JP2005533652A - Microfluidic size exclusion device, system, and method - Google Patents

Abstract

Microfluidic devices, assemblies and systems are provided as well as methods for manipulating micro-sized samples of fluids. An exemplary embodiment of the microfluidic device (498) includes a filter frit material (412) disposed in the column (406). The filter frit material (412) includes a chamber (413) that holds a gel filtration material (418). The microfluidic device (498) includes a substrate (400), an input opening (402), a first channel (404), a second channel (408), a discharge opening (410), and first and second Covers (414, 416) are provided. A microfluidic device having a plurality of specific processing features is also provided.

Description

(Citation of related application)
No. 10 / 336,274, No. 10 / 336,330, and No. 10 / 336,706 (all filed Jan. 3, 2003); 403,640 and 10 / 403,652 (both filed on March 31, 2003); US Provisional Patent Applications 60 / 398,851 and 60 / 398,946 (both July 2002) Claims from US Provisional Patent Application No. 60 / 399,548 (filed July 30, 2002). All applications cited herein are hereby incorporated by reference in their entirety.

(Field)
The present application relates to microfluidic devices, systems comprising such devices, and methods of using such devices and systems. More specifically, the present invention relates to devices that manipulate, process, or otherwise modify the micro-sized amounts of fluids and fluid samples.

(background)
Microfluidic devices are useful for manipulating fluid samples. Microfluidic devices, systems using them, systems for processing them, and manipulating fluids that are fast, reliable, consumable and can be used to process multiple samples simultaneously There continues to be a need for ways to do this.

  According to various embodiments, a microfluidic device is provided, the microfluidic device comprising a substrate, a first channel, a second channel, a column connecting the first channel and the second channel, and in the column With a filter frit material. The substrate can have first and second opposing surfaces and thickness. The first channel may be formed in the first surface and may have a first depth extending in a direction perpendicular to the first surface and toward the second surface. The first depth is equal to or less than the thickness of the substrate. The second channel may be formed in the second surface and may have a second depth extending in a direction perpendicular to the second surface and toward the first surface. The second depth is equal to or less than the thickness of the substrate. The column can have a height that extends from the first surface to the second surface. The column may have a constant cross-sectional area and / or a constant diameter parallel to the first surface and along a plane that exists from the first surface to the second surface.

  In accordance with various embodiments, an embedded gel filtration frit is provided, the embedded gel filtration frit comprising a body comprising a form-stable filter frit material, a chamber formed in the body, and disposed in the chamber A gel filtration material is provided.

  According to various embodiments, a microfluidic device is provided, the microfluidic device comprising a substrate, a first channel, a second channel, fluid communication between the first channel and the second channel, and It comprises a flow-restricted particulate material that is stacked or packed in this fluid communication. According to such an embodiment, the substrate can have a first surface, a second surface opposite the first surface, and a thickness. The first channel can be formed in the substrate and can extend in the first direction. The first channel may have a first cross-sectional area defined by at least a first minimum dimension and a first depth, the first depth being perpendicular to the first surface. Extending in a direction and toward the second surface. This second channel may be formed in the substrate and may extend in the second direction. The second channel may have a second cross-sectional area defined by at least a second minimum dimension and a second depth, the second depth being perpendicular along the first surface. Extending in this direction and towards this second surface. The fluid communication may be formed in the substrate between the first channel and the second channel and may have a third cross-sectional area defined by at least a third minimum dimension. Here, the third cross-sectional area is smaller than the first cross-sectional area. The flow restricting material may be placed in the first channel, in fluid communication, or in both the first channel and fluid communication. The flow restricting material may include gel filtration particles, wherein at least 10% by weight of the flow restricting particles include flow restricting particles having an average particle size that is less than the third smallest dimension.

  In accordance with various embodiments, a microfluidic device is provided, the microfluidic device comprising a substrate, a first channel formed in the substrate, and a first chamber formed in the substrate. The first chamber has a teardrop-shaped cross-sectional area when depth and a cross-section perpendicular to this depth. The first chamber may have a substantially circular first end and a narrower and opposite second end. These ends collectively define a teardrop shaped cross section. The cross section of the first chamber may be constant along the depth of the first chamber. The second end of the first chamber may be in fluid communication with its first channel.

