Patent Publication Number: US-2002012916-A1

Title: A method of reducing contamination in an essay vessel

Description:
REFERENCE TO RELATED APPLICATIONS  
     [0001] This case is a continuation-in-part application of U.S. patent application Ser. No. 415,796, filed on Oct. 11, 1999, which is a conversion of provisional patent application Ser. No. 60/104,191, filed on Oct. 14, 1998. 
    
    
     
       BACKGROUND  
       [0002] The following relates generally to a structure and a method for determining an item of interest in a sample. More specifically, the following relates to determining an item of interest that may be or include all or portions of a specific region of DNA, RNA, fragments, complements, peptides, polypeptides, enzymes, prions, proteins, messenger RNA, transfer RNA, mitochondrial RNA or DNA, antibodies, antigens, allergens, parts of biological entities such as cells, virons or the like, surface proteins, functional equivalents of the above, etc.  
       [0003] To provide information about a patient&#39;s health, a number of tests can be performed on a patient sample, such as the patient&#39;s bodily fluids. These bodily fluids may include serum, whole blood, urine, swabs, plasma, cerebra-spinal fluid, lymph fluids, tissue solids, etc. The tests performed on the patient&#39;s bodily fluids can determine an item of interest, such as those stated above, in the bodily fluids. Based on the determination of the item of interest in the patient&#39;s bodily fluids, information about the patient&#39;s health status can be obtained.  
       SUMMARY  
       [0004] Embodiments described herein provide methods of processing a sample containing at least one biological element. One method comprises introducing a first conductor and a second conductor into the sample. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted to reduce an ability of the at least one biological element to be amplified or detected in a PCR reaction process.  
       [0005] In another method, at least one biological element in a sample is removably attached to a binding member. A first conductor and a second conductor are introduced into the sample. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted such that the at least one biological element is removed from the binding member.  
       [0006] In an additional method, a first conductor and a second conductor are introduced into the sample containing at least one biological element. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted to unzip the at least one biological element.  
       [0007] In a further method, a first conductor and a second conductor are located adjacent a sample containing at least one biological element. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted to reduce an ability of the at least one biological element to be amplified or detected in a PCR reaction process.  
       [0008] In an additional method, at least one biological element in a sample is removably attached to a binding member. A first conductor and a second conductor are located adjacent the sample. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted such that the at least one biological element is removed from the binding member.  
       [0009] In yet a further method, a first conductor and a second conductor are located adjacent a sample containing at least one biological element. A voltage is applied between the first conductor and the second conductor. The voltage is adjusted to unzip the at least one biological element. 
     
    
    
     BRIEF DESCRIPTION OF DRAWINGS  
     [0010]FIG. 1 is a perspective view of a structure described herein;  
     [0011]FIG. 2 is a perspective view of the structure of FIG. 1;  
     [0012]FIG. 3A is a generic top view of another structure described herein;  
     [0013]FIG. 3B is a perspective view of the structure shown in FIG. 3A;  
     [0014]FIG. 4 is a perspective view of a sample queue for use with the structure of FIGS. 3A and 3B;  
     [0015]FIGS. 5A through 5F are perspective views of elements for use with the structure shown in FIGS. 3A and 3B;  
     [0016]FIG. 6 is a perspective view of a container and a carrier for use with the structure of FIGS. 3A and 3B;  
     [0017]FIG. 7 is a perspective view of a pipette tip loader for use with the structure shown in FIGS. 3A and 3B;  
     [0018]FIG. 8 is a perspective view of another embodiment of a pipette tip loader for use with the structure shown in FIGS. 3A and 3B;  
     [0019]FIG. 9 is a perspective view of a container loader for use with the structure of FIGS. 3A and 3B;  
     [0020]FIG. 10 is a perspective view of a container transporter for use with structure shown in FIGS. 3A and 3B;  
     [0021]FIG. 11 is a magnified view of a portion of FIG. 10;  
     [0022]FIGS. 12A through 12P are perspective views of various embodiments of the container shown in FIG. 1;  
     [0023]FIG. 13 illustrates engagement of the container of FIG. 12E with a mixer;  
     [0024]FIG. 14 shows a port provided in operative relationship with the process path of FIGS. 3A and 3B;  
     [0025]FIG. 15 is an exploded perspective view of a pipettor for use with the structure of FIGS. 3A and 3B;  
     [0026]FIG. 16 illustrates one operation of the pipettor of FIG. 15;  
     [0027]FIG. 17 illustrates another operation of the pipettor of FIG. 15;  
     [0028]FIG. 18 is an isometric view of a structure substantially similar to the structure of FIGS. 3A and 3B;  
     [0029]FIG. 19 is an isometric view of a structure substantially similar to the structure of FIG. 18;  
     [0030]FIG. 20 is a top view of another structure substantially similar to the structure of FIGS. 3A and 3B;  
     [0031]FIG. 21 is a top view of an additional structure substantially similar to the structure of FIG. 20;  
     [0032]FIG. 22 is a top view of a further structure substantially similar to the structure of FIG. 21;  
     [0033]FIG. 23 is a top view of another structure substantially similar to the structure of FIG. 22;  
     [0034]FIG. 24 is a top view of yet a further structure substantially similar to the structure of FIG. 23;  
     [0035]FIG. 25 is a top view of yet a further structure similar to the structure of FIGS. 3A and 3B;  
     [0036]FIG. 26 is a top view of yet a further structure similar to the structure of FIGS. 3A and 3B;  
     [0037]FIGS. 27A through 27F are perspective views of a container and seal for use with the structure of FIGS. 3A and 3B;  
     [0038]FIG. 28 is a perspective view of an optical configuration for use with the structures described herein;  
     [0039]FIG. 29 is a generic view of operation of a portion of the structures described herein;  
     [0040]FIG. 30A is a sectional view of a portion of the structures described herein;  
     [0041]FIG. 30B is a top view of the portion of FIG. 30A;  
     [0042]FIG. 31 is a sectional view of a portion of the structures described herein;  
     [0043]FIG. 32A is a sectional view of a portion of the structures described herein;  
     [0044]FIG. 32B is a top view of the portion of FIG. 32A;  
     [0045]FIG. 33 is a generic plan view of a portion of the structures described herein; and  
     [0046]FIG. 34 is a schematic diagram of a circuit described herein. 
    
    
     DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS  
     [0047] The embodiments described herein relate to methods and structures for determining an item of interest in a sample. The item of interest may be a specific region or regions of DNA or RNA, or may be fragments, complements, peptides, polypeptides, enzymes, prions, proteins, messenger RNA, transfer RNA, mitochondrial RNA or DNA, antibodies, antigens, allergens, parts of biological entities such as cells, virons or the like, surface proteins, functional equivalents of any of these, concentrations of any of these or any other desired element of the sample. In an exemplary embodiment, the item of interest may be selected from, but is not limited to specific DNA or RNA regions, antibodies, or antigens including but not limited to, CT, CT/GC, MT, HCV, HBV, HPV, HIV, CMV, HLA, HTLV, and other items related, but not limited to, infectious diseases, genetic markers, cancers, cardiovascular items, pharmacogenetic items, etc. In some embodiments, the item of interest may be selected from, but not limited to antibodies to HCV, antibodies to HIV 1/HIV 2, antibodies to hepatitis B core antigen (HBcAb), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), Hepatitis B Surface Antigen (HBsAg), antibodies to Hepatitis B Surface antigen (HBsAb), alpha-fetoprotein (AFP), Total prostate specific antigen (Total PSA), Free PSA, Thyroid stimulating Hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), beta human chorionic gonadotropin (B-hCG), Free Thyroxine (Free T4), Free triiodothyronine (Free T3), Total T4, Total T3, Progesterone, Testosterone, Estradiol, Prolactin, vitamin B12 (B12), Folate, Glycated Hemoglobin, and Ferritin. In essence, almost anything can be the item of interest.  
     [0048] The structures and methods described herein may be employed in a number of different configurations. For the sake of clarity of understanding, the structures and methods will be discussed with respect to their employment in a DNA/RNA sample preparation, amplification, and detection analyzer which performs approximately 100 or more determinations of items of interest in a sample in an hour, or if the sample preparation is divided, approximately 300 or more determinations of items of interest in a sample in an hour. Alternately, the same structure may be used as an immunoassay analyzer or as both an immunoassay analyzer and DNA/RNA analyzer. It is to be noted that the structures and methods can be used in other employments, such as in analyzers which perform 600, 400, 200, 50, etc. determinations in an hour.  
     [0049] A number of structures may be joined together or integrated to meet individual needs, such as modifying the number of tests performed in a given time period (throughput), tailoring the items of interest to be determined, etc. For example a number X of structures which perform Y determinations in a given hour may be connected such that the connected structures perform XY determinations in an hour. If desired, the resources of the structures may be allocated in a manner substantially similar to that disclosed in co-pending U.S. patent application Ser. No. 09/041,352 filed on Mar. 12, 1998. That application is assigned to the assignee of the present case and the disclosure thereof is incorporated herein in its entirety.  
     [0050] In other embodiments, one or more structures may be operatively connected with another analyzer, such as an immunoassay analyzer (e.g. disclosed in U.S. Pat. No. 5,795,784 referenced below), a blood analyzer (e.g. disclosed in U.S. Pat. No. 5,891,734 referenced below), and the like.  
     [0051] It is to be noted that all such structures may perform all similar determinations of items on interest in substantially the same way. For instance, all determination process steps for all similar items of interest may be performed within the same time frame, such as 36 seconds, irrespective of the number of determinations to be performed by the given structure. These structures may include common elements, such as reagents, disposable articles, other elements, such as fluids and the like, delivery technologies, determination step performance mechanisms, software, etc.  
