Abstract:
This invention relates to array devices and methods for their fabrication. More specifically, the array devices have automatic flow control, probe array configuration, and dynamic chemical or biochemical reaction for rapid chemical or bio-molecule detection.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims priority to U.S. Provisional Patent Applications, Ser. No. 60/474,777 entitled “A Programmable Bio-Microarray,” filed May 31, 2003, and Ser. No. 60/549,336 entitled “Fluidic Adapter for Spot Array,” filed Mar. 3, 2004. 
     
    
     TECHNICAL FIELD  
       [0002]     This invention relates to array devices, the control of fluid flow within those device, and methods for their fabrication.  
       BACKGROUND  
       [0003]     Microarray technology, providing a quick, cost effective, and parallel analysis, has become a powerful and prominent tool for genomic analysis, molecular diagnosis, and drug development. A microarray is essentially an array of spots on a solid substrate with a surface for molecular probe binding. A DNA microarray is typically composed of DNA “probes” that are bound to a solid substrate such as glass. Each spot in the array lattice is deposited many identical probes that are complementary to the gene sample. During hybridization reaction, “target” DNA samples diffuse passively on the substrate surface, when sequences complementary to the probe will anneal and form a DNA duplex. Hybridized targets can then be read using confocal laser scanning and fluorescence detection. There are two major microarray platforms, one built by synthesis of DNA probes on a substrate in situ and glass slides spotted with complementary DNAs (cDNAs) or oligonucleotides.  
         [0004]     The in situ arrays, most commonly GeneChips by Affymetrix of Santa Clara, Calif., are produced by synthesizing oligonucleotides on a glass substrate using photolithographic techniques adapted from the semiconductor industry. Affymetrix produces these preassembled devices for various applications including RNA expression profiling and single nucleotide polymorphism (SNP) detection. Recently, a programmable microarray with light-directed in situ synthesis is introduced. The technology uses a light-modulator matrix, which acts as light valves to control the synthesis of oligonucleotide probes at given positions on the array. This allows any combination of DNA probes to be fabricated on the chip.  
         [0005]     The spotted arrays are basically microscope slides that have cDNAs or oligonucleotides deposited on their surfaces. The surfaces are coated with materials such as poly-L-lysine or aminosilane that help attach the DNA molecule probes. The spots are typically less than 200 μm in diameter. Spotted arrays can be produced by robotic equipment in a lab with contact or ink-jet printing methods.  
         [0006]     In clinics, high-density microarrays can be used to analyze patient samples and save their lives. But such high density is not important. To determine whether a patient has a particular disease, doctors will need to look only at specific DNA mutations—rarely more than 100. For clinical diagnostic purposes, speed and accuracy are far more important than density.  
       SUMMARY  
       [0007]     This invention presents fluidic programmable array devices with structures and methods of on-chip flow control, flexible probe configuration, and dynamic chemical or biochemical reaction. In general, in one aspect, the present invention sets forth a fluidic programmable array device having an elastomeric body, a substrate, a recess, a fluidic channel, and two loading wells.  
         [0008]     Embodiments of the invention may include one or more of the following features. The array device consists of an elastomeric body and a substrate. The body is an adapter with at least a recess, a fluidic channel, and two loading wells. At the bottom of the device body, the substrate is wedged into and adjacent with the bottom of the device body. The recess is a cylinder with a dome. A spot reservoir comprises the recess and a portion of the substrate at the recess. The substrate basically provides a base of the spot reservoir at the recess for chemical or biological probes to be bound or coupled on it. The substrate may be made of a material, such as silicon, glass, and metal that is able to couple chemicals or molecules on it. The substrate may be coated a material such as ploy-L-lysine, aminosilane, and aldehyde, that is able to couple chemicals or molecules on it. The spot reservoir is connected with the fluidic channel. The fluidic channel can be used for delivering probe and sample solution into the spot reservoir separately. In a preferred embodiment, two fluidic channels are built inside the device body; one is a sample fluidic channel; another is a probe fluidic channel. On both ends of the fluidic channels, loading wells are created. One can be an inlet well, another be an outlet. The dome of the spot reservoir will prevent solution residue at the top edge of the reservoir when the fluidic channel and the spot reservoir are flushed. The body is made of liquid elastomeric material, such as polydimethylsiloxane(PDMS), elastomer or silicone rubber with or without optical transparence.  
         [0009]     In a further embodiment of this invention, the array device may consist of more than the one recess to form an array of the spot reservoirs with the substrate and more than the one sample and the one probe fluidic channels to form a fluidic network. The two fluidic channels are intersected at the each spot reservoir. Each spot reservoir is able to be isolated with each other by microvalves pinching the one fluidic channel or all fluidic channels.  
         [0010]     In general, in another aspect, the present invention features a structure in a device body made of elastomeric material to realize the fluidic manipulation. The structure includes a recess and a fluidic channel. The recess having an elongated shape with a cylindrical top is created in the device body for an actuator to approach the fluidic channel. A deformable membrane is formed between a gap of the fluidic channel and the cylindrical top of the recess. In this embodiment, the recess is underneath the fluidic channel, but it can approach the fluidic channel from the top or the sides around the fluidic channel. By activation and non-activation of the actuator the deformable membrane can be pinched or return to its initial form. The fluidic channel, the deformable membrane, and the actuator compose an integrated pinch microvalve.  
         [0011]     One embodiment of a structure to form the pinch microvalve inside the device body comprises the recess, the fluidic channel, the deformable membrane, and a linear motion actuator. The linear motion actuator with a cylindrical tip is inserted into the recess. When the linear motion actuator moves forward or backward, the deformable membrane is pinched or restored, so the fluidic channel is closed or re-opened. Therefore a pinch microvalve is integrated inside the device.  
         [0012]     Varies linear actuators can be used to realize the pinch microvalve. Embodiments of the linear motion actuator are a piezoelectric motion component, a magnetostrictive component, a shape memory alloy, and thermopneumatic motion actuator. The piezoelectric or magnetostrictive motion component can be embedded in a cavity formed by the recess and the substrate. By applying an electric field or a magnetic field, the component exhibit a displacement that pinches the fluidic channel. The thermopneumatic motion actuator can be realized in a cavity filled with a liquid and a build-in microheater. The cavity is formed by the recess and a substrate. The thermopneumatic motion actuator integrated in the device body performs an expansion or contraction at the deformable membrane when a current is applied to the microheater or not. The deformation of the membrane will close or re-open the fluidic channel.  
         [0013]     At one end of the fluidic channel before the loading well, three pinch microvalves align in series along the fluidic channel. When the actuators move forward and backward in a sequence, the fluidic channel is squeezed or re-opened in the sequence, which propels liquid in the loading well moving forward. The pinch microvalves become a three-stage peristaltic pump.  
         [0014]     In general, in another aspect, the invention presents a fluidic programmable array device with an elastomeric body, a spot reservoir, a fluidic channel, and two loading wells for fully automatic flow control, probe configuration, and dynamic chemical or biochemical reaction.  
