Dual vapor chamber for thermocyclers

Abstract

Systems including thermocyclers with dual vapor champers and methods of use of the same are described. The system can be used in performing automated Polymerase Chain Reaction (PCR). The system can include a thermocycler that can thermocycle samples in a PCR cartridge. The thermocycler can include a thermal element, and a first vapor chamber thermally coupled to the thermal element. The first vapor chamber can thermally couple to the PCR cartridge during thermocycling of the PCR cartridge. The system can include an imager and a processor communicatively coupled with each of the thermocycler and the imager. The processor can control the operation of each of the thermocycler and the imager to perform digital PCR. The processor can thermocycle the sample in the PCR cartridge with the thermocycler, and image the sample in the PCR cartridge with the imager.

Description

[0001] DUAL VAPOR CHAMBER FOR THERMOCYCLERS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Application No. 63 / 529,315, filed on July 27, 2023, and entitled “DUAL VAPOR CHAMBER FOR THERMOCYCLERS”, the entirety of which is hereby incorporated by reference herein.

[0004] BACKGROUND

[0005] Polymerase chain reaction (PCR) is widely used to rapidly make large numbers of copies of a specific DNA sample. Through PCR, a very small sample of DNA can be amplified to a large enough amount to study in detail.

[0006] Droplet digital PCR (ddPCR) divides PCR samples into partitions (e.g., water-in-oil droplets). See, e.g., Hindson et al., 2011, Anal.Chem. 83:8604-8610; Pinheiro et al., 2012, Anal. Chem. 84: 1003-1011. The droplets support PCR amplification of template molecules, if present, and use reagents that are capable of specifically generating a signal from target amplicons, i.e.. amplicons from the target sequences. Following PCR, signal from each droplet is read to determine the number of positive droplets for each target amplified in the original sample (for example, including partitions having multiple different targets as well as portions only having single or no target signal). Digital PCR is a refinement of conventional PCR and can be more precise than conventional PCR. However, operator errors can reduce precision in digital PCR.

[0007] BRIEF SUMMARY

[0008] One aspect of the present disclosure relates to a method of performing automated digital Polymerase Chain Reaction (PCR). The method can include receiving a sample in a PCR cartridge, thermocycling the sample in the PCR cartridge with a thermocycler of an automated PCR system, and imaging the sample in the PCR cartridge with an imager of the automated PCR system. The thermocy cler can include a thermal element and a first vapor chamber thermally coupled to the thermal element and that can thermally couple to the PCR cartridge to thermocycle the sample. In some embodiments, the first vapor chamber can include an envelope having interior surfaces defining an interior volume, a wick extending around at least a portion of the interior volume, and working liquid contained within the interior volume. In some embodiments, the first vapor chamber can include a top and an opposing bottom. In some embodiments, the interior surfaces can include an evaporation surface at the top and a condensing surface at the bottom. In some embodiments, a first portion of the wick extends across the evaporation surface and a second portion of the wick extends across the condensing surface. In some embodiments, the wick can collect condensed liquid from the condensing surface and transport the condensed liquid to the evaporation surface.

[0009] In some embodiments, the first vapor chamber includes a top and an opposing bottom. In some embodiments, the interior surfaces include a first surface at the top and a second surface at the bottom. In some embodiments, a first portion of the wick extends across the first surface and a second portion of the wick extends across the second surface. In some embodiments, the wick can collect condensed liquid from one of the first surface, or the second surface. In some embodiments, the wick can transport the collected condensed liquid to the other one of the first surface, or the second surface. In some embodiments, the wick can be a mesh wick.

[0010] In some embodiments, the first surface and the second surface are connected via at least one column. In some embodiments, the at least one column can be a copper column. In some embodiments, the first vapor chamber has a first orientation with the top of the first vapor chamber coupling to the thermal element.

[0011] In some embodiments, the thermocycler further includes a second vapor chamber having a second top and an opposing second bottom. In some embodiments, the second vapor chamber has a second orientation opposite to the first orientation of the first vapor chamber. In some embodiments, the second top of the second vapor chamber is coupled to the thermal element such that the thermal element is located between the top of the first vapor chamber and the second top of the second vapor chamber.

[0012] In some embodiments, the thermocycler further includes heat exchanger fins coupled to the second bottom of the second vapor chamber, and a fan that can blow air across the heat exchanger fins. In some embodiments, the heat exchanger fins can have a fin bottom coupled to the second bottom of the second vapor chamber. In some embodiments, the fins extend in a first direction perpendicularly away from the second bottom of the second vapor chamber. In some embodiments, the fan is adjacent to a fin top of the heat exchanger fins. In some embodiments, the fan is oriented to blow air from the fin top towards the fin bottom of the heat exchanger fins.

[0013] One aspect of the present disclosure relates to a system for performing automated Polymerase Chain Reaction (PCR). The system includes a thermocycler that can thermocycle samples in a PCR cartridge. The thermocycler includes a thermal element, and a first vapor chamber thermally coupled to the thermal element and that can thermally couple to the PCR cartridge during thermocycling of the PCR cartridge. The system includes an imager, and a processor communicatively coupled with each of the thermocycler and the imager. In some embodiments, the processor can control the operation of each of the thermocycler and the imager to perform digital PCR. In some embodiments, the processor can thermocycle the sample in the PCR cartridge with the thermocycler, and image the sample in the PCR cartridge with the imager.

[0014] In some embodiments, the first vapor chamber includes an envelope having interior surfaces defining an interior volume, a wick extending around at least a portion of the interior volume, and working liquid contained within the interior volume. In some embodiments, the first vapor chamber can have a top and an opposing bottom. In some embodiments, the interior surfaces include an evaporation surface at the top and a condensing surface at the bottom. In some embodiments, a first portion of the wick extends across the evaporation surface and a second portion of the wick extends across the condensing surface. In some embodiments, the wick can collect condensed liquid from the condensing surface and transport the condensed liquid to the evaporation surface.

[0015] In some embodiments, the first vapor chamber can include a top and an opposing bottom. In some embodiments, the interior surfaces can include a first surface at the top and a second surface at the bottom. In some embodiments, a first portion of the wick extends across the first surface and a second portion of the wick extends across the second surface.

[0016] In some embodiments, the wick can collect condensed liquid from one of the first surface, or the second surface. In some embodiments, the wick can transport the collected condensed liquid to the other one of the first surface, or the second surface. In some embodiments, the wick can be a mesh wick. In some embodiments, the first surface and the second surface are connected via at least one column. In some embodiments, the at least one column can include a copper column. In some embodiments, the first vapor chamber has a first orientation with the top of the first vapor chamber coupling to the thermal element.

[0017] In some embodiments, the thermocycler further includes a second vapor chamber having a second top and an opposing second bottom. In some embodiments, the second vapor chamber has a second orientation opposite to the first orientation of the first vapor chamber. In some embodiments, the second top of the second vapor chamber is coupled to the thermal element such that the thermal element is located between the top of the first vapor chamber and the second top of the second vapor chamber.

[0018] In some embodiments, the thermocycler further includes heat exchanger fins coupled to the second bottom of the second vapor chamber, and a fan that can blow air across the heat exchanger fins. In some embodiments, the heat exchanger fins have a fin bottom coupled to the second bottom of the second vapor chamber. In some embodiments, the fins extend in a first direction perpendicularly away from the second bottom of the second vapor chamber. In some embodiments, the fan is adjacent to a fin top of the heat exchanger fins. In some embodiments, the fan is oriented to blow air from the fin top towards the fin bottom of the heat exchanger fins. In some embodiments, the heat exchanger fins can be an array of planar members. In some embodiments, each of the planar members can be a fin of the heat exchanger fins. In some embodiments, the planar members in the array of planar members are parallel.

[0019] Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating various embodiments, are intended for purposes of illustration only and are not intended to necessarily limit the scope of the disclosure.

[0020] BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a perspective view of one embodiment of a system for digital PCR.

[0022] Figure 2 is a perspective view of one embodiment of the system with a door in the second, open position.

[0023] Figure 3 is a section view taken along cutting plane A-A and showing a first layout of the deck.

[0024] Figure 4 depicts a second layout of the deck. Figure 5 depicts a third layout of the deck.

[0025] Figure 6 is a schematic depiction of exemplary consumables.

[0026] Figure 7 is a perspective view of one embodiment of a sample tube system.

[0027] Figure 8 is a top view of one embodiment of the reagent cartridge.

[0028] Figure 9 is a perspective view of one embodiment of a pipette tip box.

[0029] Figure 10 is a perspective view of one embodiment of a PCR chip that is a micro well cartridge and the PCR chip lid.

[0030] Figure 11 is a perspective view of another embodiment of the PCR chip that is a droplet cartridge.

[0031] Figure 12 is a perspective view of one embodiment of an RNA strip.

[0032] Figure 13 is a schematic depiction of control of one embodiment of the system.

[0033] Figure 14 is a depiction of one embodiment of a thermocycler.

[0034] Figure 15 is a perspective view of another embodiment of a thermocycler.

[0035] Figure 16 is a depiction of another embodiment of a thermocycler.

[0036] Figure 17 is a depiction of one embodiment of a vapor chamber.

[0037] Figure 18 is a top view of one embodiment of a first vapor chamber.

[0038] Figure 19 is a perspective view of one embodiment of a second vapor chamber.

[0039] Figure 20 is a perspective view of another embodiment of the thermocycler.

[0040] Figure 21 is perspective view of another embodiment of a thermocycler.

[0041] Figure 22 is a graphical depiction of results of embodiments of a thermocycler including at least one vapor chamber.

[0042] Figure 23 is a flowchart illustrating one embodiment of a process for automated PCR.

[0043] DETAILED DESCRIPTION

[0044] Digital PCR (dPCR) is a method for analyzing nucleic acid molecules. dPCR is a quantitation method in which target molecules in samples are partitioned into many separate reactions, and digital analyses are performed for characterization of the target molecules. As used herein, each of these separate reactions is described as a partition. As of be discussed in greater length below each of these partitions can be formed on the PCR chip including, for example, in a micro well or as a discrete droplet on the PCR chip. Because of the partitioning, the vast majority7of reactions contain either one or zero target molecules, which can be detected using different modalities. Digital PCR is advantageous in that it avoids any need to interpret the time dependence of fluorescence intensity — an analog signal — along with the potential underlying uncertainty of non-exponential amplification during early cycles.

[0045] Current platforms and methods for performing digital PCR and / or related analyses, however, can be subject to limitations, including: complex setups, low dynamic range, large amounts of operator burden, low precision accounting from low number of partitions, lack of automation, lack of integration with sample extraction or purification, low sample utilization (% of nucleic acid present in the final reaction compared to input), risk of operator error, throughput, multiplexing ability7, slow turn-around times, and other limitations.

[0046] While dPCR has significant benefits, in some implementations it can have significant challenges. These challenges, in many instances, are intimately tied to the benefits of digital PCR. For example, as digital PCR is more sensitive than traditional PCR. samples containing smaller amounts of the target, such as a target nucleic acid including, for example, cell-free DNA, can be analyzed using digital PCR. However, these lower concentrations of the target increase risks associated with contamination and also increase challenges associated with concentration of the target and / or replication of the same.

[0047] Disclosed herein are embodiments of systems, devices, and methods that provide automated PCR, and specifically that provide automated digital PCR. This automated digital PCR method can include sample preparation steps such as lysing the sample, concentrating target with, for example, magnetic beads and / or the creation of one or several assay mixes. The automated digital PCR method can further include transfer of prepared sample to a PCR chip, amplification of the target in the PCR chip via thermal cycling, the imaging of the PCR chip, and / or the analyzing of the image of the PCR chip to detect the presence or absence of the target.

[0048] These embodiments include features and / or components to decrease and / or limit contamination. For example, the system may include a pipettor that can include a drip tray. The drip tray can be deployed to prevent substance from falling from the pipettor and contaminating a sample. Further features and / or components that can facilitate in decreasing and / or limiting contamination include a graphical user interface ("GUI") that facilitates in the set up and / or running of an assay. The GUI can guide the user through the loading of consumables and / or sample into the system so as to decrease the risk of contamination. Further features and / or components that can facilitate in decreasing and / or limiting contamination include the deck layout, internal air flow management in addition to providing caps for sample tubes, when possible. The deck layout allows the pipettor to move in a way that limits or prevents substance from falling from the pipettor and contaminating a sample. Modules that generate amplicons such as pre-amplification modules are located at the back of the instrument while the air flow inside the instrument may be from front to back such that contaminant if comes about may be pushed out away from other preparation modules. Also sample tubes may contain a pierceable membrane or cap to prevent any target molecules from escaping through air.

[0049] The embodiments disclosed herein can further include features to improve efficacy of an assay for samples with low concentration of target and / or to decrease the amount of time required to successfully complete an assay. Such features can include, for example, the preconcentration of target in a pipette tip. Through this preconcentration, the efficacy of substrate concentration with a magnetic separator can be improved, thereby decreasing time to successfully complete an assay and / or improving assay efficacy for samples with low concentration of target. In some embodiments, an additional feature that decreases the amount of time to complete an assay includes altering materials of one or several consumables to increase heat conduction. For example, one or several of the consumables can include plastic doped with a heat conductive material, such as metal, to improve heat conduction of that consumable. These doped consumables can have improved heat conductivity which can decrease the amount of time required to change the temperature of these consumables and / or to change the temperature of the contents of these consumables.

[0050] Some embodiments disclosed herein are directed at improving imaging. For example, some embodiments relate to a process of image normalization. This process can utilize an artificial intelligence classifier, which can be a machine learning model to identify image pixels belonging to a partitioned and image pixels belonging to the background. The process can further evaluate one or several partitioned pixels and generate a normalization value, which can then be applied to pixel values to create normalized pixel values. These normalized pixel values can increase and / or improve image analysis, and can thereby improve accuracy of digital PCR, by mitigating the impact of illumination variation across a PCR chip.

[0051] Some embodiments disclosed herein are directed at automatically confirming the proper generation of partitions of sample in a PCR chip. This can include a process for determining whether some or all of the partitions are monolayer partitions. The process can determine whether some or all the partitions are monolayer partitions via artificial intelligence, and specifically via a machine learning model. Image analysis can then be performed on monolayer partitions, thereby preventing the skewing of assay results by one or several nonmonolayer partitions.

[0052] Taken together or in sub-combinations thereof, these different features and embodiments enable the creation of a completely automated system for performing digital PCR. This automated system for performing digital PCR. because of these different features and embodiments is able to accurately and quickly perform assays on samples, including samples with a small amount of target.

[0053] With reference now to Figure 1, a perspective view of one embodiment of a system 100 for automated digital PCR is shown. The system 100 can be configured to perform automated sample extraction and digital PCR. The system 100 can be used for any application of digital PCR including, for example, Non-invasive Prenatal Testing (“NIPT”), Fetal Fraction (“FF”), oncology screening, genetic screening, carrier screening, quantification including disease state quantification and / or transplant panels, and / or syndrome panels. In some embodiments, the system can be used for digital PCR with, for example, cell free DNA (“cfDNA”), RNA, cDNA, microRNA. mRNA, mitochondrial DNA, exosomic nucleic acid and / or genomic DNA.

[0054] In some embodiments, the system 100 can receive sample, which can be plasma, and in some embodiments, can be 4 mL of plasma. DNA extraction can be performed on the sample, which DNA extraction can be a cfDNA extraction. After cfDNA extraction has been performed, the workflow protocol performed by the system 100 can vary based on the assay that is being performed. For example, if a cfDNA (e g., NIPT or cancer or transplantation monitoring assay) is being performed, the system 100 can perform DNA quantitation, preamplification, cfDNA (e.g., NIPT assay preparation, which can comprise fetal fraction) digital partitioning, thermocycling, and imaging. Results can be generated by analyzing images generated during imaging. The system 100 can include a housing 102 that can have a top 104, a bottom 106, a front 108, a back 110. a first side 112, and a second side 114. The housing 102 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the housing 102 can be made of one or several plastic components, metal components, and / or composite components.