  In accordance with various embodiments, a microfluidic device is provided, the microfluidic device formed on a substrate having a first surface, a second surface opposite the first surface, and a thickness, and the substrate. A plurality of parallel paths, wherein each of the paths comprises an input opening, an exhaust opening, and at least one processing chamber positioned between the input opening and the exhaust opening, wherein the input opening in each path The at least one processing chamber and the discharge opening are arranged linearly. Each of the plurality of parallel paths may comprise at least one valve that operates to provide fluid communication between the at least one processing chamber and at least one of the input and output openings. Can be done. Each of the plurality of paths may comprise at least one valve, the valve having a first deformable material having a first elasticity, a second having a second elasticity different from the first elasticity. A deformable material and an adhesive material may be provided.

  In accordance with various embodiments, a sample processing system is provided that includes a microfluidic device, a platen, a drive unit, and a control unit as described herein. Here, the platen includes a microfluidic device holder that holds the microfluidic device. The microfluidic device can have a first surface, a second surface opposite the first surface, and a substrate having a thickness, and a plurality of parallel paths formed in the substrate. Each includes an input opening, an output opening, and at least one processing chamber between and in fluid communication with the input and output openings. The platen can have a rotation axis, and the holder can be spaced from the rotation axis and is disposed off-center with respect to the rotation axis. The drive unit can rotate the platen about its axis of rotation, and the control unit can control the drive unit.

  In accordance with various embodiments, a method of making a microfluidic device is provided, the microfluidic device being formed in a substrate, an input opening formed in the substrate, formed in the substrate, and in fluid communication with the input opening. A first channel, a second channel formed in the substrate, and fluid communication between the first channel and the second channel. The method includes introducing a flow restricting material through the input opening into a first channel, and applying a centripetal force to the microfluidic device to cause the flow restricting material to be in fluid communication with the first channel. Filling in the channel may include the step of preventing a substantial portion of the flow restricting material from moving through this fluid communication to the second channel.

  According to various embodiments, a microfluidic device is provided that includes a substrate, a first recess formed in the substrate, a second recess formed in the substrate, and a first recess and a second. An intermediate wall sandwiched between the recesses, wherein the intermediate wall portion is formed from a deformable material having a first elasticity. An elastically deformable cover layer is also provided, the cover layer covering the first recess, and the particulate flow restricting material can be disposed in the first recess. The elastically deformable cover layer may have a second elasticity that is less than the first elasticity. Here, this elastically deformable covered layer contacts the intermediate wall when the intermediate wall is in an undeformed state, where the elastically deformable cover layer is in a state where the intermediate wall is in a deformed state. In some cases, it does not contact the intermediate wall, thereby forming a fluid communication between the first recess and the second recess. This fluid communication between the first and second recesses can be designed or formed as a flow restricting factor, as described herein.

  The teachings herein may be better understood with reference to the accompanying drawings and description thereof. Modifications recognized by those skilled in the art are considered part of the teachings of the present invention.

  Various other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the devices, systems and methods described herein, and from the following detailed description. The specification and examples are to be regarded as illustrative only and the true scope and spirit of the invention is intended to encompass various other embodiments.

(Detailed description of specific embodiments)
FIG. 1 is a top view of a microfluidic device 98 according to various embodiments, which includes a substrate 100, an input opening 102, an exhaust opening 110, a first channel 104, a second channel 108, a first A chamber 106 interconnecting the channel 104 and the second channel 108 and a filter frit material 112 disposed in the chamber 106 are provided. The chamber 106 can be in the form of a column, eg, a vertical cylindrical column, as shown.

  FIG. 2 is a side cross-sectional view of the microfluidic device 98 of FIG. 1 taken along line 2-2 of FIG. As shown in FIGS. 1 and 2, the covers 114, 116, and 118 are provided in contact with the substrate 100. The cover 114 covers the bottom of the substrate 100 and provides, in part, an inner surface 115 that can define the channel 104, as shown in FIG. A fluid sample introduced into the input opening 102 passes from the input opening 102 to the first channel 104, through the first channel 104 to the chamber 106, and through the filter frit material 112 in the chamber 106 to the second channel 108. , And from the second channel 108 to the discharge opening 110. The first channel 104 can be loaded with a gel filtration material (not shown), eg, an ion exchange gel filtration material.