         [0015]     Embodiments of the invention may include one or more of the following features. The array device consists of an elastomeric body with a spot reservoir inside. The body is an adapter with at least a recess, a fluidic channel, and two loading wells. From the bottom of the device body, a pillar is inlaid into the recess. The top of the pillar with the recess in the body forms a cavity for the spot reservoir. The top of the pillar basically provides a base of the spot reservoir for chemical or biological probes to be coupled on it. A through channel is in the center of the pillar to form a fluidic connecter to delivering a solution from outside of the device into the spot reservoir. The spot reservoir is connected with the fluidic channel. On both ends of the fluidic channel the loading wells are created. One is used as inlet, another as outlet. The body is made of liquid elastomeric material, such as elastomer, PDMS, or silicone rubber with or without optical transparence.  
         [0016]     Another preferred embodiment of this invention is that the spot reservoir comprises a cavity inside the elastomeric body. A channel in the elastomeric body connects to the cavity from outside of the device. A further embodiment is that a substrate is embedded in the cavity of the spot reservoir. On the substrate there is a center hole coincident with the through channel in the elastomeric body for liquid delivering from outside of the device to the spot reservoir. The top surface of the substrate is capable of coupling chemicals or molecules on it.  
         [0017]     In a further embodiment of this invention, the array device may consists of more than the one spot reservoir to form an array of the spot reservoirs and more than the one fluidic channel to form a fluidic network. The spot reservoir along the fluidic channel is connected by the fluidic channel and able to be isolated with each other by the actuator pinching the fluidic channel.  
         [0018]     For spot configuration, the spot reservoir is connected with the probe fluidic channel while the sample fluidic channel is blocked from the spot reservoir by the microvalves along the sample fluidic channel. The probe solution is loaded into the inlet well and propelled through the fluidic channel into the spot reservoir by the micropump at the inlet well. The molecules or chemicals in the probe solution will be bound or coupled onto the surface of the substrate. This reservoir is configured as a sensor spot to detect the corresponding chemical or biological samples. After the spot reservoir is configured, a wash bath solution can be loaded and pumped through the probe channel to wash away the residual probe solution from the spot reservoir to the outlet well.  
         [0019]     For chemical and biological reaction on chip, the probe fluidic channel is disconnected to the spot reservoir by the microvalves along the probe fluidic channel and the sample fluidic channel is connected to it. The sample solution will be pumped to the spot reservoir through the sample fluidic channel by the micropump at the inlet well. A chemical or biological reaction will be occurred between the probe&#39;s chemicals or molecules and the sample&#39;s chemicals or molecules. After that the wash bath solution will be loaded and pumped through the sample channel to flush away the residual sample solution to the outlet well. With laser induced fluorescence or other detection a positive or a negative reaction between the probe and the sample can be detected.  
         [0020]     In general, in another aspect, the invention features a method that includes assembling a mold body and a set of mold components to form a device mold for a device body, casting the device body from the device mold, removing the set of mold components from the device mold and the device body, releasing the device body from the mold body, and assembling the device with the device body and functional components.  
         [0021]     Embodiments of the invention may include one or more of the following features. Casting the device may include pouring or injecting a liquid elastomeric material into the device mold. The mold component may have a shape that is complementary of a structure of the device after the mold component is removed from the device. The mold component may include an elongated mold component having a same dimension and shape as a channel in the device after the mold component is removed from the device.  
         [0022]     The set of mold components may include a first mold component and a second elongated mold component, the first mold component having a shape configured so that a recess is formed in the device when the first mold component is removed from the device, the second elongated mold component having a same dimension and shape as a channel in the device after the second mold component is removed from the device. The first and the second mold component may be spaced at a distance when the device mold is assembled so that a deformable membrane is formed in the device body between the recess and the channel when the first and the second mold component are removed from the device body.  
         [0023]     The set of mold components may include an elongated mold component and a mold component with a dome head. On the dome head there is a slot with a dimension substantially the same as a dimension of the elongated mold component. The mold component with its dome supports the elongated mold component at a predetermined position relative to the mold body when the device mold is assembled. Assembling the device mold may include inserting the elongated mold component into the slot.  
         [0024]     The set of mold components may include a castable mold component having a shape suitable for forming a cavity and an elongated mold component suitable for forming a channel connecting the cavity in the device. On the castable mold component there is a slot with a same dimension and shape as the elongated mold component. The mold body may have a sidewall with a slot at a predefined position relative to the mold body. Assembling the device mold may include inserting the elongated mold component through the slot on the castable mold component and the slot on the sidewall of the device mold. The elongated mold component supports and aligns the castable mold component in the device mold. To embed a substrate inside the cavity, the substrate may be stuck on the bottom of the castable mold component. After the device body is released from the device mold, a physical condition such as temperature may apply to the device body. The castable mold component inside the device body will be melted from a solid phase to a liquid or a gaseous phase, so that it can be removed from the device body. Therefore the cavity is built inside the device body and the substrate is embedded.  
         [0025]     An embodiment for the device assembly, functional components, such as pillars, a slide substrate, and plugs will be put into the device body. The pillar and the substrate will supply a solid surface for chemicals or molecules coupling. The plugs will close part of the channels that left open when the elongated mold components were remove from the device body. Thus, the functional device is built with fully automatic flow control, probe configuration, and dynamic chemical or biochemical reaction.  
         [0026]     An advantage of the present invention of the fluidic programmable array device is that fully automatic system will avoid any intervention and contamination while performing the assay. Many factors need to be considered for microarraying work in a laboratory, such as temperature, humidity, and particles in air. With the microvalve and the micropump integration, once probe solutions and sample solutions are applied to the device, all procedures, such as coating, binding, coupling, washing, and reaction, are performed inside the spot reservoirs along the fluidic channels at a certain temperature under computer control. Failures from human intervention are decreased to minimum. Environmental contaminations are completely eliminated.  
         [0027]     A further advantage of above embodiments of the present invention is flexibility and customization of the array device. With the sophisticated fluidic channels, connecters, and spot reservoirs, the probe immobilization and configuration to the spot reservoirs can be performed easily. For example, cystic fibrosis is one of the most common autosomal-recessive disorders effecting one in 2500 births in the Caucasian population. Although there have been over 1000 mutations identified that cause cystic fibrosis, only 25 have been generally recommended for carrier screening. But for different racial groups the recommended mutations may somewhat be different. With the fluidic programming array device presented in this invention, the mutations detected for different racial groups can be easily configured in the array device.  
         [0028]     Another advantage of the above embodiments of the present invention is parallel detection of different samples and controls simultaneously with same or different mutations in same conditions. For example, in gene screening analysis, it is common that mutant-type, wild-type, and negative control samples are detected. With the fluidic programming array device, same kind of probes can be immobilized in the spot reservoirs along the probe fluidic channel; and different samples and controls can be loaded into the different sample channels, and reacted with the probes along the sample channel. The reaction and detection of the different samples and controls can be performed simultaneously at the same condition.  