[0055] The housing 102 can define an internal volume in which one or several assays can be performed. This internal volume can, in some embodiments, be accessible by a door 116 which can be moved from a first position to a second position. In some embodiments, the door 116 can enclose the internal volume when the door 116 is in the first position, and the internal volume can be accessible when the door 116 is in the second position. In the embodiment of the system 100 depicted in Figure 1, the door 116. which is in the first, closed position, is movably connected to the housing 102 via one or several hinges 118.

[0056] With reference now to Figure 2, a perspective view of one embodiment of the system 100 with the door 116 in the second, open position is shown, opening the internal volume 120 of the system. As seen in Figure 3, a section view' taken along cutting plane A-A and showing the internal volume 120 of the system 100. the internal volume 120 defined by the housing 102 can be divided into a sample prep module 122 and a reader module 124.

[0057] The sample prep module 122 can provide a space for completing sample preparation tasks. The sample prep module 122 can include, for example, a deck 126 comprising a plurality of positions 128, each position 128 configured to receive a consumable. In some embodiments, the deck 126 can be removable and / or replaceable. In some embodiments, the deck 126 can be removed and / or replaced to maintain the cleanliness of the deck and / or to prevent contamination.

[0058] The consumables receivable in the positions 128 of the deck 126 can include, for example, one or several sample tubes, one or several sample tube racks, one or several reagent cartridges, one or several tip boxes, one or several DNA quantification strips, one or several assay strips, one or several PCR cartridges, one or several PCR cartridge leads, one or several magnetic separation plates, one or several transfer plates, or the like. In the embodiment shown in Figure 3, each position 128 has received its consumable.

[0059] In some embodiments, a position 128 can be passive in that it merely receives a consumable, and in some embodiments, a position 128 can be active in that it can perform one or several operations on the consumable and / or have an effect on the consumable. Exemplary active positions 128 can include, for example, a pre-amplification thermocycler 130 (also referred to herein as a "pre-amp thermocycler 130”), a heater / shaker 132. a magnetic separator 134, a chiller 136, and an RNA heater 138.

[0060] In some embodiments, the pre-amp thermocycler 130 can be configured to altematingly heat and cool samples in a consumable on the pre-amp thermocycler 130. The pre-amp thermocycler 130 can be configured to increase the concentration of a target before the amplification step and / or before thermocycling as performed by and / or in the reader module 124. In some embodiments, the pre-amp thermocycler 130 can be of particular utility in embodiments in which the sample has a low concentration of target.

[0061] The heater / shaker 132 can receive the lysis binding plate that can include a plurality of wells, and the heater / shaker 132 can heat and shake samples in the lysis binding plate. The lysis binding plate can, in some embodiments, comprise a plastic doped with metal to increase the thermal conductivity of the lysis binding plate. In some embodiments, the heating and the shaking of the lysis binding plate while on the heater / shaker 132 can facilitate lysis of sample contained within the lysis binding plate as well as binding of target molecules to affinity7magnetic beads.

[0062] The magnetic separator 134 can receive a magnetic separation plate that can include a plurality of wells. The magnetic separator 134 can separate target from other liquid in the wells when the target is bound to magnetic beads. Specifically, upon placing sample with target bound to magnetic beads in the magnetic separation plate and on the magnetic separator 134, a magnetic field can be created through the plurality of wells of the magnetic separation plate, which magnetic field can attract the magnetic beads. With the magnetic beads held in place, and in some embodiments against a side and / or w ell of one or several w ells by the magnetic field, the supernatant can be aspirated from the one or several wells, thereby separating the target from the supernatant. This separation can be further improved by one or several wash steps.

[0063] The chiller 136 can facilitate in cooling sample and / or reagents that need to be kept cold while it is waiting to be processed or removed from the instrument.

[0064] The RNA heater 138 can be used to heat up samples that may require different heating protocol than that provided by the Lysis-heater if used at the same time. The reader module 124 can include a thermocycler and an imager that can be contained within a reader module housing 140. A PCR chip 142 can be loaded with sample in the sample prep module 122 and the PCR chip 142 can then be placed in a chip tray 144. The chip tray 144 can be driven by a motor, which can be controlled to move the chip tray 144 into or out of the reader module 124. Via the chip tray 144, PCR chips 142 can be moved into the reader module for thermocycling and / or imaging.

[0065] The internal volume 120 can further include a pipettor 150. The pipettor 150 can be a multichannel pipettor 150 and can include, for example, two channels, three channels, four channels, five channels, six channels, seven channels, eight channels, nine channels, ten channels, 15 channels, 20 channels, or any other or intermediate number of channels. The pipettor 150 can be controlled to move above and across the deck 126 in, for example, in the x-axis, or in an x-direction. as indicated by arrow 152. and / or in the y-axis, or in a y- direction, as indicated by arrow 154.

[0066] In some embodiments, the pipettor 150 is movably coupled to a gantry 156, which gantry 156 is movably coupled to the housing 102 via tracks 158. These tracks 158 include a first track coupled to a first side 112 of the housing 102 and the second track coupled to a second side 114 of the housing 102. In some embodiments, the pipettor 150 is movable in the x-direction via movement of the gantry 156 along the tracks 158. In some embodiments, this movement of the gantry 156 along the tracks 158 can be caused and / or controlled by an x-axis motor. In some embodiments, the pipettor 150 is movable in the y-direction via movement of the pipettor 150 along the gantry 156. In some embodiments, this movement of the pipettor 150 along the gantry 156 can be caused and / or controlled by ay-axis motor.

[0067] Via the combination of the tracks 158 and the gantry 156, the pipettor 150 can be moved to a location above each position 128 on the deck 126 for receiving a consumable, and thus can access the consumables and / or contents of the consumables at each of those positions 128. In some embodiments, the pipettor 150 can thus be used to aspirate substances from and / or dispense substances to one or several wells, PCR chips, or sample tubes at each position 128.

[0068] The deck 126 can include different layouts, and specifically can have different arrangement of positions 128 for receiving consumables. With reference now to Figure 4, a second layout of the deck 126 is shown. As seen, the deck 126 can include, in similar layout to the embodiment of Figure 3, the pre-amp thermocycler 130 which can hold one or several preamplification strips, a heater / shaker 132 which is depicted as holding a lysis-binding well plate, a magnetic separator 134 which is depicted as holding a magnetic separation plate, a chiller 136, and an RNA heater 138.

[0069] As seen in Figure 4, the deck 126 further includes one or several sample tube holders 150 configured to receive and hold one or several sample tubes specifically, the embodiment of the deck 126 show n in Figure 4 includes four sample tube holders 151, each of which can hold a plurality of sample tubes, and specifically can each hold eight sample tubes.

[0070] The deck 126 further includes one or several reagent cartridge holders 152. In the embodiment shown in Figure 4, the deck 126 includes four reagent cartridge holders 152, each of w hich can hold a reagent cartridge. In some embodiments, each of the reagent cartridges can comprise a plurality of w ells which can contain one or several substances such as one or several reagents for performing an assay.

[0071] The deck 126 includes one or several tip box holders 154. In the embodiment shown in Figure 4, the deck 126 includes four tip box holders 154, each of which can hold a tip box. Each tip box can comprise a plurality of compartments, each of which is sized and shaped to hold a pipette tip. In some embodiments, and during operation of the system, the pipettor 150 can move to one of the tip box holders 154 and retrieve one or several pipette tips from the tip box at the tip box holder 154. These pipette tips can then be used by the pipettor 150 for one or several pipetting operations including, for example, aspirating and / or dispensing one or several substances. Upon completion of use of a pipette tip, the pipettor 150 can return that used pipette tip to a compartment in the tip box. In some embodiments the compartment to which the used pipette tip is returned is the same compartment from which the pipette tip was taken.

[0072] The deck 126 includes one or several quantification strip holders 156. In the embodiment shown in Figure 4, the deck 126 includes four quantification strip holders 156. In some embodiments, each of the quantification strip holders 156 can hold a quantification strip. The quantification strip can comprise a plurality of wells for use in DNA quantification.

[0073] The deck 126 includes one or several assay strip holders 158. In the embodiment shown in Figure 4, the deck 126 includes four assay strip holders 158. In some embodiments, each of the assay strip holders 158 can hold an assay strip. The assay strip can comprise a plurality of wells for use in performing one or several assay and / or in preparing sample for one or several assays. The deck 126 includes one or several PCR cartridge holders 160 and / or one or several PCR cartridge lid holder 162. In some embodiments, a PCR cartridge holder 160 can hold the stack of PCR cartridges and the PCR cartridge lid holder 162 can hold one or several PCR cartridge lids.

[0074] In some embodiments, the layout of the deck 126 can improve efficiency of performing one or several assays with the system 100 and / or can decrease risk of contamination between samples and / or assays. In some embodiments, this contamination can come, for example, as a result of air-suspended substances such as DNA, dripping of substances such as DNA, consumable engagement difficulty, gantry precision, or the like. This contamination can originate from, for example, a pre-amp thermocycler, a reader module, or from a sample.

[0075] In some embodiments, the deck layout can mitigate contamination. For example, positions on the deck 128 can be spaced to allow accessibility to the consumables in each position.

[0076] Further, extra space can be provided around consumables and / or positions that are likely sources of contamination. This spacing can mitigate risks of contamination from airsuspended substances.

[0077] In some embodiments, for example positions 128 on the deck 126 can be laid out so that an assay can be performed for sample by largely moving the pipettor 150 solely in the y-axis. Thus, as seen in the embodiment of Figure 4, the sample tubes, the reagent cartridges, the tip boxes, and the DNA quant strips are roughly arranged to form a line extending in the y- direction. Thus, while performing an assay on a sample, if there is any drip, that drip will fall in a well associated with that sample.

[0078] In some embodiments, positions 128 can be located to ease consumable engagement. For example, the pre-amp thermocycler 130 can be elevated above the deck. To prevent contamination arising from a user reaching over the pre-amp thermocycler 130, the pre-amp thermocycler 130 is located adjacent to the back 110 of the housing 102. Further, the heater / shaker 132, the magnetic separator 134. and the chiller 136 are arranged with the easiest to engage with the consumables being located relatively most proximate to the back 110 of the housing 102, and the hardest to engage being located relatively most proximate to the front 108 of the housing 102. For example, in Figure 4, located relatively most proximate to the back 110 of the housing 102 is the heater / shaker 132, then the magnetic separator 134, and then the chiller 136. The pipetor 150 is provided with a home location proximate to the intersection of the back 110 and the second side 114. The movement of the pipetor 150 is more precise as the pipetor 150 moves closer to this home location. Accordingly, and as the pipete tips have the tightest tolerance, the pipete tips in the tip boxes 154 are located closest to that home position of the pipettor 150.

[0079] With reference now to Figure 5, a third layout of the deck 126 is shown. The third layout can be configured for digital droplet PCR (DDPCR). As seen, the deck 126 can include, in similar layout to the embodiments of Figures 3 and 4, the pre-amp thermocycler 130 which can hold one or several pre-amplification strips, a heater / shaker 132 which is depicted as holding a lysis-binding well plate, a magnetic separator 134 which is depicted as holding a magnetic separation plate, a chiller 136, and an RNA heater 138.

[0080] As seen in Figure 5, the deck 126 further includes one or several sample tube holders 150 configured to receive and hold one or several sample tubes specifically, the embodiment of the deck 126 shown in Figure 5 includes four sample tube holders 151, each of w hich can hold a plurality of sample tubes, and specifically can each hold eight sample tubes.

[0081] The deck 126 further includes one or several reagent cartridge holders 152. In the embodiment shown in Figure 5, the deck 126 includes four reagent cartridge holders 152, each of which can hold a reagent cartridge. In some embodiments, each of the reagent cartridges can comprise a plurality of wells which can contain one or several substances such as one or several reagents for performing an assay.

[0082] The deck 126 includes one or several tip box holders 154. In the embodiment shown in Figure 5, the deck 126 includes four tip box holders 154, each of which can hold a tip box. Each tip box can comprise a plurality of compartments, each of which is sized and shaped to hold a pipete tip. In some embodiments, and during operation of the system, the pipetor 150 can move to one of the tip box holders 154 and retrieve one or several pipette tips from the tip box at the tip box holder 154. These pipete tips can then be used by the pipetor 150 for one or several pipeting operations including, for example, aspirating and / or dispensing one or several substances. Upon completion of use of a pipete tip, the pipettor 150 can return that used pipete tip to a compartment in the tip box. In some embodiments the compartment to which the used pipete tip is returned is the same compartment from which the pipete tip w as taken. The deck 126 includes one or several quantification strip holders 156. In the embodiment shown in Figure 5, the deck 126 includes four quantification strip holders 156. In some embodiments, each of the quantification strip holders 156 can hold a quantification strip. The quantification strip can comprise a plurality of wells for use in DNA quantification.

[0083] The deck 126 includes one or several assay strip holders 158. In the embodiment shown in Figure 5, the deck 126 includes four assay strip holders 158. In some embodiments, each of the assay strip holders 158 can hold an assay strip. The assay strip can comprise a plurality of wells for use in performing one or several assay and / or in preparing sample for one or several assays.

[0084] The deck 126 includes one or several PCR cartridge holders 160 and / or one or several PCR cartridge lid holder 162. In some embodiments, a PCR cartridge holder 160 can hold the stack of PCR cartridges and the PCR cartridge lid holder 162 can hold one or several PCR cartridge lids.

[0085] The deck 126 can include one or several droplet generators 164. The one or several droplet generators 164 can comprise one or several droplet generator chips, and can be configured to generate droplets for use in the DDPCR. In some embodiments, the one or several droplet generators 164 can include one or several droplet generating chips such as, for example, DG8TM cartridge sold by Bio-Rad Laboratories, Inc.

[0086] In some embodiments, the layout of the deck 126 can improve efficiency of performing one or several assays with the system 100 and / or can decrease risk of contamination between samples and / or assays. In some embodiments, this contamination can come, for example, as a result of air-suspended substances such as DNA. dripping of substances such as DNA, consumable engagement difficulty, gantry precision, or the like. This contamination can originate from, for example, a pre-amp thermocycler, a reader module, or from a sample.

[0087] In some embodiments, the deck layout can mitigate contamination. For example, positions on the deck 128 can be spaced to allow accessibility to the consumables in each position.

[0088] Further, extra space can be provided around consumables and / or positions that are likely sources of contamination. This spacing can mitigate risks of contamination from airsuspended substances.

[0089] In some embodiments, for example positions 128 on the deck 126 can be laid out so that an assay can be performed for sample by largely moving the pipettor 150 solely in the y-axis. Thus, as seen in the embodiment of Figure 5, the sample tubes, the reagent cartridges, the tip boxes, and the DNA quant strips are roughly arranged to form a line extending in the y- direction. Thus, while performing an assay on a sample, if there is any drip, that drip will fall in a well associated with that sample.

[0090] In some embodiments, positions 128 can be located to ease consumable engagement. For example, the pre-amp thermocycler 130 can be elevated above the deck. To prevent contamination arising from a user reaching over the pre-amp thermocycler 130. the pre-amp thermocycler 130 is located adjacent to the back 1 10 of the housing 102. Further, the heater / shaker 132, the magnetic separator 134, and the chiller 136 are arranged with the easiest to engage with the consumables being located relatively most proximate to the back 110 of the housing 102, and the hardest to engage being located relatively most proximate to the front 108 of the housing 102. For example, in Figure 5, located relatively most proximate to the back 110 of the housing 102 is the heater / shaker 132, then the magnetic separator 134, and then the chiller 136.