     [0052] In other applications, the structure may be joined, e.g. with a conveyor system and the like, along with supporting hardware and software, such that the structure can be used with different structures or analyzers, such as clinical chemistry or hematology analyzers and the like, in the same setting. This conveyor system may move samples among the structures such that different determinations can be made with respect to one sample. Also, while operation of the structure is described herein with respect to only one structure, for the sake of clarity, it is to be remembered that multiple structures can operate in the same or in different fashion, either simultaneously or at different times. Furthermore, steps of one method of operation can be combined with steps of another method of operation to arrive at yet more methods of operation.  
     [0053] Any of the structures or methods described herein may be combined, in any suitable fashion, with the structures or methods or portions thereof described in currently available literature, such as the following United States Patents. As all of these patents are assigned to the assignee of the present case, the disclosures of those patents are incorporated herein in their entirety. The United States Patents are: U.S. Pat. Nos. 5,468,646, 5,536,049, 5,543,524, 5,545,739, 5,565,570, 5,669,819, 5,682,662, 5,723,795, 5,795,784, 5,783,699, 5,856,194, 5,859,429, 5,891,734, and 5,915,583.  
     [0054] Construction of structures described herein is intended to analyze specimens for various items of interest in a cost-effective way. The structures allow a user to supply a sample to the structure, to have the structure process, e.g. incubate, prepare, lyse, elute, analyze, read, etc., the sample and to have the structure report a result of the process. Structure sub-components include apparatus and methods of mixing, aspiration and dispense of materials, such as samples and reagents, incubation, chemistry separation, and detection, just to name a few. In general terms, structure construction implementation for chemistry automation may be driven by many factors such as desired patient sample addition methods, reagent addition methods, throughput (number of determinations per given time period), contamination reduction methods, detection methods, degree of mixing, and incubation temperature and duration needs.  
     [0055]FIG. 1 discloses a structure  1   a  amenable to a relatively decreased throughput, such as about 1 determination per every 1.5 hours, environment. The structure  1   a  comprises a first container  1  removably placed in a base  2 . In some embodiments, the base  2  may have a construction substantially similar to constructions of the process path disclosed in above-referenced U.S. Pat. No. 5,795,784, in which case, the structures illustrated in FIGS. 1 and 2 can be disposed at appropriate locations along the process path. Probe  3  is attached to a suitable prime mover such that the probe  3  can move in multiple directions, if desired. The probe  3  is fluidly connected at location  3   a  to suitable structures which enable the probe  3  to perform aspiration and dispense functions. These fluidic functions could be implemented with use of common pump (e.g. syringe, peristaltic, etc.) and valve technology, some of which is well understood today. The probe  3  can be moved by one of many means such as a Tecan gantry (Tecan RSP model series, Tecan Switzerland), an Abbott theta-Z robot (part number 78479, Abbott Laboratories, Abbott Park Illinois) or the like. Base  2  could be fabricated out of any desirable material, such as machined and coated aluminum and the like. In an exemplary embodiment, the base  2  is made with 6061-T6 aluminum with a MIL-A-63576 Type I finish. The first container  1  could be fabricated out of any desirable material, and may be molded out of a polyethlyne (DOW 30460M HDPE or Chevron 9512, for example) or polypropylene (Montel PD701N, for example), or polystyrene (Dow 666, for example). In the illustrated embodiment, the first container  1  is sized to contain an amount, such as about 7 mL, of fluid, such as sample and reagent. FIGS. 12A through 12P show alternative constructions of the first container  1 .  
     [0056] It is to be noted that the construction of the base  2  may be modified to accommodate or complement various constructions of the first container  1  as the base  2  provides features to accept first container  1  and to house a retractable magnet  4  shown in FIGS. 1 and 2.  
     [0057] Magnet  4  can be moved with respect to the first container  1  at selected times during performance of a given determination of an item of interest in a sample in the first container  1 . The movement of the magnet  4  can effect performance of a step in the determination process thereby allowing that step to be selectively automatically performed or avoided as desired. In one embodiment, the magnet  4  may be moved relatively proximate to the container to attract magnetically responsive particles within the first container  1  to a side wall of first container  1  thereby separating those particles which may be bound with a desired item of interest in a patient sample from the remaining patient sample or other contents of the first container  1 .  
     [0058] Before, during or after such magnet  4  induced separation, probe  3  may aspirate a portion of the first container  1  contents to waste/wash reservoir  10 . Subsequent dispense, separation, and aspiration steps may be employed to enhance the item of interest determination. During periods of the determination where magnetic separation is not desired, i.e. the magnetic separation step is avoided, magnet  4  may be moved relatively distally with respect to the first container  1  to reduce effects of the magnetic field of the magnet  4  on the first container  1  and its contents. If desired, magnetically responsive particles to which no item of interest is attached may be attracted to the side wall of the first container  1  while the remaining contents, possible containing an item of interest, of the first container  1  is removed from first container  1 , such as by the probe  3 .  
     [0059] In some embodiments, a thermal regulation device (heating and/or cooling)  7  can be provided with the base  2 . The device  7  may be manually or automatically removably connected with the base  2 , may be operated by an appropriate controller, such as a computer having memory running appropriate routines, and may utilize currently available thermal transfer means of conduction, convection, and/or radiation, etc. In one embodiment, thermally regulated (heated and/or chilled) air is moved with respect to the first container  1  to thermally regulate first container  1  contents in a desired manner.  
     [0060] At various times during performance of a given determination of an item of interest, a sample disposed in container  8  and reagent contained in container  9  may be added to first container  1 , such as by probe  3 . If multiple samples and/or reagents are desired, an array, such as a conveyor, a carousel, other movable arrangement, possibly recirculating, or the like, of multiple containers  8  and/or  9  could be provided. Containers  8  and  9  could be fabricated out of any suitable material, such as a polymer like polystyrene (DOW 666), high-density polyethylene (DOW 30460M HDPE or Chevron 9512) respectively, and the like.  
     [0061] To increase preservation of the contents of either container  8  or  9 , a cover  30  (FIG. 5C), substantially similar to the cover disclosed in U.S. Pat. No. 5,795,784 referenced above, could be added to either container  8  or  9 . The cover  30  may be made from any suitable material, such as Lexington Medical 3481005 EPDM, Abbott EPDM (Ashland, Ohio) and the like. Some constructions for containers  8  and  9  and associated covers can be found in U.S. Pat. No. Des. 401,697, U.S. Pat. No. Des. 401,699, and U.S. Pat. No. Des. 397,938 respectively, referenced above. A method for fitting a container such as container  8 , to other containers or a carrier is described in commonly owned U.S. Pat. No. 5,915,583.  
     [0062] Once sample and/or reagent is added to first container  1 , probe  3  may be washed, i.e. likelihood of exposure to a contaminant is reduced, by moving the probe  3  to waste/wash reservoir  10  for a fluid rinse of the probe  3 . In other embodiments, probe  3  could be modified to incorporate a disposable tip, such as the pipettor tip disclosed in U.S. Pat. No. 5,232,669 (assigned to the assignee of the present case and incorporated herein in its entirety by this reference). After intended use of the pipettor tip, the tip may be ejected from a fluidic/transport interface with the probe  3  to waste. Another example of a disposable tip  28  is illustrated in FIG. 5F.  
     [0063] A bore  6  is disposed on the base  2  to accommodate a detector, such as a photomultiplier tube, a photodiode and the like. In the illustrated embodiment, the bore  6  is located opposite magnet  4  in a similar fashion to the like structures disclosed in U.S. Pat. No. 5,795,784. Thus, similar operations, such as detection of chemiluminescence or other signal generated by a label, such as a fluorophore and the like, are possible.  
     [0064] A mixer  5 , illustrated in FIG. 2, is also provided on the base  2 . The mixer  5  is coupled to a driver  5   a  that applies force to the mixer  5 , possibly inducing an orbital motion on the first container  1  thereby causing mixing of first container  1  contents at desired times. The base  2  is constructed to limit first container  1  degrees of freedom important to the mixing process. Base  2  may include a lid to assist in controlling degrees of freedom important to the mixing process. FIG. 13 shows an alternate construction of mixer  5 . An additional embodiment of a suitable mixer is disclosed in U.S. Pat. No. 5,795,784.  
     [0065] If desired, the structure  1   a  shown in FIG. 1 can be modified to perform a larger number of determinations, such as about 100, in a given time period, i.e. a relatively increased throughput environment. The structure  1   a  could be operatively connected with one or more additional structures  1   a , each of which possessing one or more of the probe  3 , magnet  4 , mixer  5 , bore  6  for a detector, and the thermal regulation device  7 . In this embodiment, the multiple structures  1   a  permit selective activation of magnet  4 , detector  6 , heat/cooling elements  7 , mixer  5 , sample and reagent aspirations and dispenses, etc. at desired times during the determination process, viz. the steps executed by those elements are selectively automatically performed. With this arrangement, a determination of an item of interest in a sample can be conducted over more than one position or with more than one structure  1   a , thereby allowing at least two samples to be processed substantially simultaneously.  
     [0066] To streamline operative connection of multiple structures  1   a , a transport system, such as a conveyor (bounded or endless), a carousel or the like, could be used to move first container  1  from one structure  1   a  to another. The transport system may be substantially similar to the process path disclosed in the above-referenced &#39;784 patent. Depending on location of the structure(s)  1   a , the transport system and/or the individual structures can be constructed to provide only the functions desired to be performed at a given time in a determination. For example, a relatively large number, such as 100, structures  1   a  could be operatively connected together and only a subset, such as 5, of the structures  1   a  may include a mixer  5 .  