         [0029]     A further advantage of the above embodiments of the present invention is dynamic reaction in channel. Currently, microarray chip have been widely used for DNA analysis and disease diagnosis. Various cDNA or oligonucleotides probes are synthesized or spotted on a solid substrate. Only the complementary probes react with specific DNA sample fragments coordinated with the probes. But the size of the probe spots is about 0.2 mm in diameter and the DNA sample is dropped onto the substrate to cover the all probe area. The concentration of the target DNA fragments is required to be high enough to make the hybridization reaction between the specific DNA fragment and the complementary probe occurred in the area of 0.2 mm in diameter, otherwise the specific DNA fragment may fail to match the complementary probe. This requirement makes that the efficiency of sample usage is very low and the reproducibility of the analysis and diagnosis is poor in current microarray technology. In embodiments of the present fluidic programmable array devices, the spot reservoirs are integrated along the fluidic channel. During hybridization reaction the target DNA sample is propelled along the fluidic channel forward and backward at a certain flow rate by a micropump. Because of sample solution movement, the each specific DNA fragment will find the complementary DNA probes at the spot reservoirs along the channel. With such dynamic reaction, the requirement for large amount and high concentration of sample is eliminated, the detection sensitivity and accuracy is increased. Therefore, the reproducibility and the efficiency will be highly increased.  
         [0030]     Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
     
    
     DESCRIPTION OF DRAWINGS  
       [0031]      FIG. 1  is a perspective view of a fluidic programmable array device having spot reservoirs, probe fluidic channels, and sample fluidic channels, in accordance with one embodiment of this invention.  
         [0032]      FIG. 2  is a top view of the array device shown in  FIG. 1 .  
         [0033]      FIG. 3  is a sectional view of the array device along a plan  3  in  FIG. 2 .  
         [0034]      FIG. 4  is a detail sectional view of one of spot reservoirs with two pinch microvalves on its both sides in the  FIG. 3 .  
         [0035]      FIG. 5  is a detail cross sectional view of one of the pinch microvalves in the  FIG. 4  with a piezoelectric actuator instead in accordance with one embodiment of this invention.  
         [0036]      FIG. 6  is a detail cross sectional view of one of the pinch microvalves in the  FIG. 4  with a thermopneumatic actuator instead in accordance with one embodiment of this invention.  
         [0037]      FIG. 7  is a perspective view of a fluidic programmable array device having spot reservoirs, fluidic channels, and fluidic connecters in accordance with one embodiment of this invention.  
         [0038]      FIG. 8  is a top view of the array device shown in  FIG. 7 .  
         [0039]      FIG. 9  is a sectional view of the array device along a plan  9  in  FIG. 8 .  
         [0040]      FIG. 10  is a detail sectional view of one of spot reservoirs in the  FIG. 9 , where the array device is on a programming stage with a capillary adapter.  
         [0041]      FIG. 11  is a detail sectional view of one of spot reservoirs in the  FIG. 9 , where the array device is on a programmning stage with a small well underneath.  
         [0042]      FIG. 12  is a sectional view of one of spot reservoirs in the  FIG. 9 , where the array device is on a reaction stage.  
         [0043]      FIG. 13  is a cross sectional view of one of the spot reservoirs with a solid substrate embedded in the spot reservoir and a fluidic connecter integrated with device body in accordance with one embodiment of this invention.  
         [0044]      FIG. 14  shows a perspective view of a device mold used for fabricating the fluidic programmable array device shown in  FIG. 7 .  
         [0045]      FIG. 15  is a top view of the device mold shown in the  FIG. 14 .  
         [0046]      FIG. 16  is a cross sectional view of the device mold shown in the  FIG. 14 . 
     
    
     DETAILED DESCRIPTION  
     DEFINITIONS  
       [0047]     The term “spot reservoir” as used herein refers to a small liquid cavity. The spot reservoir may be connected with a fluidic channel. Dimensions of the spot reservoirs are from millimeters to micrometers.  
         [0048]     The term “array device” as used herein refers to a device having an array structure composed of the spot reservoirs.  
         [0049]     The term “fluidic programmable array device” as used herein refers to an array device in which spot reservoirs can be configured with different probes through fluidic channels.  
         [0050]     The term “linear actuator” as used herein refers to a component that transforms electrical, magnetic, or thermal energy into a controllable linear motion. A linear actuator used in this present invention may be an electric-mechanical linear motion actuator, a piezoelectric component, a magnetostrictive component, a shape memory alloy, or a thermopneumatic motion actuator.  
         [0051]     The term “pinch microvalve” as used herein refers to a structure composed of a channel a recess, and a linear actuator. The linear actuator is placed through the recess or integrated close to the channel. A gap between the recess and the channel forms a deformable membrane when the device body is fabricated from elastomeric material. The linear actuator is capable of moving forward or backward, or upward and downward. When the linear actuator is activated, it exhibits a displacement to the deformable membrane that pinches the channel and closes the channel. When the activation is removed from the linear actuator, the deformable membrane will restore to its initial form for elastomeric property of the device body. Then the channel is re-opened.  
         [0052]     The term “elastomeric material” as used herein refers to a material that can cure by mixing a liquid base and a curing agent at a certain ratio. After solidification, the elastomeric material forms a structure having features that accurately reproduces features of the device mold and mold components. Other properties of the elastomeric material are good thermal stability, ability to repel water and form watertight seals, and flexibility. All these properties make the elastomeric material an important engine for fluidic and microfabrication applications. Examples of elastomeric materials are polydimethylsiloxane (PDMS), liquid silicone rubber, room temperature vulcanizing (RTV) rubber, polymeric rubber, or elastoplastic.  
         [0053]     The term “castable mold component” refers to a mold component made from one or more reversible, soluble, or sublimable materials. Reversible material refers to a material that is in solid phase at a certain temperature, but changes to liquid phase upon changes in the environment condition(s). Examples of the reversible materials are gel, fusible alloy, and eutectic alloy. Soluble material refers to a lipid material that is in solid at room temperature, but is soluble when upon contact with a solvent. Examples of soluble materials are soap, wax, sterols, and triglycerides. Sublimable material refers to a material that is in solid phase at a certain temperature or pressure, but changes to vapor phase upon changes in the environment condition(s), such as when heated or when the environment pressure is reduced. An example of sublimable material is ammonium salt, such as ammonium chloride (NH 4 Cl). A castable mold component is molded to a certain shape that is a complementary of a structure to be fabricated inside a device. A castable mold component can be removed from the device body after the device is molded.  
         [0054]     The term “elongated mold component” refers to a mold component having an elongated shape, such as a wire, a rod, or a sheet. A sheet may have a high aspect ratio in which the width and length are larger than the thickness. An elongated mold component can be made from steel, plastic, or silicon. An elongated mold component can also be a castable mold component that is cast from a mold having an elongated inner cavity.  
         [0055]     This invention presents several array devices and inside structures, which may be used for chemical and molecular analysis. Methods for fabricating the array devices are also presented.  
