir  223   a  is used for this purpose. To activate only detection reservoir  223   a , flow control units  314   a ,  314   d ,  314   e  and  314   f  are opened. On the other hand, flow control units  314   b ,  314   c  and  314   g - 314   l  are closed.  
      Anti-insulin antibody which serves as a primary antibody is immobilized in advance on the surface of detection reservoir  223   a . Liquid containing anti-insulin antibody to which an enzyme for coloring reaction (“enzyme-linked antibody” hereinafter) is attached is stored in reagent well  301   a . Liquid containing a reagent which develops color under the influence of the enzyme is stored in reagent well  302   a.    
      On the chip prepared as described above, a sample is allowed to flow along the main channel  221 . The sample is guided to the detection reservoir  223   a . Part of the sample enters into the trigger channel  334  at a point downstream of a branching point to detection reservoir  223   a . The sample entering trigger channel  334  takes a certain time to reach via the trigger channel  334   a  to open the liquid switch portion  257 . During this time, the sample is allowed to contact with the liquid in detection reservoir  223   a  where insulin in the sample interacts specifically with anti-insulin antibody immobilized on the surface of the detection reservoir  223   a.    
      As noted above, a part of the sample enters trigger channel  334  and reaches the liquid switch portion  257  at the predetermined time. Then, the liquid switch portion  257  is opened, and enzyme-linked antibody stored in reagent reservoir  301  moves to detection reservoir  233   a . The surface level of liquid in the reagent reservoir  301  is preferably kept higher than that of the detection reservoir  223   a . Then, conveniently a reagent in the reagent reservoir  301  will flow towards the detection reservoir  223   a , as soon as the liquid switch portion  257  on trigger channel  334   a  is opened.  
      Part of sample flowing along trigger channel  334   a  also enters trigger channel  335   a , and, being further delayed during the channel through expanded channel region  263 , reaches the liquid switch portion  257  on the trigger channel  235   a . Then, the liquid switch portion  257  is opened, a coloring reagent stored in the reagent reservoir  302   a  will flow along the channel  333   a  to the detection reservoir  223   a . The surface level of liquid in reagent reservoir  302   a  also is preferably kept higher than that of detection reservoir  223   a.    
      Of enzyme-linked antibodies supplied to detection reservoir  223   a , excess antibodies which did not bind to primary antibodies are pushed out with inflow of the coloring reagent solution towards dispensing channel  222 . On the other hand, coloring reaction expected to occur at detection reservoir  223   a  takes a longer time than the removal of unreacted antibodies from detection reservoir  223   a . Thus, it is possible to remove excess antibodies by using the coloring reagent without requiring deliberate use of cleaning buffer subsequent to the introduction of secondary antibodies. This reduces the necessary number of reagent reservoirs.  
      According to this embodiment, like the pretreatment unit  266  representing the fourth embodiment described above, the liquid levels of the detection reservoirs  223   a  to  223   c , a series of reagent the reservoirs  301   a  to  301   c , and another series of reagent the reservoirs  302   a  to  302   c  may adjusted as appropriate so that movement of reagents towards detection unit  214  smoothly occurs via capillary action. Through this arrangement, it is possible to simplify the structure of chip without requiring the use of an external driving unit.  
      According to the aforementioned configuration, plural reservoirs communicate with each other in detection unit  214 , and the connections between reservoirs are altered via the open/closure of flow control units  314  provided to each connector channel. Therefore, it is possible to detect insulin dependent on the coloring reaction of sample by sequentially operation in the detection unit  214 .  
     Seventh Embodiment  
      The chips in the above embodiments will be beneficially used for biochemical test. Description will be given below about the chip on the premise that the chip is used for biochemical test in which the hepatic function is evaluated based on subject&#39;s blood sample.  
      The basic structure of the chip may be similar to that of the third embodiment. The detection unit  214  may include detection reservoirs  223  sufficiently to determine, for example, the test items listed in Table 2. The items listed in Table 2 can be determined via single step reactions by supplying in advance appropriate reagents to detection reservoirs  223 . If a detection reservoir  223  is connected to a reagent reservoir, a flow control unit  314  attached to the channel connecting them should be closed.  