     [0067]FIGS. 3 and 18 show a structure  1   b  essentially comprising a plurality of structures  1   a  located substantially adjacently. In this embodiment, containers  1  are loaded substantially automatically onto a first process path  11  from a container loader and transport  35  illustrated in FIG. 9. Alternately, first container  1  could be loaded manually or automatically in a fashion described in the &#39;784 patent. Containers  1  are moved, possibly one position every selected time interval, such as every 36 seconds, through the first process path  11  to various locations along the first process path  11  where various operations, such as reagent addition, sample addition, incubation, mixing, washing and the like, are selectively automatically performed according to requirements of the intended format or protocol of the determination being performed. In an exemplary embodiment of the structure  1   b , the first container  1  is moved approximately 1.2 inches along the first process path  11  about every 36 seconds.  
     [0068] The first process path  11  includes at least one temperature controller or heater to keep the first process path  11  at a desired temperature. The first process path  11  may be kept at one temperature or any desired number of temperatures, such as with multiple heaters. In one embodiment, the heater maintains the first process path  11  at about 37 degrees Celsius. In another embodiment, one portion of the first process path  11  may be maintained at about 37 degrees Celsius while another portion of the first process path may be maintained at about 70 degrees Celsius.  
     [0069] Various methods may be implemented to heat the first process path  11  to at least one temperature while isolating the container  1  maintained at the least one temperature from other temperatures. For example, in one embodiment, the first process path  11  may be used to perform a first incubation, such as lysis for about 20 minutes at about 37 degrees Celsius, and a second incubation, such as elution for about 20 minutes at about 50 degrees Celsius, with container  1 . Container  1 , being used for both lysis and elution on the first process path  11 , can be thermally isolated from the second temperature while the container  1  is exposed to the first temperature, and vice versa.  
     [0070] If the first process path  11  were made of a suitable material, such as aluminum and the like, and if the first process path  11  were heated, e.g. conductively, to the first temperature or the second temperature at an appropriate time, a member may be introduced to thermally insulate portions of the first process path  11  exposed to the first temperature from portions of the first process path  11  exposed to the second temperature. This member may be an insulating material, a physical barrier or the like. The member may be actively cooled or heated based on temperature conditions measured at the first process path  11  portions specific to the first temperature, e.g. 37 degrees Celsius, and specific to the second temperature, e.g. 50 degrees Celsius, thereby limiting exposure container  1  to the first or second temperature, as appropriate.  
     [0071] In another embodiment, the first process path  11  is maintained at a first temperature, for example 37 degrees Celsius. At a portion of the first process path  11 , where it is desired to maintain a second temperature, for example 50 degrees Celsius, at least one other thermal energy source, such as an IR source and the like, may be thermally coupled with the first process path  11  to provide a desired amount of heat to the relevant portions of the first process path  11  at times required. Contents present in container  1  may experience a thermal rise to the second temperature during exposure to IR source followed by a thermal degradation to the first temperature as the container  1  is removed from exposure to the IR source.  
     [0072] In another embodiment of the structure  1   b  illustrated in FIGS. 10 and 11, once a first container  1  is placed on the first process path  11 , belt  36  moves first container  1  via engagement with pin  36   a  on the belt  36 . Prime mover  38  engages belt  36  via drive gear  40  and driven gear  41 . Prime mover mount  39  aligns prime mover  38  to driven gear  41  in the desired fashion.  
     [0073] Returning to FIGS. 3A and 3B, samples disposed in containers  8 , such as test tubes and the like, are loaded in container carriers  27  which are loaded onto input queue  17 . Examples of a sample container  8  and an associated container carrier  27  are shown in FIG. 6. The container  8  and the container carrier  27  may be substantially similar to the container disclosed in above-referenced U.S. Pat. No. 5,915,583 and U.S. Pat. No. Des. 401,697.  
     [0074] Input queue  17  may be constructed similarly to a sample handler like the currently available Abbott FPC Flexible Pipetting Center or the common structures described in the &#39;784 patent. An example of an input queue  17  is shown in FIG. 4 and comprises a conveyor system like that disclosed in the &#39;784 patent. The embodiment illustrated in FIG. 4 is constructed such that a structure, such as the structure  1   b  of FIGS. 3A and 3B, may be disposed in space  17   a  so that the input queue  17  and the structure  1   b  can cooperate. In this embodiment, sample input and output queues  17  and  17   b , respectively, may be disposed adjacent to each other offset by a local queue  17   c.    
     [0075] A bar code reader  25  is located adjacent the first process path  11  such that the bar code reader  25  can read a code associated with the container  8  and/or the container carrier  27 . The bar code reader  25  is used to identify a given sample located on the input queue  17  at a position accessible by pipettor  19 .  
     [0076] When the bar code reader  25  identifies a sample, pipettor  19  can transfer that sample from container  8  on the input queue to first container  1  located on the first process path  11 . Other items, such as reagents and the like, may be added to first container  1  by pipettor  19  and pipettor  12  in accordance with a given determination format. Reagents are stored in reagent handler  13  which may be similar to the reagent carousel disclosed in the &#39;784 patent. In an exemplary embodiment, pipettors  19  and  12  may add reagents to first container  1  at times specified in the “1 Tube DNA/RNA 20-20 Min Sample Prep Protocol, 1 Tube 1.5 hr PCR End Point Protocol” specified below.  
     [0077] In addition to pipettor  19  and  12 , dispense nozzles (not shown for clarity) fluidly connected with appropriate pumping mechanisms may add reagents from bottles  29 ,  31 , and  32  to first container  1  via fluid dispense nozzles. Containers  29 ,  31 , and  32  are shown in FIGS. 5E, 5A,  5 B and  19 . In one embodiment, container  31  contains solid phase microparticles, possibly magnetically responsive, which may require an agitator to homogenize the container  31  contents, i.e. resuspend the particles in a fluid medium. The agitator may be incorporated into a microparticle reagent handler  18  shown in FIGS. 3A and 3B. This re-suspension could be accomplished with commonly understood mixing fins, complementary container fins and/or fin motion among other methods. In a specific embodiment, resuspension of the particles within container  31  is achieved with a stir bar and associated apparatus also commonly understood in the field. Some or all containers described herein may be placed on the structure  1   b  shown in FIGS. 3A and 3B. The contents of the containers may be preserved with use of reagent seal  30  shown in FIG. 5C and/or with use of refrigeration. To provide additional flexibility in dispensing reagents, reagent dispense nozzles operatively associated with the first process path  11  may be integrated with transport mechanisms to allow reagents to be dispensed at any desired position on the first process path  11 .  
     [0078] Sometimes, it may be desirable to mix or to agitate the contents of first container  1 . Mixing of first container  1  contents along first process path  11  may be selectively automatically performed at an selected time by a mixer  5 , such as the mixer  5  shown in FIG. 13. In this embodiment, first container  1  is operatively engaged via feature  44  which is, in turn, operatively coupled to gear train  43 . Gear train  43  is configured to induce motion, e.g. orbital, circular or other, to first container  1  when rotated by prime mover  42 . In one embodiment, mixing occurs at times specified in the “1 Tube DNA/RNA 20-20 Min Sample Prep Protocol, 1 Tube 1.5 hr PCR End Point Protocol” specified below.  
     [0079] In an embodiment where pipettors  19  and  12  are configured for use with disposable pipettor tips  28  shown in FIGS. 5F and 19, transport and loading of a tip  28  or a group of tips  28  may be accomplished with loader and transport mechanism  33  shown in FIG. 7, loader and transport mechanism  34  shown in FIG. 8 or other equivalent arrangements.  
     [0080] After engagement of a tip  28  by either pipettor  19  or  12 , liquid level sensing (executed by any currently available method), aspiration from selected container(s), and dispense to first container  1  occurs. Pipettor  12  or  19  may include an apparatus which can detect a liquid level and/or temperature. This apparatus may include, but is not limited to, photo optics, capacitive members, IR, sonar, or other wave form generators. After dispense, tip  28  is washed with liquid at wash station  23  thereby reducing exposure to a contaminant. Subsequent additions to first container  1  may occur in similar fashion, as desired. After all desired additions to first container  1  have been completed, first container  1  contents may be is aspirated or otherwise removed from first container  1  and dispensed or transferred to desired locations where other functions, such as genetic sequencing, a pharmacogenetic test and the like, can be performed. Then, the tip  28  may be removed from pipettor  12  or  19  and disposed to tip  28  waste  24 , thereby reducing exposure to a contaminant. By using a single tip  28  for multiple reagent and singular sample or prepared sample manipulations can reduce solid waste and can provide reduced cost while maintaining desired levels of contamination reduction. Similar steps may be performed with the pipettors  12  or  19  even if they do not include a tip  28 .  
     [0081] Mixing with mixer  5  or other motions imparted to first container  1  may induce unintended distribution, e.g. aerosoling, of fluids contained in first container  1 . FIG. 14 shows feature or port  45  integrated into first process path  11  at appropriate locations. Port  45  is fluidly connected with a fluid pressure source, such as a negative fluid pressure source like a vacuum and the like, that draws air flow above first container  1  away from adjacent containers  1  on first process path  11  to a more desirable location. In this method, undesirable airborne contaminants may be routed to controlled locations.  
     [0082] Washing of microparticles used in some methods performed by the structures  1   a  and  1   b , viz. immunodiagnostic and/or PCR sample preparation methods, may utilize removal, evacuation or pipetting of unbound or bound microparticles from first container  1  and/or other constituents of the first container  1  contents, such as if some of the first container  1  contents were attracted to and held by magnet  4 .  
     [0083] To perform this washing, at least one wash zone  50  is located at an appropriate position along first process path  11 . Within a wash zone  50  resides a probe  49 , shown in FIG. 16, constructed to automatically evacuate or pipette first container  1  contents, such as unbound or bound microparticles from first container  1 . More than one probe  49 , such as 4, may comprise a single wash zone  50 . Washing steps, e.g. magnetic separation, aspiration, dispense, are further described in the &#39;784 patent.  