         [0056]      FIG. 1  shows a perspective view of a fluidic programmable array device  100  with 4×4 spot reservoirs  108 .  FIG. 2  shows a top view of the array device  100 .  FIG. 3  shows a cross sectional views along a plan  3  in  FIG. 2 .  FIG. 4  shows a detail sectional view of one of spot reservoirs  108  in with two pinch microvalves  130  and  131  along a fluidic channel  105  in the  FIG. 3 .  
         [0057]     The fluidic programmable array device  100  consists of a body  101  and a substrate  102 . Inside the body  101 , there are four fluidic channels  105  with their loading wells  103  and  104  for four target samples, four fluidic channels  111  with their loading wells  120  and  121  for four probes, 4×4 spot reservoirs  108  with their domes  109 , recesses  114  and  115  for linear actuators  133  and  134  on both sides of the each spot reservoir  108  beneath the fluidic channel  105  consisting of two pinch microvalves  130  and  131 , recesses  125  and  126  for linear actuators on both sides of the spot reservoir  108  beneath the fluidic channel  111 , and two sets of recesses  116 ,  117 , and  118 , and  122 ,  123 , and  124  with linear actuators beneath the fluidic channels  105  and  111  consisting of three-stage peristaltic pumps  127  and  128 . The spot reservoir  108  comprises a recess  110  and a portion of the substrate  112  at the recess  110 . The area  112  at the spot reservoir  108  on the substrate  102  is served as the base of the spot reservoir  108  for chemical or biological probes to be coupled on it. Other area on the substrate  102  is sealed or bonded with the bottom of the body  101 . The substrate  102  may be made of a material, such as silicon, glass, polypropylene, polycarbonate, and metal that is able to couple chemicals or molecules on it. The surface of the substrate  102  may be coated a material such as ploy-L-lysine, aminosilane, and aldehyde, that is able to couple chemicals or molecules on it. The body  101  of the array device  100  is made from elastomeric material, such as polydimethylsiloxane (PDMS), polymeric rubber, silicone rubber, or polymeric plastic. On the bottom of the array area of the body  101  there is a recess  119  for the substrate  102 . The device  100  is composed of 4 spot reservoirs  108  in a row along the fluidic channel  105  and 4 in a column along the fluidic channel  111  (4×4 array), but the number of the spot reservoirs  108  can be increased. The diameter of the spots reservoirs  108  can be from millimeters to micrometers. The height of the dome  109  may be from millimeters to micrometers. For example, if the spot reservoirs  108  with the pinch microvalves take 3 mm×3 mm space on the 25.4 mm×25.4 mm (1 inch×1 inch) substrate, an 8×8 spot array can be created in the center of the slide substrate. With microfabrication, it can be very easy to realize a spot reservoir with the microvalves in less than 1 mm×1 mm area. On a 25.4 mm×76.4 mm (1×3 inches) microscope slide, a 24×75 spot array device can be created in the center of the slide substrate. With microfabrication technology and a larger slide, more spot reservoirs can be created on the substrate slide. The spot array can be 50×100 to 100×1000. The dome  109  is a preferred shape for the spot reservoir  108 ; other shapes of the spot reservoirs  108  can be built. The each spot reservoir  108  can be same size or different sizes.  
         [0058]     Pinch microvalve in the array device  100 :  
         [0059]     As shown in  FIG. 4 , a deformable membrane  155  between the recess  114  and the channel  105  is formed when the device is fabricated from elastomeric material. On the substrate  102  there is a through hole  106 . The recess  114  in the body  101  and the through hole  106  on the substrate  102  are aligned. A linear actuator  133  is passed through. The shape of the tip of the linear actuator  133  is same as the cylindrical top of the cavity  114 . The tip of the linear actuator  133  is touched the top of the recess  114  when the linear actuator  133  is not activated. The linear actuator  133  is capable of moving forward or backward, or upward and downward along the recess  114  and the through hole  106  by an electromechanical motion component connected at the end of the linear actuator  133 . When the linear actuator  133  is activated and moves forward or upward, it will deform the deformable membrane  155  and pinch the channel  105  at the position of the recess  114 . When the linear actuator  133  is released and moves backward or downward, the membrane  155  returns to its initial form, and the channel  105  is re-opened. Therefore the linear actuator  133 , the deformable membrane  155 , the recess  114 , the through hole  106 , and the channel  105  form a integrated pinch microvalve  130  to control flow in the channel  105  in the device body  101 .  
         [0060]     On the other side of the spot reservoir  108  along the channel  105 , there are a recess  115  and the deformable membrane  156  in the body  101 , and a through hole  107  in the substrate  102 , which form another pinch microvalve  131  with a linear actuator  134 . Along the channel  111 , on both side of the spot reservoir  108 , there are recesses  125  and  126  that form pinch microvalves with through holes in the substrate  102  and other two linear actuators. So the spot reservoirs  108  in the device  100  can be separated from each other by these pinch microvalves.  
         [0061]     Three-stage peristaltic pump on the array device  100 :  
         [0062]     At one end of the channel  105  before the loading well  104 , three recesses  116 ,  117 , and  118  in series associated with linear actuators form three pinch microvalves along the channel  105 , as shown in  FIG. 3 . When the linear actuators move forward and backward in a sequence, such as  001 ,  011 ,  110 ,  100 , and  101  where 1 and 0 represent activated and nonactivated states of the linear actuator, the channel  105  will be closed or open in the sequence at the positions of the recesses  116 ,  117 , and  118  respectively. This sequential movement squeezes fluid moving forward in the channel  105 . The three pinch microvalves compose of a three-stage peristaltic pump  127  that propels the fluid in the channel  105  forward from the loading well  104  to the loading well  103 . With a reverse sequence of the movements of the linear actuators, the fluid in the channel  105  is propelled backward from the loading well  103  to the loading well  104 . At one end of the channel  111  before the loading well  121 , three recesses  122 ,  123 , and  124  associated with linear actuators form another three-stage peristaltic pump  128  that propels the fluid in the channel  111  forward from the loading well  121  to the loading well  120  or backward from the loading well  120  to the loading well  121 .  
         [0063]     Preparation of the substrate surface:  
         [0064]     For probe immobilization on the substrate  112  at the spot reservoir  108 , as an example of DNA analysis application, the surface of the substrate  102  or the whole solid substrate  102  can be coated with either poly-L-lysine or aminosilane to give an amino group surface or covalent attachment to link the probe by sharing electrons between adjacent atoms. The substrate  102  can be treated with a procedure for slide surface coating in conventional microspot technology. After it is treated, the substrate is wedged into the bottom of the device.  
         [0065]     The surface  112  at the spot reservoir  108  can be also treated on chip. The untreated substrate  102  is wedged onto the bottom of the device body  101 . The substrate  102  and the recesses  110  form the spot reservoir  108 . Coating solutions can be loaded into the loading well  104 , and propelled along the channel  105  into the spot reservoir  108 . Following the protocal for slide surface coating in conventional microspot technology, the surface  112  can be coated.  