      Before using a chip for a test, the tester selects test items to be determined if necessary from the items listed in Table 2. If the tester wants to evaluate the hepatic function of a patient, he selects the items marked by open circle (‘∘’) in the column titled “Hepatic function set.” If the tester wants to evaluate the renal function of a patient, he selects the items marked by open circle (‘∘’) in the column titled “Renal function set.” In addition to aforementioned items, other items may be selected as needed. Then, the tester opens the flow control units  314  on the dispensing channels  222  leading to the detection reservoirs  223  assigned to the detection of selected items, while he closes the flow control units  314  on the dispensing channels  222  leading to the detection reservoirs  223  assigned to the detection of not-selected items. Thus, he can readily customize the configuration of the chip in accordance with the test items.  
      Table 2 
                           TABLE 2                           HEPATIC   RENAL           ITEM   FUNCTION SET   FUNCTION SET   MEASUREMENT METHOD                  TOTAL PROTEIN           BIURET METHOD       ALBUMIN           BCG METHOD       DIRECT-REACTING BILIRUBIN           ENZYME(BOX) METHOD       AST(ASPARTATE AMINOTRANSFER-   ◯       JSCC - BASED AST ASSAY       ASE)       ALT(ALANINE AMINOTRANSFERASE)   ◯       IFCC METHOD       LDH(LACTODEHYDROGENASE)   ◯       CELLULOSE ACETATE MEMBRANE-EASED                   ELECTROPHORESIS &amp; JSCC-BASEO LDH ASSAY       γ-GTP   ◯       JSCC-BASED γ-GTP ASSAY       ALP(ALKALINE PHOSPHATASE)           BESSEY-LOWRY METHOD       BUN(BLOOD UREA NITOROGEN)       ◯   UREASE/INDOPHENOL METHOD       CREATININE       ◯   ENZYME(POD)METHOD       AMYLASE           GS-CNP SUBSTRATE METHOD       TOTAL CHOLESTEROL           ENZYME (CHOLESTEROL ESTERASE OXIDASE(MET         LDL-CHOLESTEROL           JSCC-BASED LDL-CHOLESTEROL ASSAY                  
 
     Eighth Embodiment  
      In this embodiment, steps required for the execution of clinical biochemical test will be described with reference to the analysis portion described in relation to the sixth embodiment (FIGS.  50  to  53 ). The chip shown in FIGS.  50  to  53  has the detection unit  635  as analysis unit, but the following explanation will also apply to a chip having a measurement unit as analysis unit.  
      The chip is a general-purpose chip having an analysis unit as shown in FIGS.  50  to  53  which allows one to apply various detection reactions by opening/closing the flow control portions provided therein.  
      Reactions used for the clinical biochemical test can be classified according to the number of reaction steps into one-step reactions, two-step reactions and three-step reactions. Among typical test method used in the clinical biochemical test, colorimetry, enzyme method, UV method, latex agglutination method (LA method), latex agglutination turbidity immunoassay (LATIA assay), turbidity immunoassay (TIA assay), and selective inhibition belong basically to one-step reactions. Even if an pretreatment step is involved, they can complete in two steps. Radio immunoassay (RIA), chemical luminescence assay (CLIA), chemical luminescence enzyme-linked immunoassay (CLEIA), enzyme-linked immunosorbent immunoassay (ELISA) can basically complete in three steps.  
      One-step to three-step reactions will be described below with reference to the analysis portion shown in FIGS.  50  to  53 . However, four or more or multi-step reactions will be achieved in the same manner as in one-step to three-step reactions using the present chip, by only increasing the number of the reservoirs and the liquid switch portions provided to detection unit  635 .  
      Practice of one-step reaction will be described first. One-step reaction is a reaction obtained by mixing a sample with a reagent directly. One-step reaction is allowed to occur at detection unit  635  (such type of detection unit is called as class 1 detection unit) shown in  FIG. 50  where flow control unit  601  is closed. For one-step reaction, reservoir  630  is used for detection reservoir. A reagent necessary for the reaction is introduced in advance in reservoir  630  in accordance with a kind of a substance to be detected and the measurement method. After the reagent is applied, a lid  700  may be joined to the chip.  