[0091] The pipettor 150 is provided with a home location proximate to the intersection of the back 110 and the second side 114. The movement of the pipettor 150 is more precise as the pipettor 150 moves closer to this home location. Accordingly, and as the pipette tips have the tightest tolerance, the pipette tips in the tip boxes 154 are located closest to that home position of the pipettor 150.

[0092] With respect to Figure 6, a schematic depiction of exemplar}7consumables 200 is shown. The consumables 200 can be received within positions within the deck 126 of the system 100 and can be used in performing an assay. In some embodiments, some or all of the consumables 200 can include one or several wells, which wells can be sized, shaped, and spaced to be compatible with the pipettor 150. In some embodiments, this can include sizing the wells to be able to receive the pipette tips for aspiration and / or dispensing. In some embodiments, this can further include sizing and spacing the wells such that substance can be simultaneously aspirated from and / or dispensed to a plurality of wells by the multichannel pipettor 150. Thus, in some embodiments, the consumables can include 8 rows of wells that are sized and spaced such that a well in each of the rows can be simultaneously accessed by the pipettor 150.

[0093] The consumables 200 include a sample tube system 202. The sample tube system 202 can be configured to hold one or more samples. The sample tube system 202 can include a sample tube rack 204 and at least one sample tube 206. In some embodiments, and as shown in Figure 6, the sample tube rack 204 can hold multiple sample tubes 206 including, for example, eight sample tubes 206.

[0094] In some embodiments, the sample tube 206 can be configured to hold a sample, and can be received within the sample tube rack 204. The sample tube system 202 is shown in Figure 7.

[0095] The sample tube 206 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the sample tube 206 can comprise a polymer which does not affect the sample. Specifically, in some embodiments, the sample tube 206 can comprise an injection molded polymer. The sample tubes 206 can be sized and shaped so as to hold, for example, between approximately 100 pL and approximately 2 mL, between approximately 2 mL and approximately 20 mL of sample, between approximately 4 mL and approximately 15 mL of sample, between approximately 5 mL and approximately 8 mL a sample, approximately 6 mL of sample, approximately 6.5 mL of sample, approximately 7 mL of sample, proximally 7.5 mL of sample, proximally 8 mL of sample, or any other or intermediate volume of sample. As used herein, “approximately” refers to a range extending + / - 10 percent around the identified number and / or identified range. In some embodiments, the sample tube 206 can have dimensions such that the sample tube 206 can receive 1000 pL pipette tip for aspirating sample from and / or dispensing sample to the sample tube 206.

[0096] The sample tube 206 can, in some embodiments, include an identification feature which can identify the sample tube 206. In some embodiments, the identification feature can uniquely identify the sample tube 206. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the sample tube 206 so as to be readable when the sample tube 206 is coupled to the sample rack 204 and / or received in the proper position 128 in the deck 126 of the system 100.

[0097] In some embodiments, some or all of the sample tubes 206 can include a magnet located in a portion of the sample tube 206. In some embodiments, the magnet can be located in a side of the sample 206. In some embodiments, the magnet can be positioned in the deck 126 and / or the housing such that when the sample tube 206 is received within its position in the deck 126, the magnet is adjacent to a side of the sample tube 206. The magnet can. in some embodiments, be used in pipette tip preconcentration as will be discussed below. The consumables 200 include the lysis-binding plate 208. The lysis-binding plate 208 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the lysis-binding plate 208 can be configured to hold a sample during lysis and binding of the sample. In some embodiments, the lysis-binding plate 208 can include one or several reagents for performing lysis and / or binding, including one or several dried reagents in its wells, and in some embodiments reagents for lysis and / or binding can be from the reagent cartridge.

[0098] The lysis-binding plate 208 can comprise a polymer which does not affect the sample. In some embodiments, the polymer of the lysis-binding plate 208 can be doped with a material having a high thermal conductivity to thereby increase the thermal conductivity of the lysisbinding plate 208. In some embodiments, for example, the polymer of the lysis-binding plate 208 can be doped with metal to increase the thermal conductivity of the lysis-binding plate 208 and to thereby decrease the amount of time required to perform the lysis and binding. Specifically, in some embodiments, the lysis-binding plate 208 can comprise a metal-doped injection molded polymer, such as Makrolon TC621, Makrolon TC 629, Kynar 390, CoolPoly D1202. Coolpoly D5506.

[0099] The lysis-binding plate 208 can comprise a plurality of wells 210 arranged in 8 rows. In some embodiments, the lysis-binding plate 208 can comprise 32 wells 210 arranged in 8 rows of four wells 210. The wells 210, in some embodiments, can be sized and shaped so as to hold, for example, between approximately 2 rnL and approximately 20 mL of sample, between approximately 5 mL and approximately 15 mL of sample, between approximately 8 mL and approximately 12 mL a sample, approximately 8 mL of sample, approximately 8.5 mL of sample, approximately 9 mL of sample, approximately 9.5 mL of sample, approximately 10 mL of sample, approximately 10.5 mL of sample, approximately 11 mL of sample, or any other or intermediate volume of sample. In some embodiments, the wells 210 can have dimensions such that the lysis-binding plate 208 can receive 1000 pL pipette tip for aspirating sample from and / or dispensing sample to the wells 210.

[0100] The lysis-binding plate 208 can, in some embodiments, include an identification feature which can identify the lysis-binding plate 208. In some embodiments, the identification feature can uniquely identify the lysis-binding plate 208. This identification can include identifying that the type of consumable 200. or in other words identify that the lysis-binding plate 208 is a lysis-binding plate 208, or can uniquely identify a specific lysis-bind plate 208 such as. for example, with an identifier that is specific to that lysis-binding plate 208.

[0101] The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the lysis-binding plate 208 so as to be readable when the lysis-binding plate 208 is received in the proper position 128 in the deck 126 of the system 100.

[0102] The consumables 200 include the reagent cartridge 212. The reagent cartridge 212 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the reagent cartridge 212 can be configured to hold substances such as one or several reagents used during the sample preparation. In some embodiments, sample preparation can include operations performed on the sample for DNA extraction, concentration, and purification. These substances can be dry and aqueous. In some embodiments, the substances in the reagent cartridge can be lyophilized and / or oven dried, and can be sealed within one or several compartments of the reagent cartridge 212. In some embodiments, these reagents can include one or several buffers, primers, probes, detergent, or the like.

[0103] In some embodiments, the reagent cartridge 212 can contain and / or contains, in one or more compartments, materials for cell capture and / or processing of samples according to one or more workflows for various applications. As such, the reagent cartridge 212 can define a set of storage volumes distributed across a set of domains, where the set of domains can be configured for providing suitable environments and / or volumetric capacities for the material contents of each domain. The set of storage volumes can directly contain sample processing materials, and / or can alternatively be configured to receive and maintain positions of individual containers (e.g., tubes, etc.) that contain sample processing materials. The storage volumes of each domain can be distributed in arrays, or otherwise arranged. Storage volumes can have circular cross sections, rectangular cross sections, or other morphologies (e.g., cross sections, widths, depths, etc.) depending upon application of use (e.g., cold storage, heat transfer, magnetic separation, etc.).

[0104] The set of domains can additionally or alternatively be configured to provide modularity, where one or more domains can be pre-packaged with materials that are stable over longer shelf lives, while other domains can be configured to receive materials that have short shelf lives (e.g., immediately prior to use). The set of domains can additionally or alternatively be configured to promote operational efficiency (e.g., in relation to grouping similar materials, etc.) for apparatuses of various subsystems described that interact with materials of the reagent cartridge 212. The set of domains can additionally or alternatively define regions for receiving and / or processing material (e.g., nucleic acid material) extracted from the sample.

[0105] Additionally, or alternatively, domains of the set of domains can be separate (e.g., domain for receiving heat is separate from domains that are intended for other storage temperatures or applications requiring different temperatures), overlapping, or otherwise arranged. Domains of the set of domains can additionally or alternatively be distinguished from each other by a morphology (e.g., length of the storage volumes of each domain, depth of storage volumes for accessing or interfacing with other elements of the deck, width or depth of domains configured for efficient heat transfer, etc ). The internal surface properties for certain domains (e.g., for PCR reactions, for magnetic separation, etc.) may be configured with high surface polish to enable low binding or retention of biomolecules (e.g., nucleic acids or proteins). The various domains may also be mixed and matched to provide a variety of available assays to customers or other end-users.

[0106] Individual storage volumes of the set of storage volumes of the reagent cartridge 212 can further include one or more seals, which function to isolate materials within the reagent cartridge 212, to prevent cross-contamination between materials within individual storage volumes, to prevent contaminants from entering individual storage volumes, and / or to prevent evaporative loss during storage and shipment. The seal(s) can be puncturable seal(s) (e.g., composed of paper, composed of a metal foil, and / or composed of any other suitable material). However, the seal(s) can alternatively be configured to be non-puncturable (e.g., the seal(s) can be configured to peel away from the reagent cartridge 212).

[0107] In variations, process materials supported by the domains of the reagent cartridge 212 can include one or more of: buffers (e.g. ethanol, priming buffer, lysis buffer, custom lysis buffers, sample wash buffers, saline with RNAse inhibitors, bead wash buffers, reverse transcription (RT) buffer, etc.), oils (e.g. perfluorinated oil, mineral oil), PCR master mixtures, beads (e.g. functionalized beads) or any other suitable materials used for sample processing, target capture, and / or digital analyses. Additionally, or alternatively, one or more of the set of storage volumes can be empty (e.g., initially empty, empty throughout one or more processes, empty prior to filling by an operator, etc.). Different storage regions in various domains of the reagent cartridge can have initial reagent volumes from a few microliters (e.g., 5 microliters) to 50 milliliters. In some embodiments, for example, the reagent cartridge 212 can contain, a lysis-binding buffer that can include magnetic beads, a wash solution, a protease (e.g., proteinase K), and elution buffer, mineral oil, dPCR buffer, or the like. In some embodiments, the reagent cartridge may contain liquids used for sealing microfluidic reactors such as an Ultra-violet C’U V") curable glue.

[0108] The reagent cartridge 212 can comprise a polymer which does not affect the substances contained within the reagent cartridge 212. In some embodiments, the reagent cartridge 212 can comprise an injection molded poly mer.

[0109] With reference now to Figure 8, a top view of one embodiment of the reagent cartridge 212 is shown. The reagent cartridge 212 can comprise a plurality of storage compartments 214. These storage compartments 214 can be arranged in 8 rows, and thus can include sufficient reagents for sample preparation of eight samples.

[0110] In some embodiments, the reagent cartridge 212 can comprise 96 compartments 214 arranged in 8 rows of 12 compartments 214. The compartments 214, in some embodiments, can be sized and shaped so as to hold, for example, between approximately 0.05 mL and approximately 5 mL of reagents, between approximately 0. 1 mL and approximately 4 mL of reagents, between approximately 0.2 mL and approximately 3 mL of reagents, approximately 0.3 mL of reagents, approximately 1 mL of reagents, approximately 2 mL of reagents, or any other or intermediate volume of reagents. In some embodiments, the compartments 214 can include, in each row of compartments. 4 compartments 214 holding up to 2 mL of reagents, 2 compartments 214 holding up to 1 mL of reagents, and 6 compartments 214 holding up to 0.3 mL of reagents. In some embodiments, the compartments 214 can have dimensions such that the reagent cartridge 212 can receive, for example, 50 pL pipette tips, 1000 pL pipette tips, and / or any other or intermediate pipette tips for aspirating reagents from the compartments 214. In some embodiments, the reagent cartridge may contain compartments for holding extra pipette tips and / or other tools (foil piercing tips, cartridge sealing tips, sleeves) required for specific operations during sample processing.

[0111] The reagent cartridge 212 can, in some embodiments, include an identification feature which can identify the reagent cartridge 212. In some embodiments, the identification feature can uniquely identify the reagent cartridge 212. Thus, in some embodiments, each reagent cartridge 212 can include an identifier that is unique to that reagent cartridge 212, that is unique to a type of reagent cartridge 212 (e.g., unique to the reagents in the reagent cartridge 212), or that is unique to reagent cartridges 212 (e.g., reagent cartridges 212 as a type of consumable 200 have a unique identifier). The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the reagent cartridge 212 so as to be readable when the reagent cartridge 212 is received in the proper position 128 in the deck 126 of the system 100.

[0112] As seen in Figure 6, the consumables 200 include a pipette tip box 216. The pipette tip box 216 can be configured to receive and / or hold one or several pipette tips. The pipette tip box 216 can comprise a variety of shapes and sizes and can be made from a variety of materials. The pipette tip box 216 can comprise a polymer, and in some embodiments, the pipette tip box 216 can comprise a metal-doped injection molded polymer.

[0113] The pipette tip box 216 can comprise a pipette tip tray 218 and a tip box base 220. The pipette tip tray 218 is a roughly planar member with a plurality of thru-holes. Each of the thru-holes can, in some embodiments, be circular thru-holes, each forming a circular-cylinder of removed material through the tip tray 218. In some embodiments, these thru-holes can be sized and shaped such that a pipette tip 222 can be received within the thru-hole and held in place by the thru-hole. In some embodiments, the thru-holes can be sized and shaped such that a pipette tip can be slid into or out of a thru-hole. In some embodiments, the pipette tip tray 218 can define 96 thru-holes, each of which can be configured to receive a 50 pL pipette tip, a 1000 pL pipette tip, and / or any other or intermediate pipette tip. In some embodiments, the tip tray 218 can include 8 rows of thru-holes, each row including 12 thru-holes.

[0114] The pipette tip box base 220 can comprise a box-shaped base having an open top and defining an interior volume. The pipette tip tray 218 can matingly engage with the pipette tip box base 220 such that the pipette tip tray 218 is coupled to the pipette tip box base 220. In some embodiments, and as depicted in Figure 9, one or several pipette tips 222 can extend through one or several of the thru-holes in the pipette tip tray 218. The pipette tip box base 220 can be sized and shaped to define an interior volume such that the pipette tips hang from the pipette tip tray 218 and do not contact each other or a portion of the pipette tip box base The pipete tip box 216 can, in some embodiments, include an identification feature which can identify the tip box 216. In some embodiments, the identification feature can uniquely identify the pipete tip box 216. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag. or the like. In some embodiments, the identification feature can be located on the lysis-binding plate 208 so as to be readable when the pipete tip box 216 is received in the proper position 128 in the deck 126 of the system 100.

[0115] The consumables 200 include a magnetic separation plate 224. The magnetic separation plate 224 can comprise a variety of shapes and sizes and can be made from a variety7of materials. In some embodiments, the magnetic separation plate 224 can be configured to hold a sample during magnetic separation of the sample. The magnetic separation plate 224 can comprise a polymer which does not affect the sample, and in some embodiments, the magnetic separation plate 224 can comprise injection molded polymer.

[0116] The magnetic separation plate 224 can comprise a plurality7of separation wells 226 arranged in 8 rows. In some embodiments, the magnetic separation plate 224 can comprise 96 separation wells 226 arranged in 8 rows of 12 separation wells 226. The separation wells 226, in some embodiments, can be sized and shaped so as to hold, for example, up to approximately 10 mL of sample, up to approximately 8 mL of sample, up to approximately 5 mL of sample, up to approximately 3 mL of sample, up to approximately 2 mL of sample, approximately 1.2 mL of sample, or any other or intermediate volume of sample. In some embodiments, the separation wells 226 can have dimensions such that the magnetic separation plate 224 can receive for example, 50 pL pipete tips, 1000 pL pipete tips, and / or any other or intermediate pipete tips for aspirating reagents from the separation wells 226. In some embodiments, the separation wells 226 and the magnetic separation plate 224 can be compatible with an 8 channel pipettor 150 with pipete tips 222 having, for example, a 9 mm pitch.