  The input opening 102 can be designed as an inlet port, a hole through the layer, an opening, or any other profile that provides an entrance to a channel or chamber in fluid communication. The drain opening 110 may be designed as a port, opening, hole through the layer, or any other profile that provides an exit from a channel or chamber in fluid communication. The input opening 102 and / or the discharge opening 110 may be covered or partially covered by a brittle or pierceable material cover 116, 118. The cover can be in the form of a tape, film, sheet, membrane, or a combination thereof. The cover 114 at the bottom of the device (shown) can be tape, film, sheet, membrane, or a combination thereof. Any of the covers 114, 116, and 118 can be in the form of a second substrate that is affixed, secured, glued, or otherwise connected to the substrate 100. The first channel 104, the second channel 108, the channel 106, or combinations thereof may be pre-loaded with reagents, reactants, or buffers known in the art before each cover is applied to the substrate 100. Can be filled. Thus, the first channel 104, the second channel 108, the chamber 106, or a combination thereof can be loaded through the input opening.

  FIG. 3 is a top view of a microfluidic device 498 that includes a filter frit material 412 having a shape that complements the shape of the column 406 on which the filter frit material 412 is disposed. The filter frit material 412 can include a chamber 413 that holds a gel filtration material 418. FIG. 4 is a side view of the microfluidic device 498 shown in FIG. In the embodiment shown in FIGS. 3 and 4, the device includes a substrate 400, an input opening 402, a first channel 404, a chamber 406 for receiving the filter frit material 412, a second channel 408, and a discharge opening 410. Is further provided. The device 498 shown in FIGS. 3 and 4 may also include a first cover 414 and a second cover 416. The filter frit material 412 may have an outer shape that is complementary to the inner shape of the chamber 406.

  FIGS. 5 and 6 illustrate an embodiment of a microfluidic device 700 comprising a filter frit material 712 having a shape that complements a substrate 701 and a chamber 713. The opening 720 of the filter frit material 712 faces the input opening 702 formed in the substrate 701. The filter frit material 712 further includes a closed end 722 that is oriented toward a discharge opening 710 formed in the substrate 701. The filter frit material 712 can be filled with a filtration material 718, eg, an ion exchange gel filtration material. Covers 714 and 716 can be secured, glued, glued or otherwise affixed to substrate 701 using adhesive 715. The adhesive can be, for example, a pressure sensitive adhesive.

  The microfluidic devices 98, 498 and 700 shown in FIGS. 1-6 can be used to filter liquids that are manipulated to pass through the devices. This device can be used, for example, for gel filtration, size exclusion filtration, ion exchange filtration, or a combination of these filtration techniques. For example, the filtering material can be loaded into the device and / or included in the device and can include small beads of filtering material. A size exclusion material that can retain the small molecules of the aqueous sample while allowing the larger molecules of the sample to pass through can be used. For example, P-10 BIO-GEL material from Bio-Rad can be used and is composed of acrylamide particles with an average particle size diameter of approximately 45-90 μm. When these particles are hydrated, they can capture free dye, unwanted nucleotides, and salt ions from the sample as the sample moves through the material.

  Samples can be manipulated through devices 98, 498 and 700, for example, by gravity pressure differential, or centripetal force. The resulting filtrate eluting from the device can then be can be analyzed, used, or subsequently passed through the device to the next stage of processing, for example, a PCR reaction chamber, a sequencing reaction chamber, or It can be passed to other processing reaction chambers.

  According to various embodiments, the filter frit material 112, 412 or 712 shown in FIGS. 1-6 can be “press fit” into each chamber, placed in each chamber, or other methods Can be positioned in each chamber.

  The cover described above may include a plastic material, such as a polyolefin material, with reference to FIGS. According to various embodiments, the cover may include a tape or film material covered with a pressure sensitive adhesive, or a plastic material that is bonded to the respective substrate by heating.

  According to various embodiments, including the embodiments shown in FIGS. 1-6, the device may comprise one or more channels that may be rectangular in cross-sectional shape. The device comprises a channel that can be, for example, about 0.1 mm to about 1.0 cm deep, about 0.1 mm to about 1.0 cm wide, and about 0.1 mm to about 10.0 cm long. obtain. An exemplary channel may be 0.50 mm deep, 0.50 mm wide, and 20 mm long, thus providing a total volume of about 5 μL.

  According to various embodiments, including the embodiments of FIGS. 1-6, the gel filtration material can be placed in the channel of the device. The gel filtration material pulls material into the device by pipetting into the input opening of the device and / or using a vacuum force (eg, applied to the discharge opening of the device) Can be loaded by. The channel of the device may be filled with the gel filtration material by a pressure that loads the gel filtration material through the input opening of the device and provides the gel filtration material to the channel or chamber of the device. In the exemplary embodiment, the fully hydrated gel filtration material is loaded into the channel of the device, eg, the first channel 104 of the device 98 of FIG. Once the channel is filled with hydrated gel filtration material, the device can be centrifuged to dehydrate the gel filtration material and “fill” the gel filtration material to form a purification column. . This process can be used to prepare a device for sample filtration and can be used to remove unwanted or excess water or buffer from the gel filtration material. In a variation of this process, excess water or buffer can be collected in the outlet channel or chamber and later used to dilute and increase the volume of the filtered sample and prepare for sample injection.