      The reagent may include coloring reagent which react with the substance to be detected to give a color or dye for coloring reaction as in the quantification of albumin. As for the enzyme method, the reagent may be an enzyme which use a substance to be detected to give a color, and the like. As for the UV method, the reagent may be substrate, or co-enzyme (NAD + /NADH or NADP + /NADPH) for the reaction of the enzyme being a substance to be detected. As for the latex agglutination method or the latex agglutination turbidity immunoassay, the reagent may be suspension of latex beads on which antibodies against a substance to be detected are immobilized. As for the turbidity immunoassay, the reagent may be antibody solution, the antibody being against a substance to be detected. These reagents are set at the appropriate volume ratio to the sample. A suitable reagent for a given reaction may be determined by referring to a textbook (for example, see Kanai, I. (author), Kanai, M. (ed.), “Handbook of Clinical Laboratory Test,” Revised 31st Edition, Kanehara Publishing).  
      When sample flows along main channel  221  and reaches the branching portion of channel  607  connected to reservoir  630 , it reaches reservoir  630  to fill it since flow control portion  600  is open. However, since the channel  607  connecting reservoir  630  to reservoir  631  is closed at liquid switch portion  623 , entry of sample to reservoir  630  is stopped when sample fills reservoir  630 . A bulged body  642  can be made of the material which close down the channel after the reservoir  630  is sufficiently filled, so as to prevent the countercurrent of sample to the main channel  221  during reaction. Sample encounters reagent in reservoir  630  to evoke detection reaction. The smaller the capacity of reservoir  630  is, the faster the sample intermingles with reagent. The other part of sample advances further along main channel  221 , but cannot enter trigger channel  620  because flow control unit  601  is closed. Thus, liquid switch portion  623  is kept closed.  
      When the reaction involves coloration or enzyme reaction, sample is exposed to reagent for a specified time. Then, the absorption in reservoir  630  is measured, by using the reservoir  630  as an optical cell. For example, a light is irradiated with over lid  700  and the transmitted light is received by a photosensitive unit placed beneath substrate  701 . As for UV method, determination of the consumption of coenzyme (NAD + /NADH or NADP + /NADPH) by UV (ultraviolet ray) proceeds in the same manner. The absorption of UV by the reaction system is followed at regular intervals, and the activity of enzyme to be detected is determined based on the consumption speed of enzyme. When UV method is used, substrate  700  and lid  700  are preferably made of quartz because it transports UV light well.  
      When latex agglutination (LA) method is used, latex beads are allowed to mix with sample, and left to deposit on the bottom of reaction reserboir. Then, the absorption of light in the reservoir  630  is measured. For latex agglutination method, the reservoir  630  preferably has a conical or semi-circular bottom. If sample does not contain any reactive agent, individual beads will not agglutinate but simply precipitate as separate particles and concentrate to the summit of cone or semi-circle, which enhances the transmission of light. If sample contains reactive agent, beads agglutinate together to form aggregates that adhere to the bottom surface. Thus, beads spread over the bottom that lowers the transmission of light. Thus, it is possible to determine whether sample contains a target reactive substance or not by measuring the transmittance of reservoir  630 .  
      When latex agglutination turbidity immunoassay (LATIA) is used, the turbidity of reaction system is measured at regular intervals, without waiting to occur precipitation, thereby monitoring how fast the turbidity increases as a result of agglutination. Based on the result, it is possible to quantify a target substance. According to turbidity immunoassay (TIA), change of the turbidity due to aggregates of substances in a sample and the antibody is measured.  
      Next, description will be given about how two-step reaction is allowed to occur at reaction portion. Two-step reaction is used for a step for pre-treating a substance that is used for reagent for the later one-step reaction. For two-step reaction, a detection unit  635  (such type detection unit will be called as class 2 detection unit hereinafter) is employed in which, according to  FIG. 50 , flow control portions  600  and  601  are opened, and flow control portion  602  is closed. With class 2 detection unit  635 , reservoir  631  instead of reservoir  630  is used for measurement. Into reservoir  631  is introduced a reagent as used in one-step reaction. Into reservoir  630  is introduced a reagent necessary for pretreatment: if pretreatment involves the prohibition of re-coagulation, at least one chosen from heparin, EDTA and citric acid in the form of dry powder is introduced. The reservoir  633  is kept empty.  