         [0066]     Probe programming on the array device  100 :  
         [0067]     To configure the four spot reservoirs  108  along the each channel  105  with different probes, first, the pinch microvalves at the position of the recesses  106  and  107  are activated to close the channel  105  at both sides of the spot reservoir  108 . Second, probe solutions are loaded into the each loading inlet well  121 . In this embodiment there are four channels  111  with four loading inlet wells  121  and four loading outlet wells  120 . Four different probes can be loaded into the four loading inlet wells  121  to configure the four spot reservoirs  108  along the each channel  111  respectively. Third, the three-stage peristaltic pump  128  propels the probe solution through the channel  111  from the loading inlet well  121  to the loading outlet well  120 . When the probe solutions flow into the spot reservoirs  108  along the channels  111 , the surface of the substrate  112  at the spot reservoirs  108  will absorb or couple the molecules or chemicals of the probes by ionic interaction or covalent attachment. Therefore the spot reservoirs  108  along the channel  111  are configured with one of the four molecular or chemical probes. During the probe configuration the probe solution can be pumped forward and backward along the channel  111  by the three-stage peristaltic pump  128  at a controllable flow rate. This dynamic flow of the probe solution will increase efficiency of the reaction between the surface  112  at the spot reservoir  108  and the probe solution, and the usage efficiency of the probe solution. After the reaction between the surface  112  at the spot reservoir  108  and the probe solution, the probe solution is propelled into the either loading well  121  or  120  and collected. A wash bath solution can be loaded into the loading well  121  and pumped through the channels  111  and the spot reservoirs  108  to wash the residual probe solutions into the loading outlet well  120 . Then the solutions in the loading well  120  can be removed from the device  100 .  
         [0068]     Hybridization reaction in the array device  100 :  
         [0069]     After the probe configuration in the spot reservoirs  108 , the microvalves at the position of the recesses  106  and  107  are deactivated to open the channel  105  at both sides of the spot reservoir  108 . At the same time, the microvalves at the position of the recesses  125  and  126  are activated to close the channel  111  at both sides of the spot reservoir  108 . Then, the sample solutions are loaded into the loading inlet well  104 . In this embodiment there are the four sample channels  105  with the four loading inlet wells  104  and the four loading outlet wells  103 . Four different samples can be loaded into the four loading inlet wells  104 . The three-stage peristaltic pump  127  propels the sample solutions through the channels  105  from the loading inlet wells  104  to the loading outlet wells  103 . In this embodiment, DNA samples are used to be an example of the applications of the array device  100 . When the DNA sample solutions flow into the spot reservoirs  108  along the channels  105 , hybridization reaction will be happened in the spot reservoirs  108  between the probes coupled on the surface  112  and the sample solutions. During the hybridization reaction, the sample solutions can be pumped forward and backward along the channel  105  at a certain flow velocity by the three-stage peristaltic pump  127 . This dynamic flow of the sample solution will increase efficiency of the reaction between the probes on the surface  112  at the spot reservoir  108  and the sample solution. The efficiency of the sample solution usage will be increased also. After the reaction, a wash bath solution can be loaded into the loading inlet wells  104  and pumped through the channels  105  and the spot reservoirs  108  to wash the unbound sample solutions into the loading outlet wells  103 . Then the solutions in the wells  103  can be removed from the device  100 .  
         [0070]     Hybridization reaction is a preferred example for DNA analysis application, other chemical or biochemical reaction can be also applied in this present array device for chemicals, molecules, cells, or tissues detection and analysis. For example, for protein analysis, antibody probes can be configured in the spot reservoirs, and antigen samples can be loaded into the device. Then antibody-antigen interactions will be occurred in the spot reservoirs.  
         [0071]     For the body  101  is optical transparent, the result can be read from the top of the array device  100 . The array device  100  can be put on a translation stage with laser induced fluorescence detection. When the translation stage moves, the array device  100  is scanned and the reaction result in the each spot reservoir  108  is read. The body  101  is not necessary to be optical transparent. The substrate  102  can be removed from the device body after the reaction, and put on a commercial-available reader for microarray or microspot to detect the reaction result at the positions of the spot reservoirs  108 . The methods for the detection can be confocal laser scanning and sensitive CCD picturing.  
         [0072]      FIGS. 5 and 6  illustrate other two embodiments of integrated pinch microvalves.  FIG. 5  shows a pinch microvalve activated by a linear solid microactuator  150 .  FIG. 6  shows a pinch microvalve activated by a thermopeumatical microactuator  160 .  
         [0073]     In  FIG. 5 , as another embodiment of the microvalve by the linear solid microactuator  150 ,  5  piezoelectric components  151  and a cylindrical pinch head  152  are stacked together to compose the microactuator  150  in the recess  114  on the substrate  102 . Piezoelectric movement arises from the dimensional changes generated in certain crystal materials when they are subjected to an electric field. Typical piezoelectric materials are quartz, lead zirconate titanate, lithium niobate, and some polymers, such as polyvinyledene fluoride. The response of piezoelectric materials to changes of the electric field is very quickly and repeatable. When a voltage is applied to the 5 piezoelectric components  151 , they generate a linear movement that pushes the cylindrical pinch head  152  upward. The cylindrical pinch head  152  will deform the membrane  155  between the recess  114  and the channel  105 . The deformation closes the channel  105 . When the voltage is released from the piezoelectric components  151 , the membrane  155  will restore to its initial shape by elastomeric property of the device body  101 . The channel  105  is re-opened.  
         [0074]     Other components instead of piezoelectric components  151  can be also used as the linear solid microactuator  150 . Examples of such components are shape memory alloy, electroactive polymer (EAP), and magnetostrictive component.  
         [0075]     In  FIG. 6  shows another embodiment of the microvalve by the thermopeumatical microactuator  160 . The microactuator  160  is composed of a sealed cavity  163  and a microheater  162 . The cavity  163  is formed by the recess  114  and the substrate  102 , and filled with a low boiling point liquid, such as methyl chloride, or fluorinert. The microheater  162  is built inside the cavity  163 . When the microheater  163  is connected to a current, the temperature in the cavity  163  increases, the pressure inside grows because of the gas generating from the liquid-gas phase transitions, and the deformable membrane  155  is inflated. The deformation of the membrane  155  will close the channel  105 . The microheater  163  can be a small diode, a resistor, or other integrated semiconductors on the substrate  102 . When the current is disconnected to the microheater  163 , the temperature drops, and the pressure inside decreases, the membrane will restore to its initial form by elastomeric property of the material of the device body  101 . The channel  105  is re-opened.  
         [0076]     As another embodiment,  FIG. 7  shows a perspective view of a fluidic programmable array device  200  with 4×4 spot reservoirs that can be configured with different probes individually.  FIG. 8  is a top view of the array device shown in  FIG. 7 .  FIG. 9  shows a cross sectional views along a plan  9  in  FIG. 8 .  FIG. 10  shows a detail of one of spot reservoirs  209  in the sectional view in the  FIG. 9 , where the array device  200  is on a programming stage  230  with a capillary adapter  235 .  FIG. 11  shows a sectional view of one of spot reservoirs  209  in the  FIG. 9 , where the array device  200  is on a programming stage  240  with a probe programming well  243  underneath.  FIG. 12  shows a sectional view of one of spot reservoirs  209  in the  FIG. 9 , where the array device  200  is on a reaction stage  250 .  