     [0084] Where contamination is a concern, such as with DNA/RNA determinations, probe  49  can be formed with an outer tube  46  and inner tube  47  as shown in FIG. 15. Outer tube  46  may be held substantially concentrically with respect to inner probe  47  via member  46   a . In some embodiments, the member  46   a  may function as a fluid conveying conduit. In one embodiment, outer tube  46  is fluidly connected to a wash fluid source and inner tube  47  is fluidly connected to a vacuum source routed to waste. The wash fluid may be used for many purposes, such as to chemically wash unbound particles from particles bound to an item of interest held in first container  1 , and also to remove undesirable items, i.e. contamination, from inner tube  47  after inner tube  47  comes into contact with fluid, such as fluid in the first container  1 , during evacuation.  
     [0085] To improve methods of attracting microparticles to walls of first container  1 , the microparticles within the first container  1  may be exposed to a magnet station comprising two magnets disposed adjacent to the first container  1  along opposite sides of the first container  1 .  
     [0086] Microparticles attracted to side wall(s) of first container  1  can be resuspended at any time, such as during washing, via a suitable device, such as mixer  5  shown in FIG. 13. Alternately, a probe  3  or  49  can be used to effect fluid and/or solid resuspension within the first container  1  by appropriate movement of fluid within the first container  1 . In such an embodiment, fluid, such as wash solution, is dispensed from a probe  3  or  49  such that a single or plurality of fluid streams is directed at a position within the first container  1 , such as a vertical wall thereof, where relevant fluid and/or solid material to be resuspended is expected to reside. In this manner, the material to be resuspended in the first container  1  may be dispersed within the first container  1  as shown in FIG. 17.  
     [0087] After processing of first container  1  contents is complete according to the selected format or protocol, the first container  1  contents is moved from first container  1  and placed into second container  15  shown in FIG. 3. Material, such as reagent, additions to second container  15  occurs via pipettor  12 . Second container  15  is then sealed with sealer  21 .  
     [0088] Where relatively quick heating and cooling rates of the second container  15  are desired, the second container  15  can be constructed to sustain relatively quick thermal energy transfer rates by using a relatively large heated surface to second container  15  contents volume ratio and/or a relatively thin wall(s) of the second container  15 .  
     [0089] To facilitate transfer of first container  1  contents to second container  15  in an automation fashion, second container  15  can be constructed with a first chamber and a second chamber with a first chamber opening being relatively larger than a second chamber opening. Pipettor  12  can enter and can fill the first chamber with first container  1  contents and other reagents. Then, the first chamber opening may be sealed with sealer  21 . The relatively smaller second chamber opening may restrict the contents of the first chamber from moving to the second chamber. Alternatively, the first chamber opening may be sealed by sealer  21  to a first level called a “soft-seal” prior to transfer of the container to spinner  22 . In this case, after removal of the second container  15  from spinner  22 , the first chamber opening may be sealed by sealer  21  to a second level different than the first level.  
     [0090] Second container  15  is transported to a spinner device  22  that moves the second container  15  such that contents of the first chamber are displaced to the second chamber by centrifugal force. After the contents of the first chamber have moved to the second chamber, second container  15  is removed from spinner device  22  to a heat transfer device for further processing. Alternately, filling of second container  15  to its second chamber can be achieved by force induced by pressure from fluidics coupled to pipettor  12 , or, pipettor  12  can enter the second chamber of second container  15  and thereby fill the second chamber.  
     [0091] Although capillary tube or tubes having capillary like construction are amenable to desirable heat transfer rates, filling such tubes typically involves force or centrifugation to move liquid into the tube. In another embodiment, second container  15  comprising assembly  15   c , illustrated in FIGS. 27A through 27F, may be used. In this embodiment, second container  15  is accepts contents through opening  57 . The orifice of opening  57  of second container  15  is relatively larger than a capillary tube to allow for automated pipetting of contents into second container  15  without any secondary operations, such as centrifugation. Prior to further DNA amplification, second container  15  may be sealed to reduce contamination. Seal  15   b  engages second container  15  to provide contamination reduction and evaporation control. An outer wall  58  of seal  15   b  is relatively smaller than an inner wall  59  of second container  15  such that, when engaged with second container  15 , contents in second container  15  can displace around outer wall  58 . This displacement of contents increases heat transfer to liquid area ratio thereby providing for relatively rapid heat transfer. In some embodiments, outer wall  58  can include fins (not shown) such that the fins engage second container  15  inner wall  59  to position seal  15   b  substantially concentrically with respect to second container  15  thereby providing for substantially uniform displacement of contents around the outer wall  58  of seal  15   b  and for substantially uniform heat transfer to the contents.  
     [0092] Second container  15  and seal  15   b  are matable to form assembly  15   c  shown in FIGS. 27C and 27F. This assembly  15   c  can be transferred to a second process path or thermal cycling/detection module  16  for further processing.  
     [0093] In one embodiment, the steps of transporting the second container  15  to the spinner device  22  occur after pipettor  12  adds up to three reagents and sample to second container  15 . A robot then moves second container  15  to a second process path or heat transfer/detection apparatus  16 . The apparatus  16  may bring the second container  15  to a temperature the same as or different from a temperature(s) to which the first process path brings the first container  1 .  
     [0094]FIGS. 3A and 3B illustrate one construction of the heat transfer/detection apparatus  16  comprising  112  heat transfer/detection modules  16   a  such that throughput of samples prepared on first process path  11  is compatible with PCR processing times of approximately one hour to yield a structure throughput of approximately 100 tests per hour. Heat transfer/detection apparatus  16  can be used for isothermal reactions, thermal cycling, integrated heat transfer and detection, among other processes. In some embodiments, heat transfer functions and the detection functions can be performed by separate structures, e.g. the apparatus  16  can comprise a hat transfer structure and a detection structure, which may be located adjacently, separately or in any appropriate fashion. After detection in apparatus  16 , second container  15  is automatically removed and discarded to waste by the robot or transferred to another detector for further determinations.  
     [0095] In the embodiment shown in FIGS. 3A and 3B, isolated sample preparation can be performed on first process path  11  and amplification and detection can be performed on the adjacent apparatus  16 . Here, these two processes are substantially separated such that contamination concerns specific to DNA/RNA chemistries may be reduced.  
     [0096] The first process path  11  for automated preparation of sample may be operatively connected to the apparatus  16  for amplification and detection by further apparatus such as the robot.  
     [0097] In some embodiments, the second process path  16  is a continuation of the first process path  11  thereby forming a single process path. In such an embodiment, any of the containers described herein may be used along the entire process path thereby eliminating the need to transfer from container  1  to container  15 . In other words, sample can be transferred from the sample container  8  to a single process container that is used to perform all the steps described herein.  
     [0098] There are a number of other possible modifications to the structures  1   a  and  1   b . In one modification, first process path  11  in FIGS. 3A and 3B can include a process step performance lane, such as first process path  11 , where a process step is selectively automatically performed, and a process step avoidance lane where the process step is selectively automatically avoided, possibly located to avoid a wash zone  50 . First container  1  containing the reaction mixture may be selectively automatically positioned in a selected one of the process step performance lane or the process step avoidance lane based on selected format or protocol similar to the manner described in the &#39;784 patent.  
     [0099] In other modifications, second container  15  could be a capillary tube, a tube possessing capillary tube characteristics, a reaction vessel described in U.S. Pat. No. Des. 401,700, a reaction tube, such as that supplied by Cepheid of Sunnyvale, Calif., a tube similar to first container  1 , and the like. Heat transfer/detection apparatus  16  could utilize Peltier, microwave, resistive, forced air and/or liquid heating/cooling technologies. Modules  16   a  could also utilize Peltier, IR, microwave, resistive, forced air and/or liquid heating/cooling technologies, and may be substantially similar to the thermal cycler and/or detector components of the Smart Cycler™ system supplied by Cepheid (Sunnyvale, Calif.), the Tetrad™ or PTC-100™ systems supplied by MJ Research, INC (Waltham, Mass.), the Sprint™ system supplied by Hybaid (Franklin, Mass.), the Multigene™ system supplied by Labnet International (Woodbridge, N.J.), the RoboCyler™ 40 or 96 systems supplied by Stratagene USA (La Jolla, Calif.), the 480, 9600, or 9700 systems supplied by Perkin-Elmer (Foster City, Calif.), and the like.  
     [0100] Further modifications of the structures  1   a  and  1   b  are possible. The following examples of such modifications utilize common reference characters for similar structures.  
     [0101] In another structure  1   c  shown in FIG. 20, heat transfer/detection apparatus  16  can be integrated into first process path  11  as shown in FIG. 20. Here, first container  1  remains on first process path  11  while passing through thermal zones amenable to the desired format.  
     [0102] In an additional structure  1   d  shown in FIG. 21, the first container  1  is transferred to second container  15  and, subsequently, second container  15  passes through thermal zones amenable to desired format. Thus, a portion of a thermal reaction can be implemented in second container  15  processing line  15   a  prior to transfer of the second container  15  to heat transfer/detection apparatus  16 .  
     [0103] In another structure  1   e  illustrated in FIG. 22, the second process path or heat transfer/detection apparatus  16  can include a plurality of individually controlled second process sub-paths or heat transfer/detection paths  16   b . Each of the heat transfer/detection paths  16   b  may be dedicated to a particular item of interest in a manner substantially similar to the construction of the Abbott Prism® instrument.  
     [0104] In an additional structure  1   f  depicted in FIG. 23, first container  1  contents processing can be preformed and the processed first container  1  contents transferred into a reaction vessel or tray  52 , such as a multiple well (e.g. 96 wells) tray filled with desired reagents. The structure if may also include a bypass region  56  on the first process path  11 , as described in the &#39;784 patent. The tray may be sealed and moved to an output queue  54  for transfer, either manual or automatic, to further apparatus such as heat transfer/detection apparatus  16 . In this modification, further methods may be employed to improve customer lab workflow by sorting samples by desired assay in a sample handling queue  17  prior to further processing. This allows for consolidation of heating and cooling devices, such as the number of modules  16   a  within the heat transfer/detection apparatus  16 , needed to process chemistry requiring different heating and cooling protocols for each assay.  