  According to various embodiments, including the embodiments of FIGS. 1-6, the device may comprise additional chambers and / or channels. For example, the device may comprise a PCR amplification chamber, a sequencing reaction chamber, or both a PCR amplification chamber and a sequencing reaction chamber. In accordance with various embodiments, the device can include an exhaust chamber useful for holding a sample prior to injecting the sample into an array detection system or other analytical detector.

  In accordance with various embodiments, a microfluidic device is provided that includes multiple sample processing paths in a single device, as described herein.

  According to various embodiments, the porous filter frit material can be used to prevent gel filtration material loaded into the channel from flowing out of the channel. The average pore size of the filter frit material can be selected to limit the movement of gel filtration material (eg, acrylamide beads) while fluid passes through (water, sample, etc.). For example, the microfluidic device shown in FIGS. 1-6 may utilize a hydrophilic polyethylene filter frit material having an average pore size of about 33 microns. When used with a P-10 BIO-GEL gel filtration material, such a frit may properly limit the gel filtration material while allowing water and sample fluid to pass through the gel material. An exemplary porous filter frit material that can be used for such purposes is a sintered, high density polyethylene (HDPE) frit with an appropriate average pore size.

  In accordance with various embodiments, the gel filtration retention mechanism can be provided in the device and includes a flow restriction factor in the form of a small channel or serpentine path that is formed in the substrate and prevents passage of the gel filtration material.

  According to various embodiments, including the embodiments of FIGS. 1-4, when two channels are provided by a filtration chamber or column and separated, one of the channels is formed on the first surface of the substrate. The second channel may be formed on the opposing surface of the substrate. For example, the second channel 108 (FIG. 2) or 408 (FIG. 4) can be formed in the first surface of the substrate and can provide fluid communication between the processing chamber and the respective discharge openings.

  The second channel may be similar to or having the same dimensions as the first channel, as illustrated in FIGS. The second channel can have a depth of about 0.1 mm to about 1.0 cm, a width of about 0.1 mm to about 1.0 cm, and a length of about 0.1 mm to about 10.0 cm. An exemplary second channel has a depth of about 0.50 mm, a width of about 0.75 mm, and a length of about 3.0 mm. The second channel may be defined at least in part by a cover (eg, cover 116 as shown in FIGS. 1 and 2 or profile 416 as shown in FIGS. 3 and 4). Regardless of whether the device comprises a first channel filled with gel filtration material, the second channel of the device can be provided with the gel filtration material loaded therein. The gel filtration material can be loaded into the second channel before, after or simultaneously with the filtration frit being positioned within the device.

  According to various embodiments, the discharge openings 110, 410, 710 can serve to capture or hold the processed sample after the sample has passed through the processing chamber in the microfluidic device. Initially, the discharge openings 110, 410, 710 can be opened so that a vacuum can be applied to the device for loading the gel filtration material. The outlet opening may remain open during centrifugation of the microfluidic device to further fill and / or dehydrate the gel filtration material. During such a filling process, excess water or buffer can be purged from the device and escape from the device through outlet openings 110, 410, 710. When the sample is manipulated through the microfluidic device, such as by centrifugation, the outlet openings 110, 410, 710 are sealed with cover films 116, 416, 716 so that the sample in the device is removed from the device. Try not to lose or otherwise keep the sample in the device.

  In accordance with various embodiments, a microfluidic device having a plurality of paths formed in a substrate can be provided, each path being similar to one of the paths shown in FIGS. For example, the use of channels and chambers having a width of about 0.50 mm or less provides up to 96 or more such paths in the substrate and a standard microtiter tray (eg, a length of about 4. It is possible to provide a resulting substrate size equal to 75 inches and a width of about 3.25 inches. An exemplary device of such design is shown in FIG. 20 and incorporates a 5 μL gel filtration column.

  In accordance with various embodiments, a microfluidic device is provided, which is similar to the device shown in FIGS. 1-4 and is greater than the sum of the first channel depth and the second channel depth. It has a substrate with a thickness. In accordance with various embodiments, a microfluidic device is provided, which is similar to a device having a substrate with the same thickness as the depth of the filter chamber 713 shown in FIGS.