      The procedures necessary for allowing sample to enter via flow control portion  600  to reservoir  630  are similar to those observed in class 1 detection unit. With class 2 detection unit, since flow control unit  601  is open, a sample passes along lag channel  610  and advances through trigger channels  620  and  621  to reach the liquid switch portion  623  and open it. The delay time determined by lag channel  610  is so chosen as to allow sample and reagent to be mixed well in reservoir  630 . When liquid switch portion  623  becomes open, communication between reservoir  630  and  631  is established, sample having undergone pretreatment enters reservoir  631  via capillary action or supported by water-level difference. There, sample intermingles with reagent at reservoir  631 . Since flow control portion  602  is closed, liquid switch portion  624  is not opened. Liquid flowing into reservoir  631  stays there. The reaction in reservoir  631  is subjected to measurement.  
      Next, description will be given about how three-step reaction is allowed to occur at reaction portion. For three-step reaction, a detection unit  635  (such type detection unit  635  will be called as class 3 detection portion hereinafter) is employed in which, according to  FIG. 50 , all flow control portions  600 ,  601 ,  602  are opened.  
      When class 3 reaction unit is used for immunological reaction detected by radio immunoassay (RIA), an antibody against a target substance is immobilized in advance to the inner surface of reservoir  630 . Into reservoir  633 , a radio-labeled standard solution is introduced, while into reservoir  634 , an emulsified scintillation solution which transforms radioactive energy into light energy is introduced. Immobilization of antibody to the surface of reservoir  630  may be achieved physically by spontaneous adsorption to the clean surface of the material, or chemically by using a coupling agent having amino or carboxyl group.  
      The procedures necessary for allowing sample to enter from main channel  221  to reach reservoir  630  are similar to those observed in class 1 detection portion. Then, a target substance in sample bind to antibody immobilized on the surface of reservoir  630 . In contrast with class 1 reaction unit, however, since flow control portions  601  and  602  are open, part of sample passes along lag channel  610  and trigger channels  620  and  621  to open liquid switch portions  623 ,  625  sequentially. Thus, communication is established between reservoir  630  and reservoir  631 , and part of sample is evacuated into reservoir  631  that is used as waste reservoir. The delay time determined by lag channel  610  is so chosen as to allow sample and antibody to sufficiently interact each other in reservoir  630 . When liquid switch portion  625  is opened, radioactive standard solution stored in reservoir  633  passes via channel  607  to reservoir  630 , and pushes out sample staying at reservoir  630  towards reservoir  631 , and fills reservoir  630 . These sequential flows terminate when reservoir  631  is filled. At this stage, in reservoir  630 , radioactive standard substance in solution and a specific substance in sample compete for binding to antibody. The more the content of specific substance in sample is, the less the radioactive standard substance bound to antibody is.  
      Sample, passing along lag channel  612 , opens liquid switch portions  624 ,  626  sequentially, liquid in reservoir  631  flows towards reservoir  632  while emulsified scintillator solution stored in reservoir  634  passes along channel  607  and pushes liquid in reservoir  630  towards reservoir  631 ,  632 . The delay time determined by lag channel  611  is so chosen as to allow reaction between specific substance in sample and antibody to reach equilibrium.  
      These sequential flows terminate when reservoir  631  is filled. At this stage, reservoir  630  is filled with emulsified scintillator solution. The less the content of specific substance in sample is, the more the radioactive standard substance bound to antibody is. The emulsified scintillator solution filling reservoir  630  emits light in the darkness, being activated by the radioactive standard substance. The energy of light is counted by a photo-counter. Based on the result, it is possible to estimate the content of the specific substance in the sample.  
      When class 3 detection unit  635  is used for immunological reaction detected by chemical luminescence immunoassay (CLIA), an antibody specific for a target substance is immobilized in advance to the inner surface of reservoir  630 . Into reservoir  633 , a solution with luminescent antibody is introduced. The luminescent antibody is obtained by attaching chemical luminescent substance (acridinium ester or the like) to the antibody specific to a target substance. Into reservoir  634 , buffer for washing is introduced.  