[0117] In some embodiments, the magnetic separation plate 224 can be placed in the magnetic separator 134. In some embodiments, the magnetic separator 134 can expose the sample within the separation wells 226 of the magnetic separation plate 224 to a magnetic field. The magnetic field can draw magnetized beads bound to the target in the sample to a wall or a botom of the separation wells 226. With the magnetic beads secured via the magnetic field, the supernatant can be aspirated from the separation wells 226. This can be repeated a desired number of times until a desired amount of magnetic beads and target has been collected in the separation wells 226. In some embodiments, these magnetic beads can be washed one or several times to purify the target bound to the magnetic beads. Upon completion of the washing and purification of the target, the target can be separated from the magnetic beads and collected via elution using the pipettor 150.

[0118] The magnetic separation plate 224 can, in some embodiments, include an identification feature which can identify the magnetic separation plate 224. In some embodiments, the identification feature can uniquely identify' the magnetic separation plate 224. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag. or the like. In some embodiments, the identification feature can be located on the magnetic separation plate 224 so as to be readable when the magnetic separation plate 224 is received in the proper position 128 in the deck 126 of the system 100.

[0119] The consumables 200 include the assay strip 228. The assay strip 228 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the assay strip can comprise a polymer which does not affect the sample. Specifically, in some embodiments, the assay strip 228 can comprise an injection molded polymer. In some embodiments, the polymer of the assay strip 228 can be opaque.

[0120] The assay strip 228 can comprise a plurality of wells, which can be arranged in a plurality of rows. In the embodiment of Figure 6, the assay strip includes 8 rows of wells, each row including two wells. In some embodiments, the wells of the assay strip 228 can hold a volume of between approximately 5 pL and approximately 10 pL of dried reagent or any other or intermediate volume of dried reagents. In some embodiments, each well can have a mixing volume of between approximately 10 pL and 30 pL. a mixing volume of approximately 20 pL, or any other or intermediate mixing volume.

[0121] The wells in the assay strip can be sized and shaped to receive a pipette tip 222. In some embodiments, this pipette tip 222 can comprise a 50 pL pipette tip which can have, for example, a 9 mm pitch. In some embodiments, the wells of the assay strip 228 can have clearance for the pipette tip 222 to aspirate and / or dispense sample into or from the wells. In some embodiments, the wells of the assay strip 228 can be sealed. The wells can be sealed, in some embodiments, using a penetrable seal that can be a metal and / or metallized seal. In some embodiments, the wells can be sealed with an aluminum seal.

[0122] In some embodiments, the assay strip 228 can be configured and / or can hold one or several dried reagents. These reagents can, in some embodiments be lyophilized and / or oven dried. These dried reagents can be specific to a desired assay, or can be generally useable reagents. In some embodiments, these reagents can include master mix, one or several primers, one or several enzymes, and / or one or several probes.

[0123] In some embodiments, the master mix can be specific to the assay being performed and / or to a step being performed. The master mix can include, for example, a pre-amplification master mix, a fetal fraction master mix, a NIPT master mix, and / or any other master mix.

[0124] In some embodiments, the composition and / or concentration of the dried reagents in the assay strip can vary based on the PCR chip, for example based on whether the PCR chip includes mi crowells. or if the PCR chip is configured for droplets.

[0125] The assay strip 228 can, in some embodiments, include an identification feature which can identify the assay strip 228. In some embodiments, the identification feature can uniquely identify the assay strip 228. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the assay strip 228 so as to be readable when the assay strip 228 is received in the proper position 128 in the deck 126 of the system 100.

[0126] The consumables 200 include the DNA quantification strip 230. also referred to herein as a DNA quant strip 230. The DNA quant strip 230 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the DNA quant strip 230 can comprise a polymer which does not affect the sample. Specifically, in some embodiments, the DNA quant strip 230 can comprise an injection molded polymer. In some embodiments, the polymer of the DNA quant strip 230 can be opaque.

[0127] The DNA quant strip 230 can comprise a plurality of wells, which can be arranged in a plurality or rows. In the embodiment of Figure 6, the assay strip includes 8 rows of wells, each row including one well. In some embodiments, the wells of the DNA quant strip 230 can hold a volume of between approximately 5 pL and approximately 10 pL of dried reagent or any other or intermediate volume of dried reagents. In some embodiments, for example, a cake of dried reagents can take up space equivalent to a volume corresponding to any of the above identified volumes and / or ranges of volumes. In some embodiments, each well can have a mixing volume of between approximately 10 pL and 30 pL, a mixing volume of approximately 20 pL, or any other or intermediate mixing volume.

[0128] The wells in the DNA quant strip 230 can be sized and shaped to receive a pipette tip 222. In some embodiments, this pipette tip 222 can comprise a 50 pL pipette tip which can have, for example, a 9 mm pitch. In some embodiments, the wells of the DNA quant strip 230 can have clearance for the pipette tip 222 to aspirate and / or dispense sample into or from the wells. In some embodiments, the wells of the DNA quant strip 230 can be sealed. The wells can be sealed, in some embodiments, using a penetrable seal that can be a metal and / or metallized seal. In some embodiments, the wells can be sealed with an aluminum seal.

[0129] In some embodiments, the DNA quant strip 230 can, in some embodiments, be configured and / or can hold one or several dried reagents. Alternatively, in some embodiments, the reagents for performing DNA quantification can be located in the reagent cartridge 212. These reagents can, in some embodiments be lyophilized and / or oven dried. These dried reagents can be specific to DNA quantification and can include, for example, one or several primers, and / or one or several probes. In some embodiments, these reagents can include, for example, fluorescent dye and one or several excipients such as, for example, trehalose.

[0130] The DNA quant strip 230 can, in some embodiments, include an identification feature which can identify the DNA quant strip 230. In some embodiments, the identification feature can uniquely identify the DNA quant strip 230. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the DNA quant strip 230 so as to be readable when the DNA quant strip 230 is received in the proper position 128 in the deck 126 of the system 100.

[0131] The consumables 200 include the pre-amplification strip 232, also referred to herein as a preamp strip 232. The pre-amp strip 232 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the pre-amp strip 232 can comprise a polymer which does not affect the sample. Specifically, in some embodiments, the pre-amp strip 232 can comprise an injection molded polymer. In some embodiments, the polymer of the pre-amp strip 232 can be opaque.

[0132] The pre-amp strip 232 can comprise a plurality of wells, which can be arranged in a plurality of rows. In the embodiment of Figure 6, the pre-amp strip 232 includes 8 rows of wells, each row including one well. In some embodiments, some or all of the wells of the pre-amp strip 232 can include reagents for use in the preamplification, and in some embodiments, these reagents can be taken from the reagent cartridge 212. In some embodiments, the wells of the pre-amp strip 232 can hold a volume of between approximately 1 pL and approximately 20 pL of dried reagent, between approximately 5 pL and approximately 10 pL of dried reagent or any other or intermediate volume of dried reagents. In some embodiments, for example, a cake of dried reagents can take up space equivalent to a volume corresponding to any of the above identified volumes and / or ranges of volumes. In some embodiments, each well can have a mixing volume of between approximately 1 pL and 40 pL, of between approximately 10 pL and 30 pL, a mixing volume of approximately 20 pL, or any other or intermediate mixing volume.

[0133] The wells in the pre-amp strip 232 can be sized and shaped to receive a pipete tip 222. In some embodiments, this pipete tip 222 can comprise a 50 pL pipete tip, a 1000 pL pipette tip, or any other or intermediate volume pipete tip 150 which can have, for example, a 9 mm pitch. In some embodiments, the wells of the pre-amp strip 232 can have clearance for the pipete tip 222 to aspirate and / or dispense sample into or from the wells. In some embodiments, the wells of the pre-amp strip 232 can be sealed. The wells can be sealed, in some embodiments, using a penetrable seal that can be a metal and / or metallized seal. In some embodiments, the wells can be sealed with an aluminum seal.

[0134] In some embodiments, the pre-amp strip 232 can be configured and / or can hold one or several dried reagents or one or several liquid reagents. These reagents can, in some embodiments be lyophilized and / or oven dried. These dried reagents can be specific to preamplification and can include, for example, one or several primers, one or several enzymes, and / or one or several probes.

[0135] The pre-amp strip 232 can, in some embodiments, include an identification feature which can identify the pre-amp strip 232. In some embodiments, the identification feature can uniquely identify the pre-amp strip 232. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag. or the like. In some embodiments, the identification feature can be located on the pre-amp strip 232 so as to be readable when the pre-amp strip 232 is received in the proper position 128 in the deck 126 of the system 100.

[0136] The consumables 200 include the PCR chip 234, also referred to herein as a PCR cartridge 234. The PCR chip 234 can be configured to hold a plurality of partitions for thermocycling and imaging. These partitions can be in the form of a plurality of microwells, or in the form of microdroplets. The partitions can all be of the same size or a series of different but predetermined volumes to mimic serial dilutions. In some embodiments, these droplets can be water in oil droplets. In some embodiments, some or all of the partitions can contain nucleic acids and fluorescent dyes that produce signal in the presence of a target or any nucleic acid.

[0137] The partitions can each have a volume of, for example, less than 10 microliters or less than 1 microliter, or less than 100 nanoliters or less than 10 nanoliters, or less than 1000 picoliters, less than 400 picoliters, less than 300 picoliter, less than 200 picoliters, less than 100 picoliters, less than 50 picoliters, between approximately 10 picoliters and approximately 1000 picoliters, between approximately 125 picoliter and 200 picoliter, a volume of approximately 180 picoliters, or any other or intermediate volume.

[0138] The PCR chip 234 can comprise a variety of shapes and sizes and can be made from a variety of materials. The PCR chip 234 can comprise a polymer that allows imaging and thermocycling of the partitions. In some embodiments, all or portions of the PCR chip 234 can be optically transparent to facilitate data acquisition. This can include, for example, one or both of the top and the bottom of the PCR chip 234 being optically transparent. In some embodiments, the PCR chip 234 can comprise one or several flat or smooth surfaces configured to be engaged by the suction cups of the pipettor 150 to thereby enable the automated movement of the PCR chip 234 to different locations in the system 100.

[0139] The PCR chip 234 can. in some embodiments, comprise a Cyclin Olefin Polymer that can withstand heating up to 120 °C, and to withstand cycling through temperatures from approximately 4 °C to approximately 98 °C. In some embodiments, the PCR chip 234 can have a chip configured to enable imaging, including, for example, one or more surfaces through which imaging occurs having an SPIA2 finish. In some embodiments, for example, one or both of a top and a bottom of the PCR chip 234 can have a SPIA2 finish. In some embodiments, the PCR chip 234 polymer can be selected to have low autofluorescence in the excitation frequencies used by the imager. The material of the PCR chip may be doped with materials such as carbon, boron nitirde, or aluminum nitride to improve the thermal conductivity of the material.

[0140] The PCR chip 234 can comprise a number of regions for performing different assays. In some embodiments, these regions can include a first region for performing a first assay, a second region for performing a second assay, a third region for performing a third assay, and a fourth region for performing a fourth assay. In some embodiments, these regions can be arranged into groups, such that, for a sample, the PCR chip 234 includes a plurality of groups, each of which groups includes a first region, a second region, a third region, and / or a fourth region. In some embodiments, a PCR chip 234 can include 8 groups, allowing the PCR chip 234 to simultaneously contain partitions from 8 samples and simultaneously perform thermocycling and / or imaging on up to 8 samples.

[0141] The first region can be configured for receiving partitions to perform a first assay. In some embodiments, this first assay can comprise an NIPT assay. Each of the first regions can have an assay volume of, for example, up to 40 pL, up to 30 pL, up to 20 pL, between approximately 5 pL and approximately 20 pL. of approximately 15 pL. or any other or intermediate volume. Each of the first regions on the PCR chip 234 can be configured to receive a plurality of partitions, and specifically between 1 and 1000 partitions, and specifically between 1000 and 10,000 partitions and specifically between 10,000 and 50,000 partitions. and specifically between approximately 50,000 partitions and approximately 500,000 partitions, between approximately 100,000 partitions and approximately 400,000 partitions, between approximately 150,000 partitions and approximately 300,000 partitions, approximately 200,000 partitions, or any other or intermediate number of partitions. In some embodiments, this can include the first region including structure such as one or several microwells for receiving the desired number of partitions. In some embodiments, each microwell can comprise a rectangular shape having an open top having a length of 40 microns, a width of 40 microns, and a depth of 60 microns. Such a microwell can hold, for example, 96 picoliters.

[0142] The second region can be configured for receiving partitions to perform a second assay. In some embodiments, this second assay can comprise a Fetal Fraction assay. Each of the second regions can have an assay volume of, for example, up to 30 pL, up to 20 pL, up to 15 pL, up to 10 pL, between approximately 5 pL and approximately 10 pL, of approximately 8 pL, or any other or intermediate volume. Each of the second regions on the PCR chip 234 can be configured to receive a plurality of partitions, and specifically between approximately 10,000 partitions and approximately 500,000 partitions, between approximately 20,000 partitions and approximately 250,000 partitions, between approximately 50,000 partitions and approximately 150,000 partitions, approximately 100,000 partitions, or any other or intermediate number of partitions. In some embodiments, this can include the second region including structure such as one or several microwells for receiving the desired number of partitions.

[0143] The third region can be configured for receiving partitions to perform a third assay. In some embodiments, this third assay can comprise a control assay. Each of the third regions can have an assay volume of. for example, up to 15 pL, up to 10 pL, up to 5 pL, between approximately I pL and approximately 5 pL, of approximately 3 pL, or any other or intermediate volume. Each of the third regions on the PCR chip 234 can be configured to receive a plurality of partitions, and specifically between approximately 1,000 partitions and approximately 100,000 partitions, between approximately 5,000 partitions and approximately 50,000 partitions, between approximately 10,000 partitions and approximately 30,000 partitions, approximately 20,000 partitions, or any other or intermediate number of partitions. In some embodiments, this can include the third region including structure such as one or several microwells for receiving the desired number of partitions.

[0144] The fourth region can be configured for receiving partitions to perform a fourth assay. In some embodiments, this fourth assay can comprise a DNA quantification assay. Each of the fourth regions can have an assay volume of, for example, up to 50 pL, up to 30 pL, up to 25 pL, between approximately 101 pL and approximately 30 pL, of approximately 20 pL, or any other or intermediate volume. In some embodiments, each of the fourth regions on the PCR chip 234 can comprise a single well, also referred to herein as a quantification well, or as a quant well.

[0145] In some embodiments, each of the first regions 252 and each of the second regions 256 is bounded by a moat 257. The moat 257 can prevent sample from one region 252, 256 from inadvertently entering into another region 252, 256. Thus, the moats 257 can divide microwell areas of different samples and / or reaction type. In other embodiments, one part of a region is bounded by a moat 257 and another part of the same region is bounded by a moat 257. In other embodiments, one or more regions are bounded by a moat 257. In some embodiments, the moat 257 can have a volume of between approximately 1 pL and approximately 5 pL, a volume of approximately 2 pL. or any other or intermediate volume.

[0146] In some embodiments, the PCR chip 234 can be sized, shaped, and / or configured such that sample can be dispensed to the different features of the PCR chip 234. In some embodiments, for example, the PCR chip 234 can receive sample from a 50 pL pipette tip, and specifically from a 50 pL filtered pipette tip. In some embodiments, the PCR chip 234 can be sized, shaped, and / or configured to receive sample from a multichannel pipettor 150, including an 8 channel pipettor 150, which can have, for example, a 9 mm pitch.

[0147] The PCR chip 234 can comprise a microwell cartridge 233 or droplet cartridge 235. One embodiment of a PCR chip 234 that is a microwell cartridge 233 is show n in Figure 10. The PCR chip 234 includes first rows 250 including a plurality of first regions 252 (16 first regions are depicted in Figure 10), a second row 254 including second regions 256 (8 second regions are depicted in Figure 10), and a plurality of quant wells 258 (8 quant wells are depicted in Figure 10). Each of the first regions 252 and the second regions 256 comprise a plurality' of microwells, with one microyvell per partition. Thus, a region configured for 100,000 partitions has 100.000 micro wells.