     [0105] The structures described herein and their use may be optimized, for example, the structures may be adjusted such that number of determinations in a given time period are increased, by allocating items such as determinations to be performed, samples, reagents, containers, etc., across elements of the structure(s).  
     [0106] For example, an operator loads samples on the sample handler  17  of the structure in any order. To reduce cost per determination or to improve structure reliability, among other things, the number of items present in a structure may be reduced. Some determinations, for example DNA/RNA amplification and detection, require heating and cooling protocols that may vary from determination to determination. This may complicate cost and/or item reduction. To achieve these reductions, items may be allocated across elements of the structure(s).  
     [0107] In the embodiments discussed herein, a determination method may consist of a number, such as three, of processes. In one employment, a determination comprises a first process, a second process and a third process. The first process may be common to all determinations, such as DNA/RNA sample preparation, sample incubation, immunodiagnostic sample preparation and determination and the like. The second process, for example, amplification and the like, may be specific to a given determination. The third process, for example, detection, may be either common to all determinations or specific to a given determination.  
     [0108] To allocate items across elements of the structure(s), samples are identified and then grouped by commonality in second and third processes. For example, one DNA/RNA assay may be processed according to one protocol, such as Protocol A described below, in one module  16   a ,  16   b ,  16   c  or  16   d  while another DNA/RNA assay may be processed according to another protocol, such as Protocol B described below, in another module  16   a ,  16   b ,  16   c  or  16   d . By supplying samples, selected by common second and third processes, from sample handler  17  to process path  11 , allocation of modules  16   a ,  16   b ,  16   c  or  16   d  to specific determination(s) may be achieved while reducing the number of modules  16   a ,  16   b ,  16   c  or  16   d  and containers  52  needed, while increasing throughput.  
     [0109] Sample sorting may comprise identifying sample information by reading a bar code on container  8  held by the sample handler  17  with a barcode reader. The containers  8  may then be sorted (mechanically) with other containers  8  within a given carrier  27  and then carriers  27  may then be sorted with other carriers  27  in the sample handler  17  by determinations having common second and third processes. After sorting, samples from containers  8  are transferred to container  1  by pipettor  19 . Alternately, sample sorting may be achieved by pipettor  19  selectively transferring sample from container  8  to container  1  on process path  11  based on predetermined, sorted order.  
     [0110] Once the sample is in the container  1  on the process path  11 , the first process comprising the determination method is performed. After the first process is finished, depending on the particular structure used, the second and/or third processes may occur in either the process path  11 , in one or more modules  16   a ,  16   b ,  16   c  or  16   d , or in separate apparatus.  
     [0111] By sorting or grouping samples according to common second and/or third process, an optimal number of modules  16   a ,  16   b ,  16   c  or  16   d  can be allocated to determining a given item of interest, viz. the greatest number of determinations of a given item of interest can be discerned, associated samples can be suitably sorted, and elements or items of or in the structure(s), such as containers, reagents and the like, can be appropriately duplicated over two or more modules  16   a ,  16   b ,  16   c  or  16   d  on a given structure(s). Similarly, two or more modules  16   a ,  16   b ,  16   c  or  16   d  can be duplicated based on specific determination protocols.  
     [0112]FIG. 22 shows another structure  1   e  where modules  16   b  can be duplicated according to sample sorting outcomes. FIGS. 23 and 24 show other structures  1   f  and  1   g  where modules  16  can be located exterior to the structure(s). Here, sorted samples can be duplicated across multiple modules  16  exterior to the structure(s)  1   f  and  1   g.    
     [0113]FIG. 20 shows another structure  1   c  where module  16  is integrated into process path  11 . Sample sorting here allows for process path  11  to be programmed for one determination for a first period of time and then be programmed for another determination for a second period of time.  
     [0114] In applications involving sorting samples by determination in sample handling queue  17  prior to further processing, it may be desirable to form relatively small groupings. The grouping size can determine the size of tray  52  and its corresponding heat transfer/detection apparatus  16 . In a structure  1   i  depicted in FIG. 26, samples may be sorted by determination into relatively small groupings including about twelve samples. The tray  52  and thermal cycling/detection module  16   c  within thermal cycling/detection module  16  are both configured to accommodate groupings of twelve with module  16   c  providing individual control of each grouping of twelve. The structure  1   i  may reduce the number of thermal cycling/detection modules  16   c  required to maintain desired throughput.  
     [0115] Additional enhancements, such as with software controlling the structure, can be provided to manage test distribution lists, to generate reagent load maps, to make reagent loading suggestions, and to manage data.  
     [0116] In an further structure  1   g  shown in FIG. 24, first container  1  contents preparation can be preformed and the prepared first container  1  contents can be transferred into another container or tray. The container is moved to an output queue for manual or automatic transfer to further apparatus that performs reagent addition, heat transfer, and detection.  
     [0117] In an additional structure  1   h  depicted in FIG. 25, samples do not need to be sorted in sample input queue  17 , and the number of thermal cycling/detection modules  16   d  required is reduced. In this structure  1   h , second container  15  is transferred to thermal cycling module  16   d , each module  16   d  being individually controlled and each having a detector. Module  16   d  may thermally transfer second container  15  through a plurality, such as about two or three, thermal zones within a carousel over a number of positions. One position on the carousel contains a detector. Module  16   d  is designed to accept additional containers  15  sequentially while other containers  15  are being processed within module  16   d . Alternately, module  16   d  can be fully loaded with containers  15  and all containers can be processed substantially simultaneously.  
     [0118] Other embodiments of the module  16   d  are illustrated in FIGS. 30A, 30B,  31 ,  32 A and  32 B. Common reference numbers are used to indicate similar structures in FIGS. 30A, 30B,  31 ,  32 A and  32 B. These other embodiments of the module  16   d  can be used for thermal amplification and detection of PCR products, for example.  
     [0119] A tray  70  has at least one compartment or well  71  where thermal amplification can occur. While the embodiments of FIGS. 30B and 32B includes 8 wells  71 , the number of wells  71  can be modified as desired. The well  71  can be numbered and may be bar coded to facilitate identification. In this manner, well  71  position, contents, etc. can be checked by machine, such as with optics. In some embodiments, the tray  70  may be a disposable item easily removed from the associated structure.  
     [0120] A well  71  may be bounded on at least one side by a divider  72  to reduce exposure of contents of a well  71  to a contaminant. To further reduce exposure to a contaminant, the well  71  may be removably covered or sealed.  
     [0121] The tray  70  is operatively connected with a motor  76  (FIG. 31), such as a stepping motor, a servo motor or the like controlled by a microprocessor and the like, by a drive shaft  73  thereby providing for desired, controlled rotation of the tray  70 .  
     [0122] Container  8  contents can be transferred from the first process path  11  to the well  71  for amplification and detection. To provide desired thermal exposure of the tray  70  and the well  71 , at least one heater  74  is thermally associated with the tray  70 . If multiple or different thermal exposures are desired, then an appropriate number of heaters  74  can be included. As shown in FIGS. 30B and 32B, four (4) heaters  74  are disposed in thermal association with the tray  70  thereby providing four different temperatures or different thermal exposures. The heater  74  may utilize electric, microwave, Peltier effect, forced air or similar technology.  
     [0123] The heater  74  may operate such that the well  71  is at a desired temperature prior to or after addition of contents to the well  71 . In some embodiments, the heater  74  may be separated from the tray  70  such that the tray  70  is operatively connected with the heater  74  either prior to or after addition of contents to the well  71  on the tray  70 .  
     [0124] As the tray  70  rotates, the well  71  and its contents are exposed or brought to the temperature provided by the adjacent heater  74 . As thermal variations may be cyclical, i.e. repetitive of a given pattern, rotation of the tray  70  can bring the well  71  and its contents to desired temperature(s) in desired sequence for a desired time period. Thus, the well  71  and its contents can experience consecutive, well-defined temperature zones as the tray  70  rotates. Each heater  74  may correspond to temperatures specific to a given reaction, such as melt, annealing, extension, etc., defined by the particular determination being performed.  
     [0125] A time period during which a given well  71  is located adjacent a given heater  74  is determined by the rotational speed of the tray  70 . In some utilizations, a number of rotations or step-wise movements of the tray  70  may be proportional to a number of cycles performed by a currently available thermal cycler. Rotational speed of the tray  70  may be controlled such that the well  71  is positioned adjacent a heater  74  for a specified length of time. For example, a first heater  74  may bring the well  71  to a temperature capable of dissociating, or melting, double stranded DNA strands. A second heater  74 , adjacent the first heater  74 , may bring the well  71  to a temperature that induces association of complementary strands, such as a target and a primer, or a target and a probe. The second heater  74  or another heater  74  may be used to allow enzymatic polymerase elongation of the primer, and the well  71  is positioned adjacent that heater  74  for a time sufficient for the reaction to finish. By adjusting tray  70  rotational speed, thermal “area,” i.e. the area in which the heater  74  can bring the well  71  and its contents to a temperature associated with the heater  74 , of the heater  74  and temperature values associated with the heater  74 , optimal thermal cycling parameters for a certain assay may be accomplished.  
     [0126] Once the desired thermal exposure of the well  71  is complete, the item of interest present in the well  71  can be detected by detector  75 . If the well  71  were sealed, then the seal may be removed or, alternatively, the seal may be made of a material that allows optical transmission so that detector  75  can monitor the well  71  and detect the item of interest, if present. The detector  75  may also read a bar code associated with the tray  70  or the well  71 .  