      Sample is allowed to fill reservoir  630  via the same procedures as for one-step reaction, and react with antibody there until liquid switch portions  623  and  625  are sequentially opened. The delay time determined by lag channel  610  is so chosen as to allow a target substance and antibody to react fully. As soon as liquid switch portion  625  is opened, luminescent antibody solution stored in reservoir  633  enters via channel  607  into reservoir  630  to wash out liquid there towards reservoir  631 . The inflow of luminescent antibody solution terminates filling reservoir  630  when reservoir  631  is filled with the solution.  
      Sample passes along lag channel  612 , and liquid switch portions  624 ,  626  are opened sequentially. Then, liquid in reservoir  631  flows towards reservoir  632 , and then washing buffer stored in reservoir  634  flows along channel  607  and washes out the content of reservoir  630  towards reservoir  632 . The delay time determined by lag channel  611  is so chosen as to allow a target substance and luminescent antibody to bind together fully. These sequential flows terminate when reservoir  632  is filled. At this stage, reservoir  630  is filled with washing buffer. The higher the concentration of specific substance in sample in reservoir  630  is, the more the luminescent antibody binds to the substance. Thus, it is possible to estimate the concentration of the specific substance in sample by measuring the intensity of luminescence.  
      Chemical luminescence enzyme-linked immunoassay (CLEIA) can be also employed by using class 3 detection unit  635  according to the same procedures used in chemical luminescence immunoassay (CLIA). Instead of antibody specific to a target substance coupled with chemical luminescent substrate, antibody against the target substance and coupled with an enzyme that react with luminescent substrate to develop color is set in reservoir  633 , and instead of washing buffer, luminescent substrate solution is set in reservoir  633 , so the measurement can be employed as the same procedures used in CLIA.  
      When class 3 detection unit  635  is used for immunological reaction detected by enzyme immunoassay (EIA), the same procedures as used in chemical luminescence immunoassay (CLISA) may be employed. Instead of antibody against the target substance and coupled with an enzyme that react with luminescent substrate, a solution of an antibody against the target substance and to which an enzyme such as peroxidase is linked is prepared wherein the enzyme will develop color as a result of reaction with its substrate. Into reservoir  634 , a die solution responsible for the development of color instead of substrate solution is introduced. The remaining procedures are the same with those for CLEIA.  
      For the three-step reactions described above, washing occurs at single step. However, the more the number of washing is, the higher the precision of measurement is. Thus, if it is required to improve the precision of measurement by increasing multiple-step washing, it is only necessary to add a desired number of sets of reservoir, lag channels, trigger channels, and liquid switch portions.  
      FIGS.  54  to  57  cite lists of principal test items required for an ordinary recheck test, involved methods, and applicable class of reaction unit. From the inspection of FIGS.  54  to  57 , it is obvious that a chip containing class 1, 2 and 3 reaction units can well manage common recheck tests. Namely, it is possible to prepare in advance standardized general-purpose chips which can manage ordinary test items required for a recheck test shown in FIGS.  54  to  57 .  
      For example, based on the list shown in  FIG. 54 , it is possible to prepare a general-purpose chip for the diabetes which includes one or more of the class 1 reaction unit and one of the class 3 reaction unit. With such a chip at hand, it is possible to check the condition of diabetes readily at site. Prior to the test, however, it is necessary to introduce at least one reagent necessary for checking diabetes is introduced into at least one reaction unit. As for the class 1 reaction unit, for example, at least one chosen from hemoglobin A1c, 1,5-anhydro-D-glucitol, and glycoalbumin should be introduced. If it is required to know the activity of enzyme in diabetes, a reagent necessary for assaying anti glutamate decarboxylase antibody should be introduced into a class 3 reaction unit. The reaction units of a chip are not necessarily filled with reagents.  
      With this general purpose chip used for the check of diabetes, it is possible to readily select the appropriate items at site according to the disease condition or history of a patient to be examined. According to the method of the embodiment, it is thus possible by using a general-purpose chip to customize its reaction unit at a post-processing stage to match an individual need.  