[0148] As shown on the microwell cartridge 233, the PCR chip 234 further includes an identifier region 260 which can include an identification feature that can identify the PCR chip 234. In some embodiments, the identification feature can uniquely identify the PCR chip 234. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag. or the like. In some embodiments, the identification feature can be located on the PCR chip 234 so as to be readable when the PCR chip 234 is received in PCR cartridge holder 160 on the deck 126 of the system 100.

[0149] Figure 11 is a depiction of a droplet cartridge 235. The droplet cartridge 235 includes a first row 250 including a plurality of first regions 252 (8 first regions are depicted in Figure 11), a second row 254 including second regions 256 (8 second regions are depicted in Figure 1 1), and a plurality of quant wells 258 (8 quant wells are depicted in Figure 11). Each of the first regions 252 and the second regions 256 comprise volume loadable with a plurality of droplets, each droplet forming a partition. Thus, a region configured for 100,000 partitions can receive 100,000 droplets. The embodiment of Figure 11 includes a third row 253 including a plurality of third regions

[0150] 255 (8 third regions are depicted in Figure 11). The third regions 255 can be control regions for performing a control assay. Each of the third regions 255 comprise a volume loadable with a plurality of droplets, each droplet forming a partition. Thus, a third region 255 configured for 100,000 partitions can receive 100,000 droplets. Droplets required for filling of these reactors could be generated by a variety of methods such as microfluidic t-j unctions bringing oil and aqueous reagents into the t-j unction, or using multiple picohter dispensing nozzles or using vibration or agitation induced emulsification of aqueous solutions in oil. Each of the regions 252, 255, 256 includes an inlet whereby droplets can be loaded via pipettor 150 into that region 252. 255, 256. Thus, first regions 252 include a first inlet 264. In some embodiments, each first region 252 includes its own, unique first inlet 264. Similarly, second regions 256 include a second inlet 266. In some embodiments, each second region

[0151] 256 includes its own, unique second inlet 266. Further, third regions 255 include a third inlet 265. In some embodiments, each third region 255 includes its own, unique third inlet 265. Each of these inlets 264, 265, 266 can sealingly engage with a pipette rip 222 when the pipette tip 222 is pressed into the inlet 264, 265. 266 with between approximately 1 pound and approximately 10 pounds of force, with approximately 5 pounds of force, or with any other or intermediate amount of force. In some embodiments, and upon completion of loading of one or all of the regions 252, 255. 256 of the droplet cartridge 235. the inlets 264, 265, 266 can be sealed. In some embodiments, these inlets can be sealed via an adhesive that can be, for example, a curable adhesive such as a UV curable glue.

[0152] Upon completion of loading and sealing of the droplet cartridge 235, the droplet cartridge 235 and the droplets contained therein can be thermocycled. In doing so, the thermocycler can push against a top surface 269 of the PCR chip 234, and in the embodiment of Figure 11. the top surface 269 of the droplet cartridge 235, and in some embodiments, can apply a pressure of at least 3 psi across the entire thermocycling area. To facilitate the thermocycling, in some embodiments, the top layer of the droplet cartridge 235 can have a thermal resistance equivalent to a 1 mm thick layer at 1 W / m-K or more (example 10 W / mK) or 0.5mm thick layer at 0.25 W / mK. In some embodiments, the droplet cartridge 235 can include a pressurizing plunger 268 that can, during thermocycling, be engaged by the thermocycler to increase pressure inside of the regions 252, 255, 256 by a desired amount which can be up to 10 psi, up to 5 psi. up to 3 psi, to between 0.5 psi and 3 psi, to approximately 2 psi, or any other or intermediate pressure. In some embodiments, the pressurizing plunger 268 can remain compressed during some or all of the thermocycling.

[0153] Like the microwell cartridge 233, the droplet cartridge 235 further includes an identifier region 260 which can include an identification feature that can identify the droplet cartridge 235. In some embodiments, the identification feature can uniquely identify the droplet cartridge 235. The identification feature can include, for example, a computer readable code such as. for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the droplet cartridge 235 so as to be readable when the droplet cartridge 235 is received in PCR cartridge holder 160 on the deck 126 of the system 100.

[0154] The consumables 200 include the PCR chip lid 236. In embodiments in which the PCR chip 234 is the microwell cartridge 233, the PCR chip lid 236 can be configured for sealingly coupling to the PCR chip 234 to seal the microwells. In some embodiments, for example, the PCR chip lid 236 can be configured to engage with the PCR chip 234 when the PCR chip lid 236 is placed on top of the PCR chip 234. The PCR chip lid 236 can be pressed down on the PCR chip 234, which can result, in some embodiments, in the PCR chip lid 236 irreversibly engaging with the PCR chip 234. In some embodiments, the PCR chip lid 236 can be applied to the PCR chip, and suction is applied via the pipettor 150. This suction can engage and / or sealingly engage the PCR chip lid 236 and the PCR chip 234. In some embodiments, the thermocycler can compress the PCR chip lid 236 on the PCR chip 234. In some embodiments, this compression can be performed while heating the PCR chip lid 236. In some embodiments, this combination of pressure and heat can sealingly couple the PCR chip lid 236 and the PCR chip 234. In some embodiments, and when sealingly applied to the PCR chip 234, the PCR chip lid 236 can seal each of the microwells of the PCR chip 234. In some embodiments, the PCR chip lid can be engaged irreversibly into the PCR chip by pushing the suction cup tool such that clamps or living hinge present on the side of the PCR chip lid latches onto the PCR chip lid.

[0155] The PCR chip lid 236 can comprise a variety of shapes and sizes and can be made of a variety of materials. In some embodiments, the PCR chip lid 236 is sized to be sufficiently large to seal the PCR chip 234. and in some embodiments, the PCR chip lid 236 has a thickness to facilitate heat transfer and to prevent optical interference w ith imaging. In some embodiments, the PCR chip lid 236 has a thickness of up to approximately 3 mm, up to approximately 2 mm. up to approximately 1 mm, of approximately 1 mm, or any other or intermediate thickness. The PCR chip lid may also be made of different composite layers such as combination of a thermally conductive material (0.25 mm- 2 mm thick) with an elastomeric layer (0.2 mm - 1mm thick).

[0156] In some embodiments, the PCR chip lid 236 can comprise an elastomeric material that is PCR compatible and that creates a thermal interface with the thermocycler. In some embodiments, the thermal interface has a maximum thermal resistance equivalent to a 1 mm thick layer at 1 W / m-K. In some embodiments, the elastomeric material of the PCR chip lid 236 can have a thermal conductivity of from approximately 0.25 W / m-K to approximately 10 W / m — K, or any other or intermediate thermal conductivity. In some embodiments, the PCR chip lid 236 can withstand cycling through temperatures from approximately 4 °C to approximately 98 °C, and in some embodiments, the PCR chip lid 236 material can be selected to have low autofluorescence in the excitation frequencies used by the imager.

[0157] The PCR chip lid 236 is shown in Figure 10. The PCR chip lid 236 includes an identifier region 262 which can include an identification feature that can identify the PCR chip lid 236. In some embodiments, the identification feature can uniquely identify the PCR chip lid 236. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag, or the like. In some embodiments, the identification feature can be located on the PCR chip lid 236 so as to be readable when the PCR chip lid 236 is received in PCR cartridge lid holder 162 on the deck 126 of the system 100.

[0158] The consumables 200 include the RNA strip 270. The RNA strip 270, shown in Figure 12, can comprise a variety of shapes and sizes and can be made from a variety' of materials. In some embodiments, the assay strip can comprise a polymer that is compatible with the sample and that is thermally conductive. Specifically, in some embodiments, the RNA strip 270 can comprise an injection molded polymer that can be a polymer selected for high thermal conductivity, or that can be doped with a material to increase the thermal conductivity of the polymer. In some embodiments, for example, the polymer of the RNA strip 270 can be doped with metal to increase the thermal conductivity of the RNA stnp 270. In some embodiments, the polymer of the assay strip 228 can be opaque. The RNA strip 270 can comprise a plurality of wells 272. In the embodiment of Figure 12, the RNA strip 270 includes 8 rows of wells 272. each row including one well 272. In some embodiments, the wells 272 of the RNA strip 270 can hold a volume of up to 10 mL, up to 5 mL between approximately 2 mL and approximately 6 mL, approximately 4 mL, or any other or intermediate volume.

[0159] The wells in the RNA strip 270 can be sized and shaped to receive a pipette tip 222. In some embodiments, this pipette tip 222 can comprise a 50 pL pipette tip, a 1000 pL pipette tip, or any other or intermediate pipette tip 222. In some embodiments, the RNA strip 270 can be compatible with pipettor 150 and / or with a pipettor 150 and / or pipette tip 222 which can have, for example, a 9 mm pitch.

[0160] The RNA strip 270 can, in some embodiments, include an identification feature which can identify the RNA strip 270. In some embodiments, the identification feature can uniquely identify the RNA strip 270. The identification feature can include, for example, a computer readable code such as, for example, a barcode, a 2D barcode such as a data matrix code or a QR code, and alphanumeric code, and electronic identifier such as a radiofrequency identifier (RFID) tag. or the like. In some embodiments, the identification feature can be located on the RNA strip 270 so as to be readable when the RNA strip 270 is received in the RNA heater 138.

[0161] In some embodiments, the dimensions, and specifically the volumes of wells in the system 100 can be harmonized to facilitate DNA transfer from the assay strip 228 to the PCR chip 234. Specifically, this can include harmonizing the volumes of wells of the assay strip 228 to the volume of the PCR chip 234. In some embodiments, for example, this harmonizing comprises having at least one well of the assay strip having the same volume as the total volume of the wells in the PCR chip 234 that will receive the final reaction mix from the one well of the assay strip 228. In some embodiments, this harmonization can enable the transfer of the majority of DNA from the assay strip 228 to the PCR chip 234. In some embodiments, for example, this can include transferring at least 50% of the DNA from the assay strip 228 to the PCR chip 234.

[0162] With reference now to Figure 13, a schematic depiction of control of one embodiment of the system 100 is shown. As seen, the system 100 includes a controller 300. The controller 300 can be configured to receive communications from one or several components of the system 100 and to generate control signals controlling operation of those one or several components of the system 100. The controller 300 can comprise a computing device, and specifically can comprise and / or be at least one processor communicatively coupled with memory’ 302. The memory 302 can comprise stored instructions in the form of computer code, that when executed by the processor and / or the controller 300, cause the processor and / or controller 300 to take one or several actions. The memory' 302 can comprise primary and / or secondary' memory’. The memory 302 can include, for example, cache memory, RAM. ROM, PROM, EPROM. EEPROM, one or several solid-state drives (SSD), one or several hard drives or hard disk drives, or the like. Thus, in some embodiments, the memory' 302 can include volatile and / or non-volatile memory.

[0163] The processor can include one or several microprocessors, such as one or several Central Processing Units (CPUs) and / or one or several Graphics Processing Units (GPUs). The processor can be a commercially available microprocessor from Intel®. Advanced Micro Devices, Inc ®, Nvidia Corporation ®, or the like.

[0164] The controller 300 can be communicatively connected with each of the pre-amplifi cation thermocycler 130, the shaker / heater 132, the magnetic separator 134, the chiller 136, the RNA heater 138, and / or the chip tray 144. The controller 300 can receive signals from each of these components and can generate control signals controlling the operation of these components. In some embodiments, this can include generating control signals controlling heaters of, for example, the pre-amplification thermocycler 130, the heater / shaker 132, the chiller 136, and / or the RNA heater 138. In some embodiments, the control signals generated by the controller 300 can control the opening and / or closing of the chip tray 144. In some embodiments, these control signals generated by the controller 300 can be coordinated such that one or several of these components operate serially, in parallel, and / or partially in parallel.

[0165] The controller 300 is communicatively coupled with a display 304. The display 304 can comprise a screen or monitor. In some embodiments, the display 304 can comprise a touch screen. The display 304 can be configured to provide outputs to the user and can be configured to receive inputs provided from the user and provide those received inputs to the controller 300. In some embodiments, the display 304 can provide outputs to the user of the system 100 and or several input features such as, for example, one or several keyboards, keypads, mouses, microphones, buttons, or the like can provide inputs from the user to the system 100. As further seen in Figure 13, the controller 300 is communicatively coupled with the thermocycler 306 and the imager 308. The imager 308 and the thermocycler 306 are components of the reader module 124. In some embodiments, the thermocycler 306 and the image 308 can be combined into a single module within the reader module 124. The thermocycler 306 can be configured to cyclically heat and cool partitions in the PCR chip 234, and comprise, in some embodiments, a heater. In some embodiments, control signals generated by the controller 300 can control the thermocycler 306 to control the number of cycles applied to partitions in the PCR chip 234, to control the temperatures of the cycles applied to the partitions in the PCR chip 234, to control the duration of the cycles applied to the partitions in the PCR chip 234, or to control any other aspect of the thermocycling of the partitions in the PCR chip 234.

[0166] In some embodiments, the controller 300 can further control the thermocycler 306 to pressurize the PCR chip 234 and / or to couple the PCR chip lid 236 to the PCR chip 234. In some embodiments, the controller 300 can further control the thermocycler 306 to sealingly couple the PCR chip lid 236 to the PCR chip 234. To control these operations of the thermocycler 306, the controller 300 can generate control signals controlling the relative position of the thermocycler 306 with respect to the PCR chip 234 and / or the PCR chip lid 236, and / or controlling manipulation of the pressurizing plunger 268 of the PCR chip 234.

[0167] In some embodiments, the imager 308 can be configured to generate images of one or several PCR chips 234 within the reader module 124. In some embodiments, this can include generating a single image comprising the entire PCR chip 234 and in other embodiments, this can include generating multiple images of different areas of the PCR chip 234 that, together, form one image comprising the entire PCR chip 234. This image can have sufficient resolution such that each partition in the PCR chip 234 can be individually resolved. In some embodiments, this image can have sufficient resolution such that each partition in the PCR chip 234 can be individually resolved by a plurality of pixels in the image.

[0168] In some embodiments, the controller 300 can analyze images received from the imager 308. This analysis will be discussed in greater detail below, but can include automatic identification of pixels belonging to partitions, image normalization, and automatic identification of monolayer partitions. In some embodiments, this analysis can be performed at least partially via one or several artificial intelligence classifiers and / or machine learning models. In some embodiments, these classifiers and / or models can be trained to generate a prediction of a probability of an outcome based on inputs received by the classifiers and / or models.

[0169] The imager 308 can be configured to illuminate the PCR chip 234 with excitation energy and to capture one or several images of the PCR chip 234 and / or detect light emitted by the PCR chip 234. In some embodiments, the imager 308 can include one or several excitation sources 310. These excitation sources 310 can comprise, for example, one or several lightbulbs, LEDs, or any other source of excitation energy . In some embodiments, these excitation sources 310 can include one or several filters configured to ensure that excitation energy illuminating the PCR chip 234 is of a desired frequency and / or wavelength. In some embodiments, the imager 308 can be configured to eliminate the PCR chip 234 with six frequencies of electromagnetic energy. These six frequencies of electromagnetic energy’ for excitation are referred to herein as six channels of excitation energy.

[0170] The imager 308 can include an image capture feature 312, which image capture feature 312 can include one or several light detection features. In some embodiments, the image capture feature 312 can include one or several filters configured to ensure that the image capture feature 312 captures images of the PCR chip 234 of desired frequencies of light and / or captures desired frequencies of light emitted by the PCR chip 234 and more specifically by the partitions in the PCR chip 234. In some embodiments, the image capture feature 312 can be configured to capture different sets of frequencies for each of the six channels of excitation energy. The imager may capture images from the PCR chip at the beginning of the thermocycling, at the end of thermocycling and or any cycles in between the start and end of thermocycling. Special protocols such as melting programs may also be done where the thermocycled material is heated continuously from room temperature to denature temperature (examples 95 C) in a continuous fashion ( 0.1 C / s or 0.5 C / s or 1 C / s ) or in discrete steps and the PCR product imaged to predict the melting points of PCR constituents. Instead of heating from room temp to 95 C. the protocol may be run by cooling from 95C to room temperature.