         [0077]     The fluidic programmable array device  200  consists of a body  201  and pillars  208 . Inside the body  201 , there are four fluidic channels  205  with their loading wells  203  and  204  for four target sample solution, 4×4 spot reservoirs  209 , recesses  206  and  207  for linear actuators on both sides of the each spot reservoir  209  along the fluidic channels  205  consisting of pinch microvalves  221  and  222 , and a set of recesses  216 ,  217 , and  218  for linear actuators beneath the fluidic channel  205  consisting of a three-stage peristaltic pump  220 . The body  201  of the array device  200  is made from elastomeric material, such as polydimethylsiloxane (PDMS), polymeric rubber, or polymeric plastic. The pillar  208  is made from a solid material, such as silicon, glass, polypropylene, polycarbonate, or metal.  
         [0078]     On the bottom of the array area of the body  201  there is an array of recesses  210  for accepting the pillars  208 . Each pillar  208  corresponds to the each spot reservoir  209  in the body  201 . The diameter of the recess  210  equals to the diameter of the pillar  208 . When the array device  200  is assembled, the pillar  208  is wedged into the recess  210 . The contact surface between them forms a watertight sealing. The top dome of the recess  210  and the top surface  212  of the pillar  208  form the spot reservoir  209 . The top surface  212  of the pillar  208  will serve as the base of the each spot reservoir  209 . In this preferred example, the pillar  208  and the recess  210  are in cylindrical shape, but other shape can be also applied.  
         [0079]     The 4×4 spot array device  200  shown in  FIG. 5  is a preferred example, but the one spot reservoir  209  and the one channel  205  can compose the device  200 . Also the number of the spot reservoirs  209  in the device  200  can be increased. The diameter of the pillar  208  can be from millimeters to micrometers. The height of the spot reservoir  209  may be from millimeters to micrometers. For example, if the pillar  208  with the microvalve  221  takes 3 mm along the channel  205 , the channel-to-channel space is 4 mm, an 8×6 spot array can be created in a 25.4 mm×25.4 mm (1 inch×1 inch) center area of the device  200 . With microfabrication, it can be very easy to realize a pillar and a pinch microvalve in several hundreds micrometers in diameters. If the spot reservoir  209  and the microvalve  221  take a 1 mm along the channel  205  and the space between the channels  205  is 1 mm, in a 25.4 mm×76.4 mm (1×3 inches) center area of the device  200 , a 24×75 spot array device can be created. The number of the spot reservoirs  209  in the device  200  is 1800 spots. With microfabrication technology, more spot reservoirs can be created in the device  200 . The spot array can be 50×100 to 100×1000. The dome of the spot reservoir  209  is a preferred shape; other shapes for the spot reservoirs  209  can be built. The diameter of the pillar  208  can be from millimeters to micrometers. The each pillar  208  can be same size or different sizes.  
         [0080]     The four spot reservoirs  209  in the  FIG. 9  are connected by the channel  205 . The each spot reservoir  209  can be separated by the pinch microvalves  221  and  222  along the channel  205 . On each end of the channel  205  there are loading wells  203  and  204  for sample loading. Along the channel  205  there is a micropump  220  to propel the sample solution through the channel  205 .  
         [0081]     In the preferred embodiment of this invention, the channel  205  is used for sample solution and the channel  211  for probe solution. In practice, the channel  205  can also be assigned for probe solution and the channel  211  for sample.  
         [0082]     The surface coating on the surface  212  of the each pillar  208 :  
         [0083]     The top surface  212  of the pillar  208  serves as the base of the spot reservoir  209 . On the center of the each pillar  208 , there is a small channel  211 . The channel  211  is used to delivery the probe solution into the spot reservoir  209 . As an example of DNA analysis application, the surface should be coated with poly-L-lysine, aminosilane or other conventional microarray protocol to allow for efficient probe coupling. The surface treatment can be achieved on each pillar  208  before it is assembled to the device body  201 . The procedure can follow the method of the slide surface coating in conventional microspot protocol. Instead, the pillars  208  can be put in a tube soaked with coating solution.  
         [0084]     The surface treatment can be also achieved on each pillar  208  after it is assembled to the device body  201 . Coating solution can be loaded into the spot reservoir through the channel  211  or the channel  205 . The procedure then can follow the method for slide surface coating in conventional microspot protocol.  
         [0085]     Pinch valve on the array device  200 :  
         [0086]     As shown in  FIG. 10 , between the recess  206  and the channel  205  a deformable membrane  213  is formed when the device is fabricated from elastomeric material. On the socket stage  230  for probe programming there is a through hole  231 . The recess  206  in the body  201  and the through hole  231  are aligned. The tip shape of a linear actuator  233  is same as the cylindrical top  214  of the recess  206 . The linear actuator  233  is inserted into the recess  206 . The tip of the linear actuator  233  is touched the top  214  of the recess  206 . The linear actuator  233  is capable of moving forward or backward, or up and down along the recess  206  and the through hole  231  by a linear motion actuator connected at another end of the linear actuator  233 . When the linear actuator  233  moves forward or upward, it will pinch the channel  205  at the position of the recess  206 . The membrane  213  is deformed and the channel  205  is closed. When the pin actuator  233  is moved backward, the membrane  213  restores to its initial form, and the channel  205  is re-opened. Therefore the linear actuator  233 , the membrane  213 , the recess  206 , the through hole  231 , and the channel  205  compose of the pinch microvalve  221  to control flow in the channel  205 .  
         [0087]     On the other side of the spot reservoir  209  along the channel  205 , the pinch microvalve  222  is comprised along the channel  205 . Therefore, the spot reservoirs  209  can be separated from each other by these pinch microvalves  221  and  222  along the channels  205 .  
         [0088]     Integrated pinch microvalves, such as the pinch microvalves built in the device  100  with the piezoelectric components or a thermopneumatic actuator, can be also created in the device  200 .  
         [0089]     Probe programming on the array device  200 :  
         [0090]     The each spot reservoir  209  can be configured with different probes.  FIG. 10  shows the sectional view of one of the spot reservoir  209  of the array device  200  on the socket stage  230  for probe programming. A socket  237  on the stage  230  is used to accept the pillar  208  on the device  200 . The connection between the socket  237  and the pillar  208  is watertight. There is a center hole  236  on the bottom of the socket  237 . The diameter of the hole  236  is same as the diameter of the channel  211 . The hole  236  is aligned with the center hole  211  on the pillar  208 . On the bottom of the socket stage  230 , a capillary adapter  235  is built corresponding to the each socket  237 . The capillary adapter  235  is used to connect a capillary that deliver a probe solution into the device  200 . To configure the spot reservoir  209 , the probe solution will be propelled through the capillary, the hole  236 , and the channel  211 , into the reservoir  209 . Then the microvalves  221  and  222  at the position of the recesses  206  and  207  are activated to close the channel  205  at both sides of the spot reservoir  209  to prevent a cross contamination of the probe solution along the spot reservoirs  209  through the channel  205 .  