      As shown in FIGS.  54  to  57 , general-purpose chips for the diagnosis of obesity, hyperlipidemia, hepatic function disorde, nephrosis, hypertension, adrenal function, gout, thyroid function disorder, anemia (microcytic, macrocytic) can be prepared. For the diagnosis of a disease as mentioned above, it is possible as in diabetes to modify the configuration of a chip according to the disease, and to supply reagents for items described in FIGS.  54  to  57  as appropriate to its reaction units of the appropriate class.  
      The general-purpose chip may be so constructed as to have the same number of analysis units with that used for sample measurement, and may be subjected to the same analysis task using a standard solution instead of the sample. Thus, the measurement further enhanced in the accuracy can be realized based on the general-purpose chip.  
     Ninth Embodiment  
      The chip represented by the above embodiments may be manufactured with a machine as described below.  FIG. 39  shows a schematic diagram for showing an exemplary chip manufacturing system representing this embodiment. The chip manufacturing apparatus  342  shown in  FIG. 39  is an apparatus for producing a chip whose configuration is customized according to a request from a laboratory center. Description will be given below of the system on the premise that the chip manufactured has a detection unit  214  as analysis portion. However, the present system can be applied as well for the manufacture of a chip having a measurement unit  233  as analysis portion.  
      The chip manufacturing apparatus  342  includes a reception unit  343 , selecting unit  346 , chip import unit  349 , chip storage unit  350 , chip stock unit  351 , pre-arrangement treatment unit  352 , reagent import unit  353 , reagent storage unit  354 , reagent arrangement unit  355 , post-arrangement treatment unit  356 , and chip export unit  359 .  
      A substrate  216  is transported via chip import unit  349  to chip storage unit  350  where the substrate  216  is stored. Reagents and buffer necessary for reactions occurring at detection reservoirs  223  are transported via reagent import unit  353  to reagent storage unit  354  where they are stored. The reagent may be stored in the form of beads on which it is carried.  
      Reception section  343  receives input from a laboratory center that will use a chip. Reception section  343  includes item receiving unit  344  and center ID receiving unit  345 . Parameter receiving subsection  344  receives input about information of parameters to be determined with a chip. Center ID receiving unit  345  receives IDs of a test center or a doctor, who are the client for the chip manufacturer.  
      Selection unit  346  selects a substrate  216  and detection reagents based on the information provided by reception unit  343 . Substrate selection unit  347  selects a substrate  216  used for the fabrication of a chip. The selected substrate  216  is transported from substrate storage unit  350  to substrate stock unit  351 . Reagent selection unit  348  selects reagents including detection reagents and buffers to be introduced into detection reservoir  223 , reagent reservoir  301 , reagent reservoir  302 , and other reservoirs. The thus selected reagents are transported from reagent storage unit  354  to reagent arrangement unit  355 .  
      Pre-arrangement treatment unit  352  activates the surface of substrate  216  selected by selecting unit  346  according to the information inputted in the reception unit  343  so that a selected reagent efficiently adsorbs to the surface of substrate  216 . The same section may apply a cover over the substrate for fear that reagents may be blown off from the region to filled with the reagent.  
      Reagent arrangement unit  355  distributes reagents including detection reagents or buffers selected according to required items to detection reservoir  223 , reagent reservoir  301 , detection reservoir  302  and other reservoirs of substrate  216  held at substrate stock unit  351 . If distribution of liquid reagent is required, a certain amount of the reagent may be transferred into a cylinder, and part or all of the cylinder content may be injected to an assigned area. The injected reagent may be exposed to dry air or nitrogen gas to be dried and solidified being deprived of the solvent. If reagent beads are used, a bead having a sufficient size to carry a sufficient amount of reagent as to cause detectable reaction in detection reservoir  223  may be prepared in advance, and such a bead may be supplied to detection reservoir  223 .  
      Post-arrangement treatment unit  356  opens or closes flow control units  314  as appropriate based on the information about the necessary items of a test provided by item receiving unit  344 . Post-arrangement treatment unit  356  has sealing unit  357  and center ID recording unit  358 . Sealing unit  357  applies a seal  227  on the surface of substrate  216 , thereby protecting the surface of substrate  216 . Sealing unit  357  may further seal channels, detection reservoirs  223 , fraction portion  235  or other reservoirs selected for the purpose. Center ID recording unit  358  records the ID of centers that provide information to center ID receiving unit  345 . The ID may be recorded on substrate  216 , or printed on a package of substrate  216 .  