[0171] The controller 300 can be communicatively coupled to the pipettor 150. The pipettor 150, as shown in Figure 13, comprises a plurality of components that can be controlled by and / or be affected by control of the controller 300. As previously discussed, the pipettor 150 is moveably coupled to the gantry 156. which moves on tracks 158. The gantry 156 is movable along the tracks 158 via x-motor 314. The x-motor 314 can comprise any desired motor and / or actuator including, for example, a stepper motor, a linear actuator, or the like. In some embodiments, the x-motor 314 can drive a belt which can be coupled to the gantry and the movement of which belt can move the gantry 156 either in a positive x-direction or in the negative x-direction along the tracks 158.

[0172] The pipettor 150 includes a pipettor body 316. The pipettor body 316 is movable above and across the deck 126 of the system 100. The pipettor body 316 is movably coupled to the gantry’ 156. The pipettor body 316 is movably coupled to the gantry 156 viay-motor 318. The y-motor 318 can comprise any desired motor and / or actuator including, for example, a stepper motor, a linear actuator, or the like. In some embodiments, the y-motor 318 can drive a belt which can be coupled to the pipettor body 316, and the movement of which belt can move the pipettor body 316 in either a positive y-direction or in a negative y-direction along the gantry 156.

[0173] Each of the x-motor 314 and the y-motor 318 are communicatively coupled to the controller. Via this communicative coupling, the controller 300 can determine, tracks, and / or monitor the location of the pipettor 150, and can generate one or several control signals controlling operation of the x-motor 314 and the y-motor 318 to move the pipettor 150 to a desired location.

[0174] The pipettor body 316 can be movably coupled to a pipettor assembly 320. The pipettor assembly 320 is movably coupled to the pipettor body 316. Specifically, in some embodiments, the pipettor assembly 320 is movable in the z-axis with respect to the pipettor body 316. In some embodiments, this can include the movement of the pipettor assembly 320 from a first position at a first vertical distance with respect to the deck 126 to a second position at a second vertical position with respect to the deck 126. In some embodiments, for example, the first vertical distance from the deck 126 can be greater than the second vertical distance from the deck 126. In some embodiments, the pipettor assembly 320 can be moved to the first position at the first vertical distance from the deck 126 when the pipettor assembly 320 is moved above and across the deck, and the pipettor assembly can be moved to the second position at a second vertical distance from the deck 126 when the pipettor assembly 320 is used and / or about to be used for pipetting operation including for example, aspiration, or dispensing.

[0175] In some embodiments, the pipettor assembly 320 is movable with respect to the pipettor body 316 via z-motor 322. The z-motor 322 can comprise any desired motor and / or actuator including, for example, a stepper motor, a linear actuator, or the like. In some embodiments, the z-motor 322 can drive a belt which can be coupled to the pipettor assembly 320, and the movement of which belt can move the pipettor assembly in either a positive z-direction or in a negative z-direction along the pipettor body 316.

[0176] The pipettor assembly 320 includes or is coupled to a sensor 324. The sensor 324 can be configured to determine a position of the pipettor assembly 320 with respect to the deck 126, and specifically to determine a distance from the pipettor assembly 320 to the deck 126. The sensor 324 can comprise any one or several sensors or features configured to determine a location of the pipettor assembly 320 with respect to the deck 126 and specifically to determine a distance from the pipettor assembly 320 to the deck 126. In some embodiments, sensor 324 can comprise, for example, a proximity sensor, an ultrasonic sensor, an infrared distance sensor, a laser distance sensor (LIDAR), an LED time-of-flight distance sensor, or the like. The sensor 324 can be communicatively coupled with the controller 300, and can provide such information to the controller 300.

[0177] The z-motor 322 is communicatively coupled to the controller 300. Via this communicative coupling, the controller 300 can determine, track, and / or monitor the location of the pipettor assembly 320 with respect to the deck 126 and / or with respect to the pipettor body 316. In some embodiments, the controller can determine, track, and / or monitor the location the pipettor assembly 320 with respect to the deck 126 based on information received from the sensor 324. The controller 300 can generate one or several control signals controlling operation of the z-motor 322 to move the pipettor assembly 320 to a desired location and / or in a desired direction.

[0178] The pipettor assembly 320 can include a support 326. The support 326 can be a structural member to which a plurality of dispense heads 328 are coupled. In some embodiments, the pipettor 150, and specifically the pipettor assembly can include 1 dispense head 328, 2 dispense heads 328, 3 dispense heads 328, 4 dispense heads 328, 5 dispense heads 328. 6 dispense heads 328, 7 dispense heads 328, 8 dispense heads 328, 9 dispense heads 328, 10 dispense heads 328, 15 dispense heads 328, 20 dispense heads 328, any other or intermediate number of dispense heads 328.

[0179] Each of the dispense heads 328 is configured for matingly engage with and fluidly couple to a pipette tip 222, and specifically can couple to a proximal end 329 of the pipette tip 222 such that a distal end 331 of the pipette tip 222 extends below the dispense heads 328 and towards the deck 126. Each of the dispense heads 328 are further fluidly coupled via a manifold 330 to a pump 332. The manifold 330 can be a controllable manifold 330. and specifically can include one or several valves controllable by the controller 300 to selectively couple the dispense heads 328 to the pump 332. In some embodiments, the controller 300 can selectively couple one or more dispense heads 328 to the pump 332 via the manifold 330.

[0180] The pump 332 can be configured to generate a vacuum to cause aspiration via the pipette tip 222 and / or generate pressure to cause dispensing via the pipette tip 222. The pump 332 can be communicatively coupled to the controller 300. The controller 300 can receive information from the pump 332 relating to the operation of the pump 332 and / or to one or several operating parameters of the pump 332, and the controller 300 can generate one or several control signals controlling operation of the pump 332.

[0181] The pipettor assembly 320 can further include, or further be coupled to a scanner 334. The scanner 334 can be configured to read identification features of the one or several consumables 200. In some embodiments, the scanner 334 can comprise, for example, a camera, a barcode reader, an electronic reader such as an RFID tag reader, or the like. The scanner 334 can be communicatively coupled to the controller 300 such that the scanner is responsive to control signals received from the controller 300. and provides outputs to the controller 300. In some embodiments, for example, the controller 300 can cause the scanner 334 to scan the identification feature of one or several consumables 200, and the scanner 334 can provide that information to the controller 300. Based on the information received from the scanner 334, the controller 300 can identify the consumable associated with the identification feature and / or can identify one or several attributes of that consumable. In some embodiments, and in combination with knowing the position of the pipettor 150, the controller 300 can determine whether the identified consumable 200 is in its correct position 128 on the deck 126.

[0182] The pipettor 150 further includes a drip tray assembly 336. The drip tray assembly 336 can be configured to deploy a drip tray under the pipettor 150 and under distal ends 331 of the pipette tips 222 to prevent drops from falling from the pipette tips 222 and / or from the dispense heads 328 and landing on the deck 126 or on or in one of the consumables 200. Through this the drip tray assembly 336 plays a significant role in mitigating contamination nsks and enabling automated digital PCR. The drip tray may have a removeable and replaceable consumable containing a liquid soaking absorbent material. The drip tray assembly 336 is movably coupled to the pipettor body 316 and is independently moveable with respect to both the pipettor body 316 and the pipettor assembly 320. In some embodiments, the drip tray assembly is movable via a drip tray z-motor 338. The drip tray z-motor 338 can comprise any desired motor and / or actuator including, for example, a stepper motor, a linear actuator, or the like. In some embodiments, the drip tray z- motor 338 can drive a belt which can be coupled to the drip tray assembly 336 and the movement of which belt can move the drip tray assembly 336 either in a positive z-direction or in the negative z-direction.

[0183] The drip tray z-motor 338 is communicatively coupled to the controller 300. Via this communicative coupling, the controller 300 can determine, track, and / or monitor the relative position of the drip tray assembly 336 with respect to the pipettor body 316 and / or the pipettor assembly 320, and specifically monitor whether the dnp tray is in a deployed position or in a stowed position. The controller 300 can generate one or several control signals controlling operation of the drip tray z-motor 338 to move the drip tray assembly 336, and specifically the drip tray to a desired position and / or state.

[0184] The pipettor 150 further includes one or several suction cups 340 that can be, as shown in Figure 13, coupled to the drip tray assembly 336 and / or can be a part of the drip tray assembly 336. The one or several suction cups 340 can include for example 1, 2, 3, 4, 5, 6, 8, 10, 15, 20, or any other or intermediate number of suction cups. The suction cups 340 can, in some embodiments, be circular and can have a diameter of between 5 mm and 15 mm. The one or several suction cups 340 can be fluidly connected to the pump 332 so that, when the one or several suction cups 340 engage with a surface of an object, the pump 332 can create a vacuum within the suction cups 340. This vacuum can securely couple the object to the suction cups 340 such that the object can be moved around the deck 126 by the pipettor 150. In some embodiments, for example, the pipettor 150 can move the PCR chip 234 from the PCR cartridge holder 160 to the chip tray 144. and / or can move the PCR chip lid 236 from the PCR cartridge lid holder 162 to the chip tray 144 to be positioned on top of the PCR chip 234. In some embodiments, and upon completion of thermocycling and imaging by the reader module 124, the pipettor 150 can utilize suction cups 340 to retrieve the PCR chip 234 and / or the PCR chip lid 236 from the chip tray 144. The size of the suction cups and applied vacuum is selected such that the total vacuum force is greater than the weight of the consumable it has to pick-up and transfer from one location to another. As previously discussed, the pump 332 is communicatively coupled to the controller 300. Accordingly, the controller 300 can control the pump 332 to control the generation of vacuum in the suction cups 340.

[0185] With reference now to Figure 14, a perspective view of one embodiment of one embodiment of a thermocycler 306 and a PCR chip 234. The thermocycler 306 can be configured to thermocycler the PCR chip 234, and specifically, to selectively and cyclically heat and cool the PCR chip 234.

[0186] The thermocycler 306 includes a heating / cooling plate 402, a thermal element 404. a frame 406, one or more sets of heat exchange fins 408, and / or one or more cooling fans 410. The heating / cooling plate 402 can be configured to physically engage and / or couple with the PCR chip 234 to thereby transfer heat from the heating / cooling plate 402 to the PCR chip 234. In some embodiments, for example, a bottom surface 403 of the heating / cooling plate 402 can be configured to engage with a surface, such as a top surface 269 of the PCR chip 234. In some embodiments, this engagement can include pressing the bottom surface 403 of the heating / cooling plate 402 onto the top surface 269 of the PCR chip 269. In embodiments in which both the bottom surface 403 of the heating / cooling plate 403 and the top surface 269 of the PCR chip 234 are flat and / or have corresponding contours, the pressing of the bottom surface 403 of the heating / cooling plate 402 onto the top surface 269 of the PCR chip 234 bring the bottom surface 403 of the heating / cooling plate 403 into consistent and intimate contact with the top surface 269 of the PCR chip 234, thereby enabling heat transfer, and more specifically enabling consistent heat transfer from the heating / cooling plate 402 to the PCR chip 234.

[0187] In some thermocyclers 306, the heating / cooling plate 402 can comprise a block of thermally conductive material. The heating / cooling plate 402 can, in some embodiments, comprise solid block of metal such as a solid block of aluminum.

[0188] In some embodiments, the thermal element 404 can comprise one or several elements having a controllable temperature. In some embodiments, the thermal element 404 can be configured generate and / or dissipate thermal energy to thereby heat or cool the heating / cooling plate 402. The thermal element 404 can, in some embodiments, one or more Peltier device (thermoelectric coolers). In the embodiment depicted in Figure 14, the thermal element 404 comprises four Peltier devices. In the embodiment depicted in Figure 14, the four thermal elements 404 decrease temperature variability across the heating / cooling plate 402, thereby facilitating consistent heating / cooling of the PCR chip 234.

[0189] In some embodiments, the thermal elements 404 can be held in a position relative to the heating / cooling plate 404 via a frame 406. In some embodiments, the frame 406 can be a part of the heating / cooling plate 404 and / or can be attached to the heating / cooling plate 404. The frame 406 can, in some embodiments, comprise a thermally conductive material such as metal including, for example, brass, copper bronze, gold, silver, aluminum, iron, steel, or the like.

[0190] The thermocycler 306 can include a cooling module 407. The cooling module 407 can be configured to dissipate heat generated by the thermal elements 404 to thereby cool the heating / cooling plate 402 and the thereto thermally coupled PCR chip 234. As depicted in Figure 14, the cooling module 407 includes the heat exchange fins 408 and one or more fans 410. As further seen in Figure 14, in some embodiments, the heat exchange fins 408 can be thermally coupled to the thermal elements 404 via one or several heat pipes 412, which can conduct heat from the thermal elements 404 to the heat exchange fins 408.

[0191] With reference now to Figure 15, a perspective view of another embodiment, and specifically of a dual vapor chamber embodiment of a thermocycler 306 is shown. As seen, the thermocycler 306 includes a plurality of vapor chambers, and specifically includes dual vapor chambers. As seen, the thermocycler 306 includes a first vapor chamber 502 and a second vapor chamber 504. Details of the first vapor chamber 502 and / or second vapor chamber 504 are discussed below with respect to Figures 16 and 17. The thermocycler 306 further includes one or several thermal elements 404. which can be one or several Peltier devices. In some embodiments, the one or several thermal elements can be coupled to the first vapor chamber 502 and / or the second vapor chamber 504 via one or several conductive elements 510 which can be one or several graphite pads. These one or several conductive elements 510 can include a top conductive element 510-A coupling the one or several thermal elements 404 to the first vapor chamber 502 and a bottom conductive element 510-B coupling the one or several thermal elements 404 to the second vapor chamber 504.

[0192] Ther thermal cycler includes the cooling module 407 that can include the heat sink 512 that can include one or more sets of heat exchange fins 408, and / or one or more cooling fans 410. In the embodiment depicted in Figure 15, a single cooling fan 410 is positioned above the heat sink 512 and oriented to move air through the heat sink 512 and vertically above the cooling fan 410. As depicted in Figure 15, the one or more cooling fans 410 can be coupled to the heat sink 512 via fan shroud 514.

[0193] With reference now to Figure 16, a depiction of another embodiment of a thermocycler 306 is shown. The embodiment of the thermocycler in Figure 16 includes a plurality of vapor chambers, and specifically includes dual vapor chambers. Specifically, the thermocycler includes the first vapor chamber 502.

[0194] Figure 17 depicts one embodiment of a vapor chamber 600. In some embodiments, the vapor chamber 600 can be first vapor chamber 502 and / or the second vapor chamber 504. The vapor chamber 600 can comprise an envelope 602 comprising walls having external surfaces 604 and internal surfaces 606. As depicted in Figure 17, the internal surfaces 606 of the envelope 602 define an internal volume 608.

[0195] The envelope 602 can comprise a variety of shapes and sizes and can be made from a variety of materials. In some embodiments, the envelope 602 can comprise a thermally conductive material such as a metal. The metal can comprise, for example, aluminum, brass, bronze, copper, steel, iron, silver, or the like. In some embodiments, the envelope can comprise a non-metallic material having a coefficient of thermal conductivity similar to a metal. In some embodiments, the envelope 602 can comprise a non-metallic material having a coefficient of thermal conductivity that is approximately equal to the thermal coefficient of one of the above-identified metals and / or that is equal to a value approximately in the range defined by the above-identified metals. As used herein, approximately is defined as the based value with which ‘"approximately” is associated + / - 10%, + / - 20%, and / or + / - 25% of that base value.