     [0127] The detector  75  may be used in a dynamic (real time) mode, such as to detect, in real time, PCR products by reading the well  71  as it moves with respect to the detector  75 . In some embodiments, the detector  75  may read the well  71  every n times the well  71  encounters the detector  75 . The number n may be determined to allow for comparing status of the well  71  with a predetermined threshold at a predetermined time(s). The detector  75  can be used for static, end point reads.  
     [0128] The detector  75  may be stationary with respect to the tray  70  or may move with respect to the tray  70 . If multiple trays  70  are present, then multiple detectors  75 , such as one detector  75  for each tray  70 , may be used. Fiber optics may be used to channel light from a well  71  to the detector  75 .  
     [0129] The detector  75  may use a light source to illuminate contents of a well  71  at a single or multiple wavelengths, thereby accommodating multiplex detector  75  data reduction of multiple wavelength emission intensity at discrete wavelengths, for example. In some embodiments, the detector  75  may provide single or parallel detection of single or multiple wavelengths, such as fluorescence emissions from the well  71 .  
     [0130] Another module  16   h  is shown in FIG. 33. This module  16   h  includes a fluid conveying conduit  77  disposed within a block  78 . The conduit  77  may be formed as a coil  79  in the block  78 . The block  78  is constructed with suitable thermal energy conductive elements to form at least a first thermal zone  80 A having a first temperature and a second thermal zone  80 B having a second temperature different from the first temperature. With this construction, some portions of the coil  79  are in a thermal zone  80 A or  80 B different than other portions of the coil  79  while some portions of the coil  79  are in the same thermal zone  80 A or  80 B.  
     [0131] Container  1 ,  8  or  15  contents or fluid can be transferred from the first process path  11  to an inlet  81  of the conduit  77 . The fluid forced to flow from the inlet  81  through the coil  79  by suitable means, such as a pump, capillary action, etc. As the fluid flows through the coil  79 , the fluid encounters or is brought to different temperatures as it moves between thermal zones  80 A and  80 B.  
     [0132] The temperatures associated with the thermal zones  80 A and  80 B can be chosen to match temperatures of specific PCR amplifications. In this embodiment, a number of turns, or loops, comprising the coil  79  is equivalent to the number of cycles performed by a currently available thermal cycler. The fluid flow in the coil  79  is controlled such that the fluid resides in each thermal zone  80 A or  80 B a specified length of time. For example, one thermal zone  80 B may bring the fluid to a temperature capable of dissociating, or melting, double stranded DNA strands. The other thermal zone  80 A may bring the fluid top a temperature inducing association of complementary strands, such as a target and a primer, or a target and a probe. This same thermal zone  80 A may be used to allow enzymatic polymerase elongation of the primer. Of course, the fluid flow is adjusted to expose the fluid to a thermal zone  80 A or  80 B for a time period sufficient for the reaction to finish. A detector  75  is disposed adjacent the coil  79  to monitor status of the fluid within the coil  79  in a manner substantially similar to that described above.  
     [0133] Fluid corresponding to various samples may be introduced to the conduit  77  separated by suitable other fluid, such as air, a buffer and the like.  
     [0134] Any heat transfer/detection module can be used in apparatus  16 . For example, apparatus  16  can use methods described in U.S. Pat. No. 5,576,218, assigned to the assignee of the present case. The disclosure of the &#39;218 patent is incorporated herein in its entirety.  
     [0135] The module  16   a  shown in FIGS. 3A and 3B can provide thermal cycling of reaction contents in second container  15  with use of heated or chilled fluids as shown in FIG. 29. Fluid is stored reservoir  65  and heated or chilled by thermal controller  66 . Fluid is routed to module  16   a  through port  16   e  at desired times by metering fan or pump  67 . Heat transfer occurs between the contents in second container  15  and the heated or chilled fluid. The metered amount of fluid transferred to module  16   a  determines the time contents in second container  15  will remain at a given temperature. Evacuation of fluid from module  16   a  occurs through port  16   f  with use of valve  68  and/or additional pumps or gravity to container  65  or to waste. Given that thermal mass of second container  15 , second container  15  contents and metered fluid contained in container  65  are known, the temperature of a metered fluid interaction with second container  15  may be calculated and predicted thereby reducing a need for temperature control at the interface of the fluid with the second container  15 .  
     [0136] Different temperatures of contents in second container  15  can be achieved, e.g., by adding additional reservoir pumps and ports, such as port  16   g  shown in FIG. 29. To enhance performance of rapid heat transfer, second container  15  can be constructed as a pouch out of a thin polymeric film. Also, thermal element  69  may be positioned adjacent to and in contact with module  16   a  and controlled at a desired temperature.  
     [0137] Orientation of detector optics to second container  15  or  15   d , for example, may be accomplished in many ways, one such way being shown in FIG. 28. Second container  15   d  may include at least one first face  60  on a first axis plane, designated ‘YZ’, and at least one second face  61  on a second axis plane ‘XY’. An optical source  62  may be located adjacent to the first face  60  and an optical detector  63  may be located adjacent to a second face  61  opposite the first face  60  such that excitation of a label associated with an item of interest is induced by optical source  62  and emission of a signal, such as light, from the label is detected by detector or detector pair  63 . The relative position of a first axis plane is different from the second axis plane to provide an increased signal collection area. The detector or detector pair  63  may be a single photodiode, quadrant photodiode, diode array, photomultiplier tube, or any combination of these detection devices. Combining optics with heating elements can be done with use of transparent heating elements  64  mounted in transparent material, such as glass, the heaters being located adjacent to at least one of the second faces of the second container  15   d , and possibly lying on the second plane. In some embodiments, the optical source  62  may lie on a plane substantially orthogonal to the detector or detector pair  63 . In this optical configuration, second container  15   d  could be a reaction tube supplied by Cepheid of Sunnyvale, Calif., or be any reaction container configuration including but not limited to a substantially hemispherical, spherical, cubic, or tetrahedron shape.  
     [0138] It is to be noted that additional first container  1  contents preparation, immunodiagnostic, and/or determination processing modules may be connected together with a common robotic and/or system processor, such as a computer and the like. It should also be noted that the heat transfer/detection apparatus  16  could accept first container  1  contents or other sample, processed or not, from another process path not operatively coupled to the structures  1   a  through  1   i.    
     [0139] The described elements comprising the structures  1   a  through  1   i  may be selectively automatically and/or manually operated at desired times to accomplish a desired determination of an item of interest. The functions of the elements can be performed in any desired order any desired number of times to achieve desired results. The methods of operation and items, such as reagents and the like, used may be substantially similar to those described in U.S. Pat. No. 5,234,809, the disclosure of which is incorporated herein in its entirety.  
     [0140] The following example of a DNA/RNA sample extraction protocol and polymerase chain reaction (PCR) protocol illustrates such an application. The time periods, temperatures, volumes and elements (containers, solutions, reagents, etc.) used can be adjusted as desired. The position numbers correspond to the structure  1   b  of FIGS. 3A and 3B. However, the position numbers may also indicate the number of stepwise movements along a process path in the same manner as used to described the various assay formats in the &#39;784 patent.  
     [0141] 1 Tube DNA/RNA 20-20 Min Sample Preparation Protocol and 1 Tube 1.5 hr PCR End Point Protocol  
     Sample Prep  
     [0142] 0Seconds— 
     [0143] At Position 0: Instrument loads first container  1  onto first process path  11   
     [0144] 1-36 Seconds— 
     [0145] At Position 1: Pipettor  19  engages a disposable pipette tip  28 , aspirates magnetically responsive microparticles (about 0.1 ml) from container  31  in reagent storage area  18 , and dispenses those microparticles into first container  1  at Position 1. The disposable pipette tip  28  is washed with fluid in wash cup  23 . Pipettor  19  aspirates another reagent (about 0.05 ml), such as an internal control and the like, from a container located in reagent handling area  13 , dispenses that reagent into first container  1 , and disposable pipette tip  28  is washed with fluid in wash cup  23  a second time. Sample (about 1 ml) disposed in container  8  is aspirated by pipettor  19  and dispensed into first container  1 . Disposable pipette tip  28  is removed from pipettor  19  and deposited in tip waste  24 . Alternately, the pipettor wash performed after microparticle dispense can be eliminated. In this case, microparticles and internal control are aspirated and dispensed into first container  1  substantially simultaneously or sequentially. Alternatively, a subset of or all liquid washes can be eliminated, in which case, microparticles, internal controls and sample may be aspirated and simultaneously and/or sequentially dispensed into first container  1 .  
     [0146] 37-72 Seconds— 
     [0147] At Position 2: A dispense nozzle coupled to first process path  11  is fluidically connected to a reagent container, such as reagent bottle  32  as shown in FIGS. 5B and 19, containing a lyse solution. About 6 mL of lyse solution is dispensed, either at room temperature or at about 37 degrees Celsius, to the first container  1 .  
     [0148] 73-108 Seconds— 
     [0149] At Position 3: Contents of first container  1  are mixed with mixer  5 . First container  1  contents are incubated at about 37 degrees Celsius.  
     [0150] 109-1260 Seconds— 
     [0151] At Positions 4 through 35: Continue incubation for about 19.8 minutes at about 37 degrees Celsius. First container  1  contents are mixed at about 648 seconds and at about 1224 seconds. Periodic mixing of first container  1  contents enhances reaction.  
     [0152] 1261-1296 Seconds— 
     [0153] At Position 36: Item of interest bound to microparticles are captured on side wall of first container  1  with magnet  4 .  