      Substrate stock unit  351  transports the thus prepared chip to chip export unit  359 . The chip may be packed with an air-tight packaging material as needed, and the pack may be filled with inert gas such as nitrogen. The packaging material may be sealed.  
       FIG. 44  shows the procedures for the manufacture of a chip using a chip manufacturing apparatus shown in  FIG. 39 . Referring to  FIG. 44 , reception unit  345  receives input carrying the information about the ID of clinical center and necessary items (S 101 ). Substrate selection subsection  347  selects a substrate according to the information (S 102 ), and selects channels and channels to be activated on the substrate (S 103 ). Reagent selection subsection  348  selects reagents according to the required parameters (S 104 ). The selected substrate is imported (S 105 ). Pre-arrangement treatment section  352  opens/closes flow control portions as appropriate so that sample can flow along selected channels (S 106 ). Reagent arrangement unit  355  introduces required reagents into their assigned sites on the substrate (S 107 ). Then, post-arrangement treatment section performs post-treatment step (S 108 ). The resulting chip is exported (S 109 ).  
      In the above procedures, selection of a substrate at step  102  and selection of reagents at step  104  may be exchanged. Alternatively, selection of a substrate at step  102  may be followed by the renewed import of another substrate, and then by selection of reagents at step  104 .  
      By using the chip manufacturing apparatus  342 , it is possible to readily produce a chip whose configuration is customized in accordance with the items provided to reception unit  343 . Therefore, it is possible to provide chips whose configuration is optimized for individual needs, even if the number of chip users is immense.  
       FIG. 40  shows a schematic diagram for showing an exemplary chip manufacturing system capable of producing chips whose configuration can be customized according to the health conditions of patients who have received clinical tests in a laboratory of a clinical center. The chip manufacturing system  364  shown in  FIG. 40  is basically similar to the system  342  shown in  FIG. 39 , except that the former has medical record ID reception unit  360  instead of center ID reception unit  345 , and medical record ID recording unit  361  instead of center ID recording unit  358 , and that the former additionally includes digitization unit  362  and output delivery unit  363 .  
      Medical record reception subsection  360  receives input about the information of ID data of the patients of hospitals and visitors for receiving laboratory tests. Medical record recording unit  361  records or prints the ID of a patient on a chip or its package.  
      Digitization unit  362  converts the test result obtained via a chip into numerical data, and delivers the data to output delivery unit  363 . Output delivery unit  363  converts the numerical data into graphs and presents the graphs on display.  
      According to the chip manufacturing system  364 , since each chip has the ID of a patient printed thereon, the doctor and the other person engaged in the test can securely identify which patient a given chip represents. Moreover, since digitization unit  362  converts the test result into corresponding numerical data, it is quite easy to add the data to an electronic medical record. Digitization unit  362  may have the same configuration with that of measuring apparatus  237  described above in relation to the second embodiment.  
      For the chip manufacturing system shown in  FIG. 39  or  40 , control of hardware is achieved by a controller.  FIG. 43  shows the organization of such a chip manufacturing apparatus.  
      Referring to  FIG. 43 , input unit corresponds to reception unit of the system shown in  FIG. 39  or  40 , and includes test item input unit and ID input unit. The controller includes a substrate controller, a reagent controller, and a measurement portion controller.  
      Substrate controller controls, based on the information provided by input unit, the selection of substrate and active channels, and operation involved in the import of a selected substrate and its export. The reagent controller controls, based on the information provided by input unit, selection of reagents, and distribution of reagents to specified sites. The measurement portion controller controls, if the apparatus includes a measurement unit in itself, the measurement unit, a calculation unit responsible for the computation of measurement results, and a display for displaying measurement results.  
      Description has been given above on the premise that a chip is manufactured in a chip factory in which a chip is manufactured on receipt of an order. However, the chip may be customized in a clinical center. For example, an operator in the clinical center can customize a chip at the test stage, by opening/closing flow control units.  