[0196] The envelope 602 can comprise a top 610 and a bottom 612. In some embodiments, the interior surfaces 606 of the top 610 comprise first surface, and in some embodiments, the interior surfaces 606 of the bottom 612 of the envelope 602 comprise a second surface. In some embodiments, the first surface can comprise one of an evaporation surface or a condensation surface, and the second surface can comprise the other of the evaporation surface or the condensation surface.

[0197] In the embodiment depicted in Figure 17, the first surface comprises an evaporation surface. In some embodiments, heat can be configured to enter into the top 610 and to the evaporation surface. In such an embodiment, liquid, also referred to herein as “fluid” and / or “working fluid” contained within the envelope 602 absorbs the heat and evaporates at the evaporation surface. The evaporated liquid spreads through the vapor chamber 600, and specifically through the envelope 602 of the vapor chamber 600, and condenses on a condensation surface located at the second surface at the bottom 612 of the envelope 602.

[0198] A wick 614 can extend around at least a portion of the interior volume 608 defined by the envelope 602. The wick 614 can, in some embodiments, comprise a mesh member or capillary channels or microchannels.

[0199] The wick 614 can, in some embodiments, extend across all or portions of the first surface and / or across all or portions of the second surface. Thus, in some embodiments, the wick can extend across all or portions of the evaporation surface and / or around all or portions of the condensation surface. In some embodiments, the wick 614 can be configured to collect condensed liquid from one of the first surface or the second surface and transport the condensed liquid to the other of the first surface or the second surface. In some embodiments, the wick 614 can be configured to capture condensed fluid and transport the condensed fluid from the condensation surface back to the evaporation surface. Once the fluid is returned to the evaporation surface by the wick 614, and assuming the continued presence of heat, the fluid can again be evaporated and spread throughout the interior volume 608. Via the evaporation and condensation of the fluid, heat is effectively and efficiently moved throughout the interior volume 608 of the envelope 602 of the vapor chamber 600 and heat is effectively and efficiently spread to all portions of the envelope 602 and through the vapor chamber 600. In some embodiments, this efficient and effective spread of heat throughout the vapor chamber 600 can increase temperature consistency across the vapor chamber 600, which can surprisingly allow for use of a smaller number of thermal elements 404 to control a temperature of the vapor chamber 600. This smaller number of thermal elements 404 can use less energy7for thermo-cycling the PCR chip 234, while maintaining the same, or better temperature consistency across the vapor chamber 600 as compared to the temperature consistency across a solid heating / cooling plate 404.

[0200] In Figure 17, the fluid is represented by arrows 613, and specifically by arrow 613-A representing evaporating fluid and 613-B representing condensed fluid.

[0201] In some embodiments, the top 610 and the bottom 612, and specifically the first surface and the second surface can be connected by one or several columns 616. In some embodiments, these one or several columns can be configured to support the envelope 602 and / or to prevent the collapsing and / or compression of the internal volume 608. In some embodiments, the one or several columns 616 can be further configured to conduct heat between the first surface and the second surface. In some embodiments, one or more of the columns 616 can comprise a copper column. In some embodiments, the first vapor chamber 502 can have a first orientation as indicated by arrow 501 in Figure 16. In this first orientation, a top 610 of the first vapor chamber 502 can thermally and / or mechanically couple to the thermal element 404. In some embodiments, this thermal and / or mechanical coupling of the top 610 of the first vapor chamber to the thermal element 404 can be achieved by the consistent and / or intimate contact of the top 610 of the first vapor chamber 502 with the thermal element 404. This consistent and / or intimate contact can be achieved by pressing the top 610 of the first vapor chamber 502 against the thermal element 404.

[0202] In some embodiments, and when in the first orientation 501 indicated in Figure 16, the bottom 612 of the first vapor chamber 502 can be thermally and / or mechanically coupled to the PCR chip 234, and specifically can be thermally and / or mechanically coupled to a top surface 269 of the PCR chip 234. In some embodiments, this thermal and / or mechanical coupling of the bottom 612 of the first vapor chamber 502 to the PCR chip 234 can be achieved by the consistent and / or intimate contact of the bottom 612 with the top 239 of the PCR chip 234. This consistent and / or intimate contact can be achieved by pressing the bottom 612 of the first vapor chamber 502 onto the top 239 of the PCR chip 234.

[0203] In some embodiments, the thermocycler 302 can further include the second vapor chamber 504. The second vapor chamber 504 can include the same or different features as the first vapor chamber 502. In the embodiment depicted in Figure 16, the first vapor chamber 502 and the second vapor chamber 504 have the same features, but the first vapor chamber 502 has the first orientation 501 and the second vapor chamber 504 has a second orientation which is opposite to the first orientation. Thus, as seen in Figure 16, the different orientations of the first and second vapor chambers 502, 504 results in the tops 610 of the first vapor chamber 502 and the second vapor chamber 504 being relatively closer to each other than are the bottoms 612 of the first vapor chamber 502 and the second vapor chamber 504.

[0204] Thus, in some embodiments, the thermocycler 302 can include the second vapor chamber 504 which can include a second top 610 and an opposing second bottom 612. The second vapor chamber can have a second orientation opposite to the first orientation of the first vapor chamber 502. In some embodiments, and as shown in Figure 16, the second top 610 of the second vapor chamber 604 is thermally and / or mechanically coupled to the thermal element 404 such that the thermal element is located between the top 610 of the first vapor chamber 502 and the second top 610 of the second vapor chamber 504. Thus, in some embodiments, the thermal element 404 is coupled to the top 610 of each of the first vapor chamber 502 and the second vapor chamber 504.

[0205] In some embodiments, this thermal and / or mechanical coupling of the top 610 of the second vapor chamber 504 to the thermal element 404 can be achieved by the consistent and / or intimate contact of the top 610 with the thermal element 404. This consistent and / or intimate contact can be achieved by pressing the top 610 of the second vapor chamber 504 onto thermal element 404, and as depicted in Figure 16, onto an opposite side of the thermal element 404 onto which the top 610 of the first vapor chamber 502 is pressed.

[0206] In some embodiments, the thermocycler can include a cooling module 407 that can include one or more sets of heat exchange fins 408, and / or one or more cooling fans 410. In some embodiments, and as depicted in Figure 16, the heat exchange fins 408. also referred to herein as heat exchanger fins 408 are coupled to the bottom 612 of the second vapor chamber 504, or in other words, to the second bottom 612. In some embodiments, this can include the coupling of a fin bottom 620 to the bottom 612 of the second vapor chamber 504.

[0207] In some embodiments, the heat exchanger fins 408 can comprises an array of fins 622, each of which fins 622 can comprise a planar member. In some embodiments, the fins 622, or in other words, the planar members forming the array of fins can be parallel. Thus, in some embodiments, each of the fins of the heat exchanger fins 408 can be parallel to the other fins of the heat exchanger fins 408.

[0208] In some embodiments, and as depicted in Figure 16, the heat exchanger fins 408 can be coupled to the second vapor chamber 504, and specifically to the bottom 612 of the second vapor chamber 504. The fins 622 in the heat exchanger fins 408 can extend away from the bottom 612 of the second vapor chamber 504. In some embodiments, each of the fins 622 of the heat exchanger fins 408 can extend in a first direction perpendicularly away from the bottom 612 of the second vapor chamber 504, which first direction can be opposite to the arrow 501 indicating the first orientation.

[0209] As further depicted in Figure 16, the cooling module 407 includes the cooling fan 410. The cooling fan 410 can comprise an electric fan that can be, for example, configured to move air across the heat exchanger fins 408. In some embodiments, this can include, for example, blowing and / or sucking air across the heat exchanger fins 408. In some embodiments, the fan 410 can be positioned at and / or adjacent to a fin top 624 of the heat exchanger fins 408. In some embodiments, the fan 410 can be oriented to move air in a direction parallel to the fins 622 and / or in a direction parallel to the direction indicated by arrow 501. In some embodiments, the fan 410 can be oriented to move air in a direction perpendicular to the fin bottom 620 and / or perpendicular to the bottom 612 of the second vapor chamber 504.

[0210] With reference now to Figure 18, a top view of one embodiment of a first vapor chamber 502 is shown. As seen, the first vapor chamber 502 is coupled to the thermal element 404, and specifically, the thermal element 404 is coupled to the top 610 of the first vapor chamber 502. The thermal element 404, which can be a Peltier device, also referred to herein as a thermoelectric cooling module, can receive power via a power connector 630 which can be one or several wires, leads, or the like.

[0211] In some embodiments, this single thermal element can have a power draw of, for example, less than approximately 200 Watts, less than approximately 150 Watts, less than approximately 120 Watts, less than approximately 100 Watts, less than approximately 80 Watts, of approximately 120 Watts, of approximately 80 Watts, or any other or intermediate power draw.

[0212] With reference now to Figure 19, a perspective view of one embodiment of the second vapor chamber 504 is shown. In some embodiments, a coupling pad 652 can be coupled to the top 610 of the second vapor chamber 504 and / or to the top of the first vapor chamber 502. In some embodiments, the coupling pad 652 can facilitate the physical and / or thermal coupling between the thermal element 404 and the one of the first vapor chamber 502 or the second vapor chamber 504 to which the coupling pad 652 is coupled. In some embodiments the coupling pad 652 can be deformable to facilitate the coupling of the thermal element 4040 with the respective one of the first vapor chamber 502 or the second vapor chamber 504 to which the coupling pad 652 is coupled.

[0213] With reference now to Figure 20, a perspective view of one embodiment of the thermocycler 306 is shown. The thermocycler 306 includes the first vapor chamber 502 connected to the second vapor chamber 504. Although not visible in Figure 20, the thermal element 404 is sandwiched between the first vapor chamber 502 and the second vapor chamber 504, and specifically is sandwiched between the tops 610 of the first vapor chamber 502 and the second vapor chamber 504. The bottom 612 of the second vapor chamber is coupled to the heat exchange fins 408, which comprise a plurality of planar fins 622. which planar fins are parallel and extend perpendicularly away from the bottom 612 of the second vapor chamber 504. In some embodiments, one, some, or all of the first vapor chamber 502, the second vapor chamber 504, and the heat exchanger fins 408 can comprise bronze, brass, copper, aluminum, steel, iron, gold, silver, or any other thermally conductive metal. In some embodiments, one, some, or all of the first vapor chamber 502, the second vapor chamber 504, and the heat exchanger fins 408 can comprise a coating and / or layer of bronze, brass, copper, aluminum, steel, iron, gold, silver, or any other thermally conductive metal.

[0214] With reference now to Figure 21, an embodiment of the thermocycler 306 is shown. As seen, in this embodiment, the fan 410 is positioned at a top 624 of the heat exchanger fins 408. The fan 410 is positioned and oriented such that the fan 410 can blow or such air through the fins 622 of the heat exchanger fins 408 in a direction parallel to the fins 622 and / or perpendicular to the fin bottom 620 and / or perpendicular to the bottom 612 of the second vapor chamber 504.

[0215] With reference now to Figure 22, graphs illustrating results of use of embodiments of the thermocycler disclosed herein are shown. Specifically, the graphs depicted in Figure 22 depict the performance of a vapor chamber 602 as used in a thermocycler described herein. The embodiment associated with these results includes use of dual vapor chambers 602 as depicted in Figure 16, and use of a single thermal element 404. In results, the thermal element 404 drew approximately 80 Watts of electricity.

[0216] Graph (a) depicts temperature uniformity as measured over time, or in other words, how uniform the temperature is across the vapor chamber 602 at a time after turning on the thermal element 404. As indicated in the graph, the vapor chamber 602 has temperature variability of + / - 0.5 °C. This stands in stark contrast to embodiment of the solid heating / cooling plate 402, which has + / - 4 °C temperature variability across the solid heating / cooling plate 402 when the solid heating / cooling plate 402 is being heated / cooled by four thermal elements 404.

[0217] Graph (b) shows the ramp rates of approximately 1.2 °C / s of the vapor chamber 602 utilizing a single thermal element 404 drawing approximately 80 Watts of electricity. This is a higher ramp rate than achieved with the solid heating / cooling plate 402 combined with four thermal elements 404, each drawing 80 Watts of electricity.

[0218] In contrast to present designs, which utilize four thermal elements 404, the thermocycler 302 utilizing at least one vapor chamber 602. such as shown in the embodiment depicted in Figure 16, has improved temperature uniformity, and improved ramp times. Further, this improved performance is achieved while using approximately 25% of the power used in the embodiment with the solid heating / cooling plate 402 and the four thermal elements 404. Furthen and in contrast to the thermocycler utilizing a solid heating / cooling plate 402, the embodiments of the thermocycler 302 utilizing at least one vapor chamber 602 are lighter. While the current design shows a dual vapor pressure thermocycler, other combinations where only one vapor chamber could be used in a design either on the sample side or on the heat-fin side for various other considerations too.

[0219] With reference now to Figure 23, a flowchart illustrating one embodiment of a process 700 for automated digital PCR is shown. The process 700 can be performed by all or portions of the system 100. In some embodiments, the process 700 can be performed according to instructions provided by the GUI via the display 304 as controlled by controller 300. The process 700 can include determining, generating, and / or collecting of data, values, and / or images. In some embodiments, some or all of these data, values, and / or images can be stored in one or several databases in the memory 302.

[0220] The process 700 can include a number of core steps that will be explained in greater detail below; These include performing pipetting operations with the multi-channel pipettor to transfer a portion of the sample from the sample tube to a PCR cartridge, thermocycling the sample in the PCR cartridge with the heater, and imaging the sample in the PCR cartridge with the imager. In some embodiments, performing these pipetting operations can include moving a drip tray from an undeployed position to a deployed position to prevent and droplets from falling from the pipettor 150 onto the deck 126 or onto a consumable 200. In some embodiments, the drip tray can be moved to the deployed position each time the pipettor 150 is moved above and across the deck 126. In some embodiments, the drip tray is held in the deployed position until the pipettor is at a position to aspirate or dispense.

[0221] The process 700 begins at block 702 wherein the user places one or several samples in a holder on the deck 126 of the system 100. As used herein, “sample” and “plasma” are equivalent. In some embodiments, this can include placing one or several sample tubes 206 containing a sample in the sample tube holder 151 on the deck 126 of the system 100.

[0222] In some embodiments, the sample tubes 206 are part of the sample tube system 202. Specifically, in some embodiments, the sample tube system 202 can include the sample tube rack 204 in the sample tubes 206. In some embodiments, the sample tubes 206 can be received within the sample tube rack 204, and the sample tube system 202 can be received within the sample tube holder 151.

[0223] In some embodiments, and as part of the step of block 702, the system 100 can confirm that the sample is received in the holder on the deck 126 of the system 100. In some embodiments, this can include confirming the one or several sample tubes 206 are received within the sample tube holder 151 in the deck 126. In some embodiments, this confirming can include scanning and identification feature on a sample tube 206 that is received within the sample tube holder 151 and comparing that identification feature and / or information encoded in that identification feature to information identifying a sample tube 206 that was expected to be received in the sample tube holder 151. If the information from the identification feature and / or the identification feature matches the information for the expected sample tube 206, then receipt of the expected sample tube 206 the sample tube holder 151 can be confirmed.

[0224] At block 704 the sample is lysed. In some embodiments, this can include using the pipettor 150 to pick up a pipette tip 222 from the tip box 216. The pipettor 150 can use the pipette tip 222 to aspirate plasma from the sample tube 206 and dispense that aspirated sample into the lysis / binding plate 208. In some embodiments, and after the pipettor 150 has aspirated the plasma, the drip tray can be put in the deployed position to catch any droplet falling from the pipettor 150. In some embodiments, the pipettor 150 can aspirate and transfer 1 mL of plasma from the sample tube to one of the wells of the lysis / binding plate 208. This transfer can be repeated, transferring plasma from one of the sample tubes 206 to a well of the lysis / binding plate 208 until, for example, 4 mL of plasma are transferred to that one of the wells of the lysis / binding plate 208.