     [0154] 1297-1332 Seconds— 
     [0155] At Position 37: Elements comprising the wash zone  50  perform wash functions, described herein, comprising magnetic separation and aspiration and dispense of fluids with probe  49 . Specifically, microparticles are separated from the remainder of first container  1  contents by magnet  4  and probe  49  removes the unseparated first container  1  contents. A wash solution (buffer) is dispensed from the probe  49  into the first container  1 . Probe  49  is washed. Alternately, wash functions performed separately at, e.g. positions 36 and 37 can be combined at one position on first process path  11 .  
     [0156] 1333-1368 Seconds— 
     [0157] At Position 38: Probe  49  performs wash and dispense functions. Mixer  5  provides resuspension of microparticles into fluid, specifically wash solution #1 in this example, in the first container  1 . Alternately, resuspension of microparticles can be accomplished with appropriate fluid dispense into first container  1  as described above with respect to FIG. 17. Alternatively, functions performed at positions 36, 37, and/or 38 can be combined at one position on first process path  11 .  
     [0158] 1369-1404 Seconds— 
     [0159] At Position 39: Item of interest bound to microparticles are captured on side wall of first container  1  with magnet  4 . Elements comprising the wash zone  50  perform wash functions, described herein, comprising magnetic separation and aspiration and dispense of fluids with probe  49 . Specifically, microparticles are separated from the remainder of first container  1  contents by magnet  4  and probe  49  removes the unseparated first container  1  contents. Probe  49  is washed. Alternately, wash functions performed separately at, e.g. positions 36 and 37 can be combined at one position on first process path  11 .  
     [0160] 1405-1440 Seconds— 
     [0161] At Position 40: Probe  49  performs wash and dispense functions. Mixer  5  provides resuspension of microparticles into fluid in the first container  1 . Alternately, resuspension of microparticles can be accomplished with appropriate fluid dispense into first container  1  as described above with respect to FIG. 17. Functions performed at positions 36, 37, and/or 38 can be combined at one position on first process path  11 .  
     [0162] 1441-1476 Seconds— 
     [0163] At Position 41: Item of interest bound to microparticles are captured on side wall of first container  1  with magnet  4 . Elements comprising the wash zone  50  perform wash functions, described herein, comprising magnetic separation and aspiration and dispense of fluids with probe  49 . Specifically, microparticles are separated from the remainder of first container  1  contents by magnet  4  and probe  49  removes the unseparated first container  1  contents. A wash solution (buffer) is dispensed from the probe  49  into the first container  1 . Probe  49  is washed. Alternately, wash functions performed separately at, e.g. positions 36 and 37 can be combined at one position on first process path  11 .  
     [0164] 1477-1512 Seconds— 
     [0165] At Position 42: Probe  49  performs wash and dispense functions. Mixer provides resuspension of microparticles into fluid, specifically wash solution #2 in this example, in the first container  1 . Alternately, resuspension of microparticles can be accomplished with appropriate fluid dispense into first container  1  as described above with respect to FIG. 17. Functions performed at positions 36, 37, and/or 38 can be combined at one position on first process path  11 .  
     [0166] 1513-1548 Seconds— 
     [0167] At Position 43: Item of interest bound to microparticles are captured on side wall of first container  1  with magnet  4 . Elements comprising the wash zone  50  perform wash functions, described herein, comprising magnetic separation and aspiration and dispense of fluids with probe  49 . Specifically, microparticles are separated from the remainder of first container  1  contents by magnet  4  and probe  49  removes the unseparated first container  1  contents. A wash solution (buffer) is dispensed from the probe  49  into the first container  1 . Probe  49  is washed. Alternately, wash functions performed separately at, e.g. positions 36 and 37 can be combined at one position on first process path  11 .  
     [0168] 1549-1584 Seconds— 
     [0169] At Position 44: Probe  49  performs wash and dispense functions. Mixer  5  provides resuspension of microparticles into fluid, specifically wash solution #2 in this example, in the first container  1 . Alternately, resuspension of microparticles can be accomplished with appropriate fluid dispense into first container  1  as described above with respect to FIG. 17.  
     [0170] 1584-1620 Seconds— 
     [0171] At Position 45: Item of interest bound to microparticles are captured on side wall of first container  1  with magnet  4 . Elements comprising the wash zone  50  perform wash functions, described herein, comprising magnetic separation and aspiration and dispense of fluids with probe  49 . Specifically, microparticles are separated from the remainder of first container  1  contents by magnet  4  and probe  49  removes the unseparated first container  1  contents. Probe  49  is washed. Alternately, wash functions performed separately at, e.g. positions 36 and 37 can be combined at one position on first process path  11 .  
     [0172] 1621-1656 Seconds— 
     [0173] At Position 46: A pump, operatively associated with the first process path  11 , connected fluidly with a dispense nozzle, and fluidly coupled with the first process path  11 , and a reagent container, such as container  29  shown in FIGS. 5E and 19, induces dispense of a fluid, such as an elution reagent, to first container  1 . In one embodiment, about 80 μL of elution reagent is dispensed at ambient temperature or, alternately, at about 70 degrees Celsius.  
     [0174] 1657-2844 Seconds— 
     [0175] At Positions 47-76: First container  1  contents are incubated, for a period of about 19.8 minutes, in this example at about 37 degrees Celsius, or at a temperature substantially within the range of about 50 to about 70 degrees Celsius. Periodic mixing enhances reactions among elements of the first container  1  contents. Elution reagent releases the item of interest from the microparticles.  
     Assay  
     [0176] 2845-2880 Seconds— 
     [0177] At Position 77: At position 76, pipettor  12  engages a disposable pipettor tip  28 , aspirates a first reagent from a container in reagent storage area  13 , and dispenses that reagent into second container  15  on container processor line  15   a . The disposable pipette tip  28  is washed with fluid in wash cup  24 . Pipettor  12  aspirates a second reagent from a container in reagent handling area  13 , dispenses the second reagent into second container  15 , and disposable pipette tip  28  is washed with in wash cup  24 . A third reagent is aspirated into pipette tip  28  from a container in reagent handling area  13 , and the first container  1  contents containing the item of interest, about 50 μL, is aspirated from first container  1  in position 77 of first process path  11  to the pipette tip  28 . The third reagent and the aspirated first container  1  contents are dispensed from the pipette tip  28  into second container  15  and pipettor  12  ejects disposable pipette tip  28  to tip waste  24 . Alternately, the third reagent can be dispensed into first container  1  on first process path  11  at position 76 by pipettor  12  or by another dispense nozzle on the first process path  11 . In another embodiment, the first reagent and second reagent aspirations can be completed, without washing the pipettor  12  between aspirations, and the reagents can be dispensed into second container  15  substantially simultaneously. The volumes of each of the three reagents may be substantially within the range of about 10 to about 50 μL. If it were desired to detect more than one item of interest in a given sample, portions of the contents of first container  1  can be transferred to a corresponding number of containers  15 . These multiple transfers of first container  1  contents may occur from position 77 or, alternately, may occur from position 77 and subsequent position(s). If a relatively large number, such as about 15, of items of interest are to be determined from one sample, then multiple aspirations and dispenses can occur from container  8  and/or first container  1  by pipettors  19  and/or  12 .  
     [0178] 2881-2916 Seconds  
     [0179] Second container  15  is transported on the container processor line  15   a  to the sealer  21  where the second container  15  is sealed. The sealed second container  15  is transported to the spinner  22  where the contents in the upper portion of second container  15  are moved to the lower portion of second container  15 .  
     [0180] 2917-2952 Seconds  
     [0181] A robot engages second container  15 , and places the second container  15  in a heat transfer/detection module  16   a  where the second container  15  is exposed to a thermal cycle and the item of interest in the second container  15  is detected.  
     [0182] 2953-8352 Seconds  
     [0183] Assay Specific Thermal Cycling Protocols:  
     [0184] Second container  15  undergoes a thermal cycling protocol as specified. The following are a few examples of such a protocol.  
     [0185] Protocol A  
     [0186] 1. about 59 degrees Celsius for about 30 minutes. One cycle  
     [0187] 2. about 95 degrees Celsius for about 30 seconds, about 54 degrees Celsius for about 30 seconds, about 72 degrees Celsius for about 30 seconds. 4 cycles  
     [0188] 3. about 90 degrees Celsius for about 30 seconds, about 59 degrees Celsius for about 30 seconds, about 72 degrees Celsius for about 30 seconds. 46 cycles  
     [0189] 4. about 94 degrees Celsius for about 5 minutes, about 45 degrees Celsius for about 15 minutes, about 25 degrees Celsius for about 10 min. 1 cycle  
     [0190] Protocol B  
     [0191] 1. about 94 degrees Celsius for about 10 minutes. One cycle.  
     [0192] 2. about 94 degrees Celsius for about 1 minute, about 58 degrees Celsius for about 1 minute. 45 cycles.  
     [0193] 3. about 58 degrees Celsius for about 10 minutes, about 94 degrees Celsius for about 5 minutes, about 55 degrees Celsius for about 15 minutes, about 25 degrees Celsius and maintain.  
     [0194] Protocol C  
     [0195] 1. about 95 degrees Celsius for about 9.5 minutes. One cycle.  
     [0196] 2. about 95 degrees Celsius for about 30 seconds, about 59 degrees Celsius for about 1 minute. 41 cycles.  
     [0197] 3. about 95 degrees Celsius for about 3 minutes, about 25 degrees Celsius for about 10 minutes. One cycle  
     [0198] 8353-8388 Seconds  
     [0199] After completion of the particular thermal cycling protocol selected, the item of interest in the second container  15  is detected and the second container  15  is disposed. A result of the above steps is reported.  
     [0200] In any of the embodiments described herein, lysis may include use of induced electrical pulse(s) or sonication whereby such pulsing causes DNA/RNA to be exposed in undamaged form prior to binding. Electrical pulse(s) may also be used to reduce likelihood of contamination, such as contamination of sample to sample, reagent to reagent, sample to reagent, and/or reagent to sample.  