      The present invention has been described above with reference to the embodiments. These embodiments are presented just for illustration, and various modifications and variations thereof are easily thinkable. It will be quite obvious for those skilled in the art that those modifications and variations are also included within the scope of the invention.  
      For example, according to the above embodiments, the flow control portions are provided to some channels, and a selected flow control portion(s) is closed, thereby determining flow through other channels. However, the flow control portions which can be opened may be provided to channels. In this case, initially all flow control potions are closed, and after appropriate channels are selected according to the kind of sample or treatment, the flow control portions connected to those channel are selected and are opened so that sample can be guided through desired channels. With the above arrangement, it is still possible to customize a chip according to a kind of the sample or test items.  
      A flow control unit  314  which is initially closed but can be opened later at a desired time may be manufactured by the following method. The flow control unit  314  has its surface hydrophobic at first which leads to the closure of the portion. Later at a desired time, UV light is impinged to the portion to open it. The hydrophobic treatment may be achieved by using silane coupling agent, silicone oil, and the like, or by forming a thin film of PDMS. The material of the organic film is oxidized and decomposed, when exposed to UV light, to turn hydrophilic compound. Thus, at first, the surface of a flow control portion in contact with a channel is treated with an agent as described above to be hydrophobic or water-repellent, then a UV beam concentrated by using a lens system is impinged onto the flow control unit  314  to be opened. Then, the flow control unit  314  is opened.  
      An alternative method uses an organic substance having a low boiling point for closure and IR laser radiation for opening. A suitable substance having a low boiling point includes paraffin. When paraffin is used, a substrate  216  is heated to a temperature close to the melting point of paraffin. Paraffin in the form of a thin rod is contacted to a flow control unit  314  in a short time, thereby attaching softened paraffin to the channel surface. Thus, the flow control unit  314  is closed. Later at a desired time, IR laser beam is irradiated to the flow control unit  314 . Since paraffin absorbs IR ray, it is heated above its melting-point so that it is melted and vaporized. If paraffin is completely eliminated, the flow control unit  314  is opened.  
      In the above embodiments, sample introduction unit  212  includes the single inlet  217 . However, sample introduction unit may comprise plural inlets  217 . By providing the plurality of the inlet  217 , it is possible to perform multiple tests using a single chip, for example, perform tests on different samples collected from a single patient such as blood, saliva, urine, nasal secretion, and the like. It is also possible to perform multiple tests in parallel using a single chip, for example, perform parallel tests on multiple samples of a single kind (for example, blood) collected from many patients. For a chip having plural inlets  217 , it is also possible to insert a flow control unit  314  between sample introduction unit  212  and separation unit  213 . Through this arrangement, it is possible to select the passage of a sample according to the necessity of the separation unit  213 .  
      According to the above embodiments, flow control units  314  are provided to all dispensing channels  222 . However, flow control units  314  may be provided to some of dispensing channels  222 . For example, if a chip has the detection reservoir  223 , the flow control unit  314  may be provided except the detection reservoir which is utilized in every test.  
      The above embodiments have been illustrated on the premise that the general shape of the detection reservoirs and the fraction portions is cylindrical. However, the general shape thererof is not limited to cylinder but may take any desired shape, as long as it can be used for the analysis (detection or measurement) of the content therein. The shape of the detection reservoirs or the fraction portions may be rectangular column such as a quadrangular prism. The reservoirs and fraction portions may not be a diverticular-like shape, but a channel-like shape, as has already been noted referring to  FIG. 9 .  
      What is said above applies not only to the detection reservoirs and the fraction portions but also to other reservoirs. Namely, those reservoirs may take a shape other than the cylinder, as long as the shape ensures a sufficient volume to hold a liquid which is introduced or corrected thereinto For example, the shape of the reservoirs formed on the chip may be a rectangular column or the channel-like shape having the predetermined plane shape. The reservoir which function as a waste reservoir may also take, for example, a form like a zigzag line, like cylinder with protrusions and cavities on its inner surface. A waste reservoir with such surface contour, because of the increase of surface area, can further enhance capillary action, and ensure the reliable recovery of a waste liquid.