         [0091]     When the probe solutions are in the spot reservoirs  209 , the surface  212  of the pillar  208  will absorb or couple the molecules or chemicals of the probes by ionic interaction or covalent attachment. Therefore the each spot reservoir  209  is configured with the molecular or chemical probe. After the probe solution is coupled onto the surface  212 , the residual probe solution can be withdrawn through the channel  211  and the hole  236  from the spot reservoir  209 . The, pinch microvalves  221  and  222  at the position of the recesses  206  and  207  are deactivated to open the channels  205 . A wash bath solution can be loaded into the loading wells  204  and pumped through the channels  205  and the spot reservoirs  209  to wash the residual probe solutions into the wells  203 . Then the solutions in the wells  203  can be removed from the device  200 .  
         [0092]     Another embodiment of this invention for probe programming on the array device  200  is shown in  FIG. 11  by capillary action. Capillary action is the ability of a capillary to draw a liquid upwards against the force of gravity. It occurs when the lower end of the capillary is placed in a liquid such as water, surface tension pulls the liquid column up. The height h in metres of a liquid column is given by:  
       h   =       2   ⁢   T   ⁢           ⁢   cos   ⁢           ⁢   θ       ρ   ⁢           ⁢   g   ⁢           ⁢   r           
 
 where T=interfacial surface tension (N/m), θ=contact angle, ρ=density of liquid (kg/m 3 ), g=acceleration due to gravity (m/s 2 ). For a water-filled glass tube in air at sea level, T=0.0728 N/m at 20° C., θ=20°, ρ=1000 kg/m 3 , g=9.80665 m/s 2 , so the height of the liquid column is given by  
       h   ≈       1.4   ×     10     -   5         r         
 
         [0093]     In this embodiment, the diament of the channel  211  is 0.125 mm, the height of the liquid column will be 112 mm. In the  FIG. 11 , the pillar  208  is inserted into the probe solution in a small well  244  beneath a socket stage  240  for probe programming. The liquid level in the well  243  is at 244. The height of the pillar  208  is 10 mm. The capillary action is easy to pull the probe solution into the spot reservoir  209  from the liquid level  244  to the surface  212 . After the probe solution is in the spot reservoir  209 , the microvalves  221  and  222  at the position of the recesses  206  and  207  in the device body  201  and the through holes  241  and  242  on the stage  240  are activated to close the channel  205  at both sides of the spot reservoir  209  to prevent cross contamination of the probe solutions.  
         [0094]     Hybridization reaction in the array device  200 :  
         [0095]     After the probe programming in the spot reservoirs  209 , the device  200  can be removed from the programming stage  230  or  240 , and put on a reaction stage  250 , as shown in  FIG. 12  for one of the spot reservoir  209  of the device  200 . On the reaction stage  250 , there is an array of dead-end socket  251  corresponding to the array of the pillars  208  on the device  200 . The end  252  of the socket  251  will seal the end of the channel  211  of the pillar  208 . A heater may be attached to the reaction stage  250  to maintain a certain temperature applied to the device  200 . The sample solutions are loaded into the inlet wells  204 . In this embodiment there are the four channels  205  with the four inlet wells  204  and the four outlet wells  203 . Four different samples can be loaded into the four inlet wells  204 . The three-stage peristaltic micropump  220  propels the sample solutions through the channels  205  from the wells  204  to the wells  203 . In this embodiment, DNA samples are used to be an example of the applications of the array device  200 . When the DNA sample solution flows into the spot reservoirs  209  along the channels  205 , hybridization reaction will be happened in the spot reservoirs  209  between the probes coupled on the surface  212  and the sample solutions. During the hybridization reaction, the sample solutions can be pumped forward and backward along the channel  205  by the three-stage peristaltic micropump  220 . This dynamic flow of the sample solution will increase efficiency of the reaction between the probes on the surface  212  at the spot reservoir  209  and the sample solution. The usage efficiency of the sample solution will also be increased. After the reaction a wash bath solution can be loaded into the wells  204  and pumped through the channels  205  and the spot reservoirs  209  to wash the residual sample solutions into the wells  203 . Then the solutions in the wells  203  can be removed from the device  200 .  
         [0096]     For the body  201  is optical transparent, the result can be read from the top of the array device  200 . The array device  200  can be put on a translation stage with laser induced fluorescence detection. When the translation stage moves, the array device  200  is scanned and the reaction result in the each spot reservoir  209  is read. The methods for the detection can be laser induced fluorescence detection, UV absorption detection, or other measurements.  
         [0097]      FIG. 13  shows a spot reservoir  309  in an array device  300 . The device  300  is similar to the device  200  except that the spot reservoir  309  is embedded in a device body  301 , the pillar  208  is replaced by an embedded substrate  302  in the spot reservoir  309 , and the channel  211  in the pillar  208  is integrated as a channel  311  with a fluidic connector  308  inside the device body  301 . The device body  301  of the device  300  is made from elastomeric material, such as polydimethylsiloxane (PDMS), polymeric rubber, or polymeric plastic. The substrate  302  is made from a solid material, such as silicon, glass, polypropylene, polycarbonate, or metal.  
         [0098]     In the device  300 , recesses  306  and  307  and a channel  305  associated with linear actuators compose of pinch microvalves same as the microvalves  221  and  222  in the device  200 . The channel  305  connects the spot reservoirs  309 . Numbers of the channel  205  and the spot reservoirs  309  can be designed in the device  300  according to application requirements.  
         [0099]     On the substrate  302 , there is a small hole  303  connected with the channel  311 . The channel  311  is used to delivery the probe solution into the spot reservoir  309 . For probe immobilization on the surface  304  in the spot reservoirs  309 , the surface  304  could be either amine- or lysine-coated to absorb the probe by ionic interaction or covalent attachment to link the probe by sharing electrons between adjacent atoms.  
         [0100]     Other procedures and operations of the device  300  are similar to those of the device  200 .  
         [0101]     Methods for device fabrication:  
         [0102]     Referring to  FIG. 14  to  16 , methods with a device mold  500  is used to fabricate the array device  200 . The methods with slight modifications on molds can be also used for the fabrication of the device  100  and  300 . The device mold  500  is formed by assembling mold body  501  with mold components  502  to  508 . The mold body  501  consists of sidewalls  520  and a base  515 . The mold component  502  defines the recess  210  in the device body  201 . The mold component  503  and  504  define the loading wells  203  and  204  in the device body  201 . The elongated mold component  505  defines the channel  205  in the device body  201 . The mold components  506  and  507  define the recesses  206  and  207  in the device body  201 . On the sidewalls  520 , there are slots  510  and  511  to accept the elongated mold component  505  to predefine the position of the channel  205  in the device  200 . On the mold component  503  and  504  there is a slot  513  and  514 . The elongated mold component  505  is passed through the slots  513  and  514  to position the mold components  503  and  504  in the device mold  500 . On the dome of the mold component  502  there is also a slot  512 . It is used to support the elongated mold component  505  at the predefined position and to create the connection of the channel  205  and the spot reservoir  209  in the device  200 . The mold components  508  is used to create the recesses  216 ,  217 , and  218  for the micropump  220  in the device  200 . On the base  515  of the mold body  501 , there are predefined holes  519  and  516 - 518  to accept the mold components  502  and  506 - 508 . There is an open space  509  in the mold  500  for pouring liquid elastomeric material into it to cast the device  200  from the mold  500 .  