[0225] The pipettor 150 can be used to transfer one or several reagents, such as, for example, an enzy me to cause lysis such as, for example, a protease such as proteinase K, from the reagent cartridge 212 to the well in the lysis / binding plate 208 containing the transferred sample. In some embodiments, the pipettor 150 can be used to mix the one or several reagents with the plasma in the well of the lysis binding plate 208 by repeatedly aspirating and dispensing solution from that well. The sample and reagents in the well of the lysis / binding plate 208 can be incubated and / or shaken for a duration of time. In some embodiments, this can include incubating the sample and reagents in the well of the lysis binding plate 208 at a temperature of 37 °C for between 10 and 20 minutes, and in some embodiments, for approximately 15 minutes. In some embodiments, the lysis / binding plate 208 can be shaken while being incubated at, for example, approximately 1500 RPM.

[0226] At block 706. the lysed sample can be bound with magnetic beads. In some embodiments, this can include the transferring of binding solution from the reagent cartridge 212 to the well of the lysis / binding plate 208 with the pipettor 150. The binding agent, which can include magnetic beads for binding with nucleic acid, can be mixed with the sampling reagents in the well of the lysis / binding plate 208. In some embodiments, the sample, reagents, and binding solution can be incubated and / or shaken for a duration of time. In some embodiments, this can include incubating the sample, reagents, and binding solution in the well of the lysis binding plate 208 at a temperature of 37 °C for between 10 and 20 minutes, and in some embodiments, for approximately 15 minutes. In some embodiments, the lysis / binding plate 208 can be shaken while being incubated at. for example, approximately 1500 RPM. In some embodiments, the steps of block 704 and 706 can be performed separately, and in some embodiments, the steps of block 704 and 706 can be combined together such that both the reagents and the binding solution are added to the well containing the plasma, and are then altogether incubated.

[0227] At step 708, the magnetic beads that are bound to nucleic acid are separated from supernatant. In some embodiments, this can include performing a preconcentration process in a pipette tip 222 and / or can include separation of the magnetic beads from supernatant via a magnetic separator 134. In some embodiments, the preconcentration process can include aspirating 1 mL of solution including sampling beads and increasing the concentration of the magnetic beads in the solution lOx while in the pipette tip 222. In some embodiments, separating the magnetic beads from supernatant via the magnetic separator 134 can include aspirating lysed sample including the magnetic beads from the well of the lysis / binding plate 208 with the pipettor 150 and transferring that to a well of the magnetic separation plate 224 which is on the magnetic separator 134. In some embodiments, the solution including the magnetic beads and bound nucleic acid that is dispensed to a well of the magnetic separation plate 224 can already be pre-concentrated in the pipette tip 222.

[0228] While in the well of the magnetic separation plate 224, a magnetic field can be applied to the solution including the magnetic beads to facilitate further concentration of the magnetic beads. While the magnetic beads are held in place by the applied magnetic field, the supernatant can be aspirated from the well of the magnetic separation plate 224. After sufficient amounts of supernatant have been aspirated from the well of the magnetic separation plate 224, one or several washes can be performed to further purify the nucleic acid bound to magnetic beads. These washes can include mixing the wash solution with the magnetic beads, applying a magnetic field to the combination of the wash solution and the magnetic beads, and while the magnetic beads are held in place by the magnetic field, aspirating the supernatant from the well of the magnetic separation plate 224. The supernatant can be disposed of in a well of the reagent cartridge 212 by the pipettor 150. These washes can be performed multiple times to achieve a desired purity of nucleic acid in the well of the magnetic separation plate 224.

[0229] At block 710, the nucleic acid is eluted from the magnetic beads. In some embodiments, this can include aspirating elution buffer from a well of the reagent cartridge 212, and transferring that elution buffer to the well of the magnetic separation plate 226. The elution buffer can be allowed to sit, mixed with the magnetic beads for a period of time during which the nucleic acid separates from the magnetic beads.

[0230] At block 712, the eluted sample can be transferred to one or several wells of the assay strip 228 to create one or several assay mixes 712. In some embodiments, this can include transferring portions of the eluted sample to different wells of the assay strip 228. each of which wells can correspond to an assay, and can contain one or several reagents and / or master mix for that assay. In some embodiments, for example, this can include a first well for a first assay such as an NIPT assay, and a second well for a second assay such as an FF assay.

[0231] In some embodiments, an additional DNA or nucleic acid quantification step can be performed at any appropriate time, for example, after the sample is eluted and prior to transferring the eluted sample to one or several wells of the assay strip 228, or any other time that may be appropriate. This quantification step quantifies the nucleic acid in the sample and / or eluted sample, and in some embodiments, the DNA in the sample and / or eluted sample. The quantification step can include aspirating or dispensing a quantification reagent, for example, from the reagent cartridge 212, into a well of the quant strip 230 with pipettor 150. In some embodiments, the quantification reagent may already be in the well of the quant strip 230. A portion of a sample or eluted sample, for example, 2 pL of the eluted sample, can be aspirated and can be dispensed into the well of the quant strip. The quant reagent and the portion of the sample and / or eluted sample can be mixed by the pipettor 150. and can then be transferred via the pipettor 150 to one of the quant wells 258 of the PCR chip 234. The PCR chip is then imaged by the imager to detect the quantity of the nucleic acid, for example, by imaging the amount of fluorescence. In some embodiments, a pre-stored calibration value can be used to quantitate the nucleic acid in the quant wells 258. The quantification information can be used in determining the amounts of samples necessary for performing certain steps of an assay or for understanding results generated from a volume of sample and / or eluted sample.

[0232] In some embodiments, and before transferring the eluted sample to the assay strip 228, a preamplification protocol can be performed to increase the quantity’ of nucleic acid in the sample. This can include transferring a buffer for preamplification from the reagent cartridge 212 to the pre-amp strip 232 with the pipettor 150. strip 232. An amount of eluted sample can be aspirated by the pipettor 150 from the well of the magnetic separation plate 226. and can be transferred to the well of the pre-amp strip 232 containing the preamp-PCR buffer. The preamp-PCR buffer can be mixed with the eluted sampled in the well of the pre-amp strip 232 via repeated aspiration and dispensing by the pipettor 150.

[0233] A layer of oil, such as mineral oil can be created over the mixture of the preamp-PCR buffer and the eluted sample in the well of the pre-amp strip 232. The layer can be created by transferring oil from the reagent cartridge 212 with the pipettor 150 to the well of the pre-amp strip. After this layer of oil has been created, the mixture of the sample and the pre-amp solution can be thermocycled by the preamp thermocycler 130.

[0234] At block 714 assay mixes are transferred from the assay strip 238 to the PCR chip 234. In some embodiments, this transfer can be performed by the pipettor 150. In embodiments in which the PCR chip comprises a plurality of microwells, transferring the assay mixes to the PCR chip 234 can include aspirating a portion of assay mix from the assay strip 238 and dispensing that portion of assay mix into a plurality of micro-wells in one of the regions 252, 255, 256 of the PCR chip 234. This can be repeated until all of the assay mix or assay mixes have been transferred to micro-wells on the PCR chip 234.

[0235] Alternatively, the PCR chip 234 is configured for droplets, transferring the assay mixes to the PCR chip 234 can include aspirating a portion of the assay mix from the assay strip 238 with the pipettor and dispensing a portion of the assay mix into a microfluidic device configured to generate micro-droplets, which micro-droplets are then loaded into the PCR chip 234. This can be repeated until all the assay mix or assay mixes have been transferred to regions 252. 255, 256 of the PCR chip 234. At block 716, and in the event that the PCR chip 234 comprises a plurality of micro-wells, the PCR chip lid 236 is retrieved with the pipettor 150 and secured to the PCR chip 234. In some embodiments, the PCR chip lid 236 can be retrieved with the suction cups 340 of the pipettor 150 from the PCR chip lid holder 162, and can be placed on the PCR chip 234 in the chip tray 144. In some embodiments, the pipettor can press the PCR chip lid 236 onto the PCR chip 234 with sufficient force to couple the PCR chip lid 236 to the PCR chip 234. In some embodiments, the PCR chip lid 236 can be sealed to the PCR chip 234 and the microwells on the PCR chip 234 can be sealed via the application of heat to the PCR chip lid 236 and the PCR chip 234 by the thermocycler 306. In some embodiments, sealing the PCR chip lid 236 to the PCR chip 234 can include sliding the chip tray 144 into the reader module 124 and then bringing the thermocycler 306 into contact with the PCR chip lid 236.

[0236] At block 718. the PCR chip 234 is moved to the thermocycler 306 and the PCR chip 234 and partitions on the PCR chip 234 are thermocycled. At block 720 the PCR chip 234, and specifically, the partitions of the PCR chip are imaged by the imager 308. In some embodiments, this can include illuminating the PCR chip 234 with excitation energy from the excitation source 310, and capturing one or several images of the PCR chip 234 with the image capture feature 312, which image capture feature can comprise a camera in some embodiments, the PCR chip 234 can be imaged with six channels of excitation energy, and with corresponding images. In some embodiments, a number of images can be generated per PCR chip 234 including, for example, between 5 and 250 images, between 20 and 100 images, approximately 50 images, or any other or intermediate number of images.

[0237] This description should not be interpreted as implying any particular order or arrangement among or between various steps or elements except when the order of individual steps or arrangement of elements is explicitly described. Different arrangements of the components depicted in the drawings or described above, as well as components and steps not shown or described are possible. Similarly, some features and sub-combinations are useful and may be employed without reference to other features and sub-combinations. Embodiments of the invention have been described for illustrative and not restrictive purposes, and alternative embodiments will become apparent to readers of this patent. Accordingly, the present invention is not limited to the embodiments described above or depicted in the drawings, and various embodiments and modifications may be made without departing from the scope of the claims below.

Claims

WHAT IS CLAIMED IS:

1. A method of performing automated digital Polymerase Chain Reaction (PCR), the method comprising: receiving a sample in a PCR cartridge; thermocy cling the sample in the PCR cartridge with a thermocycler of an automated PCR system, the thermocycler comprising: a thermal element; and a first vapor chamber thermally coupled to the thermal element and configured to thermally couple to the PCR cartridge to thermocycle the sample; and imaging the sample in the PCR cartridge with an imager of the automated PCR system2. The method of claim 1. wherein the first vapor chamber comprises: an envelope comprising interior surfaces defining an interior volume; a wick extending around at least a portion of the interior volume; and working liquid contained within the interior volume.

3. The method of claim 2. wherein the first vapor chamber comprises a top and an opposing bottom, wherein the interior surfaces comprise an evaporation surface at the top and a condensing surface at the bottom, wherein a first portion of the wick extends across the evaporation surface and a second portion of the wick extends across the condensing surface, and wherein the wick is configured to collect condensed liquid from the condensing surface and transport the condensed liquid to the evaporation surface.

4. The method of claim 2, wherein the first vapor chamber comprises a top and an opposing bottom, wherein the interior surfaces comprise a first surface at the top and a second surface at the bottom, wherein a first portion of the wick extends across the first surface and a second portion of the wick extends across the second surface.

5. The method of claim 4. wherein the wick is configured to collect condensed liquid from one of: the first surface; or the second surface, and wherein the wick is configured to transport the collected condensed liquid to the other one of: the first surface; or the second surface.

6. The method of any of claims 4 or 5, wherein the wick comprises a mesh wick, and wherein the first surface and the second surface are connected via at least one column.

7. The method of claim 6, wherein the at least one column comprises a copper column.

8. The method of any of claims 3 through 5, wherein the first vapor chamber has a first orientation with the top of the first vapor chamber coupling to the thermal element.

9. The method of claim 8, the thermocycler further comprising a second vapor chamber comprising a second top and an opposing second bottom, the second vapor chamber having a second orientation opposite to the first orientation of the first vapor chamber, and wherein the second top of the second vapor chamber is coupled to the thermal element such that the thermal element is located between the top of the first vapor chamber and the second top of the second vapor chamber.

10. The method of claim 9. the thermocycler further comprising: heat exchanger fins coupled to the second bottom of the second vapor chamber; and a fan configured to blow air across the heat exchanger fins.1 1 . The method of claim 10, wherein the heat exchanger fins comprise a fin bottom coupled to the second bottom of the second vapor chamber, and wherein the fins extend in a first direction perpendicularly away from the second bottom of the second vapor chamber.

12. The method of claim 11, wherein the fan is adjacent to a fin top of the heat exchanger fins, and wherein the fan is oriented to blow air from the fin top towards the fin bottom of the heat exchanger fins.

13. A system for performing automated Polymerase Chain Reaction (PCR), the system comprising: a thermocycler configured to thermocycle samples in a PCR cartridge, the thermocycler comprising:a thermal element; and a first vapor chamber thermally coupled to the thermal element and configured to thermally couple to the PCR cartridge during thermocycling of the PCR cartridge; an imager; and a processor communicatively coupled with each of the thermocycler, and the imager, wherein the processor is configured to control operation of each of the thermocycler, and the imager to perform digital PCR, wherein the processor is configured to: thermocycle the sample in the PCR cartridge with the thermocycler; and image the sample in the PCR cartridge with the imager.

14. The system of claim 13, wherein the first vapor chamber comprises: an envelope comprising interior surfaces defining an interior volume; a wick extending around at least a portion of the interior volume; and working liquid contained within the interior volume.

15. The system of claim 14, wherein the first vapor chamber comprises a top and an opposing bottom, wherein the interior surfaces comprise an evaporation surface at the top and a condensing surface at the bottom, wherein a first portion of the wick extends across the evaporation surface and a second portion of the wick extends across the condensing surface, and wherein the wick is configured to collect condensed liquid from the condensing surface and transport the condensed liquid to the evaporation surface.

16. The system of claim 14, wherein the first vapor chamber comprises a top and an opposing bottom, wherein the interior surfaces comprise a first surface at the top and a second surface at the bottom, wherein a first portion of the wick extends across the first surface and a second portion of the wick extends across the second surface.

17. The system of claim 16, wherein the wick is configured to collect condensed liquid from one of: the first surface; or the second surface, and wherein the wick is configured to transport the collected condensed liquid to the other one of: the first surface; or the second surface.

18. The system of any of claims 16 or 17, wherein the wick comprises a mesh wick, and wherein the first surface and the second surface are connected via at least one column.

19. The system of claim 18, wherein the at least one column comprises a copper column.

20. The system of any of claim 15 through 17, wherein the first vapor chamber has a first orientation with the top of the first vapor chamber coupling to the thermal element.

21. The system of claim 20, the thermocycler further comprising a second vapor chamber comprising a second top and an opposing second bottom, the second vapor chamber having a second orientation opposite to the first orientation of the first vapor chamber, and wherein the second top of the second vapor chamber is coupled to the thermal element such that the thermal element is located between the top of the first vapor chamber and the second top of the second vapor chamber.

22. The system of claim 21, the thermocycler further comprising: heat exchanger fins coupled to the second bottom of the second vapor chamber; and a fan configured to blow air across the heat exchanger fins.

23. The system of claim 22, wherein the heat exchanger fins comprise a fin bottom coupled to the second bottom of the second vapor chamber, and wherein the fins extend in a first direction perpendicularly away from the second bottom of the second vapor chamber.

24. The system of claim 23, wherein the fan is adjacent to a fin top of the heat exchanger fins, and wherein the fan is oriented to blow air from the fin top towards the fin bottom of the heat exchanger fins.

25. The system of claim 22, wherein the heat exchanger fins comprises an array of planar members, wherein each of the planar members comprises a fin of the heat exchanger fins, and wherein the planar members in the array of planar members are parallel.

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