     [0201] In addition to the above-disclosed DNA/RNA method or protocol, the method performed by the structures  1   a  through  1   g  may be an immunodiagnostic method. For example, U.S. Pat. No. 5,795,784 lists various methods or formats that may be executed with the above-disclosed structures  1   a  through  1   g , possibly with appropriate modification. Furthermore, DNA/RNA extraction could be amplified and detected with the structures  1   a  through  1   g , or alternately transported to another structure  1   a  or a different structure, such as those disclosed in the &#39;784 patent and the like, for further processing. It is understood that first container  1  could be sealed by suitable means, if desired.  
     [0202] In another embodiment, the contents of first container  1 , after processing discussed above, can be transferred from Position 76 on the first process path  11  to an optical flow cell on the structure. The optical flow cell is substantially similar to that described in the following U.S. Pat. Nos. 5,589,394, 5,601,234, 5,631,165, 5,631,730, 5,656,499, 5,812,419, and 5,891,734. Those patents are assigned to the assignee of the present case and the disclosures thereof are incorporated herein in their entirety. The item of interest in the sample can be detected with the optical flow cell.  
     [0203] In a modification of this embodiment, sample directly from first container  1 ,  8 ,  15 , or another sample carrying vessel can be transferred to a sample receiving cups on the structure. The sample can be mixed and suitably incubated with a reagent containing a label. The reagent may be formulated such that the label encounters or passes through cell and/or nuclear membranes in the sample thereby permitting the label to bind or otherwise to become associated with the item of interest in the sample irrespective of where the item of interest is located within the sample. If the label encounters no item of interest in the sample, such as if no item of interest is present in the sample or if all items of interest in the sample are already associated with a label, then the label or excess label can be removed by suitable methods, such as separation, washing, etc. The sample, possibly containing an item of interest associated with a label, is passed to the optical flow cell on the structure and the label is detected by optics associated with the flow cell thereby indicating presence of the item of interest.  
     [0204] An exemplary construction of an electrical circuit  82  which may be used with the structures described herein is shown schematically in FIG. 34. A first induced electrical pulse or voltage, provided at a determined magnitude and frequency by the circuit  82 , can be used to reduce a likelihood of contamination of elements of the structures. Additionally, a second induced electrical pulse or voltage can be used to lyse cells, or provide other desirable effects, such as releasing an item of interest from a binding member.  
     [0205] As shown in the embodiment illustrated in FIG. 34, an electrical power source  84  of about 120 VAC RMS at a frequency substantially within the range of about 50 to about 60 Hertz is connected to a primary-side winding of a fused, isolation transformer  85  which provides electrical isolation from power source  84  via mutual magnetic coupling. A secondary-side winding of transformer  85  translates the primary-side power source  84  in a 1:1 ratio.  
     [0206] The secondary-side 120VAC RMS is subsequently converted to a DC voltage via connection to a full-wave bridge rectifier and filter capacitor  86 . The output of the rectifier and filter capacitor  86  is transferred through an adjustable high voltage regulator circuit  87  to produce a highly filtered and regulated positive 1.25 VDC to 100 VDC output. The output of the regulator  87  is then connected to a non-inductive current limiting resistor  88  of sufficient resistance and wattage to reduce current flow to a predetermined current level.  
     [0207] The output of resistor  88  is then connected to one Normally Open terminal of a circuit  89  comprising a Double Pole/Double Throw (DPDT) relay and transistor-based coil control. The other Normally Open terminal of circuit  89  is connected to a negative side of regulator circuit  87  via connection to a collector of a high voltage semiconductor rapid switching device which, in one embodiment, may be an insulated gate bipolar transistor or IGBT  90 . IGBT  90  provides for rapid pulsing of the high voltage output with pulse widths narrower than can be obtained through electromechanical means.  
     [0208] An emitter of IGBT  90  is connected to a negative side of the regulator circuit  87 . A controlling insulated gate of the IGBT  90  is connected to a signal control element  91  which may be a microcontroller. A transistorized coil control input is also connected to the IGBT  90  for controlling energizing of the relay coil. The two Normally Closed terminals of circuit  89  are unconnected to anything. The two common poles of circuit  89  are then connected to another DPDT relay with a transistorized coil control  92 . In this manner, circuit  89  establishes a high voltage electrical connection to control  92 .  
     [0209] A first pole of circuit  89  is connected to a Normally Open and a Normally Closed terminal of control  92 . A second pole of circuit  89  is connected to the other remaining Normally Open and Normally Closed terminals of control  92 . The transistorized coil control  92  input is connected to control element  91 . Two output poles of control  92  are subsequently connected, via high voltage insulating wires  94 A and  94 B to two conductors or electrodes  93 A and  93 B, respectively. In this manner, control  92  can reverse electrode  93 A and  93 B polarity as needed to control generation of aqueous electrical species present in fluid  95  into which the electrodes  93 A and  93 B are inserted or adjacent to which the electrodes  93 A and  93 B are disposed or located.  
     [0210] Electrodes  93 A and  93 B may be composed of any suitable material, such as chemically inert alloys, platinum and the like. The electrodes  93 A and  93 B may have any appropriate geometry such that asymmetrical voltage gradients in the fluid  95  are reduced. It is to be noted that at least one of the electrodes  93 A and  93 B may be a pipettor associated with one of the structures described herein. Also, a container, such as container  1  or  15 , may be made from an electrically conductive material such that when that container  1  or  15  is located proximately at least one of the electrodes  93 A and  93 B, that container  1  or  15  may become a conductive portion of the circuit  82 .  
     [0211] It is to be noted that physical contact among the electrodes  93 A and  93 B and the fluid  95  is not necessary in all embodiments or utilizations of the circuit  82 . Physical contact of the electrodes  93 A and  93 B with the fluid  95 , such as a buffer, sample or the like, permits current to flow in the fluid  95  as a result of a voltaic potential between the two electrodes  93 A and  93 B. The current flowing in the fluid  95  produces a voltage drop in the fluid  95 . This voltage drop produces the desired effects. If a relatively increased voltage, such as greater than or equal to about 1 KV, were present between the electrodes  93 A and  93 B, then it may not be necessary to have physical contact among the electrodes  93 A and  93 B and the fluid  95 .  
     [0212] With the above apparatus in place, parameters may be optimized to provide desired molecular behavior, which may include lysis, elution and/or fragmentation of DNA/RNA, in the fluid  95 . As an example, the parameters may include a voltage (V1) substantially within the range of about 2 to about 100 volts DC, a voltage pulse period (Tp) substantially within the range of about 0.5 to about 1000 milliseconds, a High Voltage Pulse Minimum Duty Cycle (Tmin) of about 5%, a High Voltage Pulse Maximum Duty Cycle (Tmax) of about 95%, and a Pulse Train Duration (Td) substantially within the range of about 1 to about 300 seconds.  
     [0213] Use of the circuit  82  illustrated in FIG. 34 with the parameters specified above may provide for reduction of liquid and solid waste as well as improved reduction of the likelihood of contamination. In one example, the electrodes  93 A and  93 B are disposed in contact with or sufficiently adjacent to the fluid  95 . A voltaic signal, such as a variable width pulsed DC voltage signal and the like, is applied between the electrodes  93 A and  93 B with sufficient voltage application time to elicit desired performance. It is believed that that signal may elute or lyse a nucleic acid. Alternatively, that signal may attenuate, change or otherwise effect biological and/or bio-molecular elements, such as a nucleic acid and the like, in the fluid  95  such that those elements have a reduced ability to be amplified or detected in a PCR reaction.  
     [0214] In another embodiment, the signal applied to the electrodes  93 A and  93 B may be sufficient to lyse cells in a sample.  
     [0215] In a further embodiment, the signal applied to the electrodes  93 A and  93 B may be sufficient to remove at least one nucleic acid from a binding member present in a container containing the sample. For example, the binding member may be specific to at least one nucleic acid and may be provided on a particle mixed with the sample or on the container itself. The at least one nucleic acid may bind with the binding member. Upon application of the signal to the electrodes  93 A and  93 B, the at least one nucleic acid is removed from the binding member.  
     [0216] In another embodiment, the signal applied to the electrodes  93 A and  93 B may be sufficient to cause disassociation, denaturing or unzipping of the at least one nucleic acid.  
     [0217] If one of the electrodes  93 A or  93 B were a pipettor  12  or  19 , then a likelihood of contamination of that pipettor  12  or  19  may be reduced independent of washing of that pipettor  12  or  19 . For example, one of the electrodes  93 A or  93 B could be operatively connected with a washer  23  that may include a buffer fluid reservoir for washing a pipettor  12  and/or  19 . That electrode  93 A or  93 B can provide an electrical current to the reservoir. The electrical current is carried through the buffer solution in the reservoir to the conductive pipettor  12  and/or  19 , i.e. the pipettor  12  or  19  acts as the other electrode  93 A or  93 B, thereby reducing the likelihood of contamination of the pipettor  12  and/or  19 .  
     [0218] Alternatively, one electrode  93 A or  93 B could be mounted to a transport mechanism which moves the pipettor  12  or  19  and may be activated when moved to a washing reservoir or conductive plate to reduce the likelihood of contamination of the associated pipettor  12  and/or  19 .  
     [0219] In some embodiments, the electrodes  93 A and  93 B may avoid sample contact by being selectively electrically coupled to a conductive container, such as container  1  or  15 , and an electrical current may be applied to the electrodes  93 A and  93 B to induce an electrical state in the sample in the container  1  or  15  for lysis or elution or reduction of sample or synthesized sample signal.  
     [0220] Further, after a PCR or other appropriate reaction has taken place and the item of interest has been detected such that the detection of the item of interest is complete, the contents of the associated container may be exposed to the electrodes  93 A and  93 B such that the item of interest in the container has reduced activity or reduced detectability.