         [0103]     To create the deformable membranes  155  in the device  100  and  213  in the device  200 , the set of mold components may include the mold component  506  and the elongated mold component  505 . The two mold components may be placed in the device mold  500  with a gap between the tip of the mold component  506  and the elongated mold component  505 . The gap can be designed from tens micrometers to hundreds micrometers according to the type of the linear motion actuators. For the piezoelectric motion component  150  and the thermopneumatic motion component  160 , the displacement is relatively smaller. The gap should be in tens millimeters range, for example 30-90 micrometers. For the electric-mechanical motion actuator, the displacement is larger, the gap can be in hundreds micrometers range, for example 100-500 micrometers. For the slots  510  and  511  on the sidewall  520  and the slots  512  on the domes of the mold components  502 , the elongated mold component  505  can be sustained straight and positioned. The gap can be kept consistent at the each position of the mold components  506  along the elongated mold component  505 . After the device  100  or  200  is cast, the mold components are removed from the device mold and the device body, the recess  106  or  206  and the channel  105  or  205  are formed. So the deformable membrane is created.  
         [0104]     To create the spot reservoir  109  with the two perpendicular channels in the device  100 , a mold component with two perpendicular slots can be used. The two slots cross at a different level, one is positioned higher than another. When the device mold is assembled, two elongated mold components will be passed through the two holes to created perpendicular channels  105  and  111  at the spot reservoir  109 .  
         [0105]     To create the embedded spot reservoir  309  in the device  300 , the set of mold components may include a castable and an elongated mold component. The castable mold component has a complementary shape suitable for forming the spot reservoir  309 . The elongated mold component has a complementary shape suitable for forming the channel  305  connecting the spot reservoirs  309  in the device  300 . On the castable mold component there is a slot with a same dimension and shape as the elongated mold component. The castable mold component may be made of a reversible, soluble, or sublimable material, such as fusible alloy, soap, wax, or ammonium salt.  
         [0106]     To embed the substrate  302  inside the spot reservoir  309 , the substrate  302  may be stuck on the bottom of the castable mold component. A post supporting the substrate  302  and the castable mold component is placed on the base of the device mold. The mold body may have a sidewall with a hole at a predefined position relative to the mold body. Assembling the device mold may include inserting the elongated mold component through the slot on the sidewall of the device mold, the slot on the castable mold component, and the slot on the opposite sidewall of the device mold. The elongated mold component aligns the castable mold component in the device mold. After the device body is released from the device mold and the elongated mold component and the post are pull out from the device mold, the channels  305  and  311  are created. A physical condition such as temperature may apply to the device body. The castable mold component inside the device body will be melted from a solid phase to a liquid or a gaseous phase, so that it can be removed through the channel  305  or  311  from the device body  301 . Therefore the spot reservoir  309  is built inside the device body  301  and the substrate  302  is embedded.  
         [0107]     Fabrication may include the following steps:  
         [0108]     Step  1 : Fabricating mold component and mold body  
         [0109]     To create a recess such as the recess  206  in the device  200 , the mold component  506  with a cylindrical tip can be machined from a wire. The mold component  502  with a dome tip can also be machined from a wire for creating the recess  210  in the device  200 . The laser drilling can be used to create the slot  512  on the dome. The mold component  503  with the slot  513  can be also made from a wire and laser drilling. The elongated mold component can be made from a wire. The sidewall  520  and the base  515  can be made from conventional machining. The device mold can be open on the top for casting, like  500 , or be a closed structure for injection casting.  
         [0110]     If a castable mold component is used to create a embedded chamber such as the spot reservoir  309  in the device  300 , the castable mold component may be fabricated from reversible, soluble, or sublimable material by a component mold. The reversible, sublimable, or soluble material is poured, injected, or compressed into the component mold. After the material solidifies, the castable mold component is separated from the component mold.  
         [0111]     Step  2 : Assembling the device mold  
         [0112]     The device mold  500  is assembled by procedures below: placing the sidewall  520  on the base  515 ; inserting the mold components  502  and  506 - 508  into the holes  519  and  516 - 518  on the base  515 ; and passing the elongated mold component  505  through the slot  510  on the sidewall  520 , the slot  513  on the mold component  503 , the slots on the dome of the mold component  502 , the slot  514  on the mold component  504 , and the slot  511  on the sidewall  520 .  
         [0113]     Step  3 : Coating the surfaces of the device mold  
         [0114]     A mold release agent may be sprayed on the surface of the mold body  501  and the mold components assembled in it. This step is used to prevent adherence of the elastomeric material on the mold body  501  and the mold components when the mold body  501  and the mold components are removed from the device body  201 . This step may be omitted if the adherence is not an issue.  
         [0115]     Step  4 : Casting the device body  
         [0116]     Liquid elastomeric material is poured or injected into the device mold  500  to fill in the space defined by the mold body  501  and the mold components. The liquid elastomeric material is selected so that its curing temperature is lower than the melting (or sublimation) temperature of the castable mold components if the castable mold components are used.  
         [0117]     Step  5 : Removing the mold components from the device mold  
         [0118]     First, the elongated mold component  505  is pull out from the device mold  500  through the slot  510  or  511 . Then the mold components  503  and  504  can be removed from the top of the device mold  500 . The mold components  502 , and  506 - 508  can be pull out from the bottom of the device mold  500 .  
         [0119]     If the castable mold component is used, the device mold  500  with the device body  201  may be heated so that the castable mold component is melted (or vaporized), or a solvent may be used to inject to the soluble mold component to dissolve the mold components. The melted or dissolved mold component can be removed by use of vacuum suction or centrifuge.  
         [0120]     Step  6 : Releasing the device body from the mold body  
         [0121]     The sidewall  520  can be removed from the base  515 . The device body  201  can be then released from the mold base  515 .  
         [0122]     Step  7 : Assembling the device  200  with functional components  
         [0123]     The channel built by the elongated mold component  505  has an opening from the loading wells to the side of the device  200  after the device is released from the mold. Plugs will be inserted into the channels  205  to close this part of the channel. As an alternative method, liquid glue may be injected to this part of the channel instead.  
         [0124]     Functional components, such as the glass substrate  102  and the pillars  208  will be assembled into the device body  101  or  201  at the predefined position. If the sealing between the device body and the functional components exhibits watertight, the device will be ready to use. Otherwise some glue may be applied to seal the functional components in the device body.  
         [0125]     The techniques described herein the fluidic programmable array devices for microarray and microspot technology can be used in many different applications, including analytical chemistry, biological diagnosis, medical diagnosis, food testing, environment testing, biodefence, and drug detection and screening. Although some examples have been discussed above, other implementation and applications are also within the scope of the following claims.