  In accordance with various embodiments, including the embodiments of FIGS. 1-6, a microfluidic device is provided, the filtration frit material 112, 412, 712 having an outer peripheral shape, chambers 106, 406, 713 has an inner peripheral shape, which is complementary to the inner peripheral shape.

  FIGS. 7 and 9 show an exemplary embodiment of an embedded gel filtration frit 750, 950 that is constructed of a form-stable frit material and defines chambers 721, 921 and openings 728, 928. , 772. The chambers 721 and 921 are filled with gel filtration material 778 and 978, and the gel filtration material is loaded into the chambers 721 and 921. The gel filtration frit 750, 950 can be made by the method shown in FIGS. 8 and 10, respectively.

  FIGS. 8 and 10 illustrate nozzle 130 in the process of filling embedded gel filtration frit 750, 950 with diluent 132 and gel filtration material 778, 978 through openings 728, 928.

  FIG. 11 shows an embodiment of a multi-nozzle filling machine 140 for simultaneously filling a plurality of built-in gel filtration frits.

  In accordance with various embodiments, the embedded gel filtration frit 750, 950 can be formed as illustrated in FIGS. 8 and 10 and then a microfluidic device (eg, a device as shown in FIGS. 3-6). Can be filled. For example, a slurry of hydrated P-10 BIO-GEL particles can be pumped into a porous form-stable frit body and the resulting frit can be assembled into a microfluidic device. Such manufacturing procedures can reduce the number of substrate operations associated with forming the microfluidic device, enable off-line filtration frit manufacturing, and reduce the overall manufacturing cost of the microfluidic device.

  According to various embodiments, the body and / or chamber of the embedded gel filtration frit can be constructed in a rectangular-like or cylindrical shape, and the chamber can be constructed of a gel using a single nozzle or multiple nozzles. It can be pre-filled with more than one mold.

  The built-in gel filtration frit can retain the gel filtration material therein and still allow water and liquid samples to flow therethrough.

  In accordance with various embodiments, an embedded gel filtration frit may be provided that includes an opening in the frit body and is in fluid communication with the inner gel filtration material chamber. According to various embodiments, an embedded gel filtration frit having a gel filtration material comprising an ion exchange gel filtration material can be provided. According to various embodiments, an embedded gel filtration frit having a form-stable filter frit body comprising a porous hydrophilic polyethylene material can be provided. The body can also be formed using a membrane or other filter material, but is not necessarily form-stable. The built-in gel filtration frit can have a length dimension, a width dimension, and a depth dimension, where each of these dimensions is less than 50 mm.

  In accordance with various embodiments, a microfluidic device is provided having a channel formed in a substrate and an embedded gel filtration frit disposed in the channel, for example, as shown in FIG. In accordance with various embodiments, channels formed in the substrate, input openings formed in the substrate, discharge openings formed in the substrate, formed in the substrate between the input and discharge openings, and in fluid communication A microfluidic device can be provided having a filtration column or chamber in a state, and an embedded gel filtration frit as described herein disposed in the column. Here, the input opening of the channel is in fluid communication with the opening of the built-in gel filtration frit.

  FIGS. 12-16 illustrate various microfluidic devices 200, each of which is designed with one or more profiles to limit the flow through the device of filtration material. 12 and 14 to 16, these external shapes are formed on the substrate 220. In the device of FIG. 13, the channel can be formed in an insertable component that can be incorporated into a microfluidic device. In each device, the first channel 208 is in fluid communication with the second channel 210. A fluid communication 212 in the form of a region is provided in each device between the first channel 208 and the second channel 210. 12 and 14-16, fluid communication 212 is also formed in substrate 220. Each of FIGS. 12-16 shows a flow restricting material 202 disposed in first channel 208 and / or fluid communication 212. As shown in FIGS. 12 and 13, a second material 204 having a smaller average diameter particle cross-sectional area than the material 202 is provided in the first channel 208. In FIG. 13, a third material 206 having a still smaller mean diameter particle cross-sectional area is provided in the first channel 208. Each of the materials 202, 204, and 206 can include a gel filtration material (eg, an ion exchange gel filtration material). Each of materials 202, 204, and 206 can be a material (eg, glass or silicon seed) having an inert mean diameter particle cross-sectional area as described herein. The microfluidic device 200 may also have a baffle 214 to further restrict the flow of the flow restricting material 202 to the second channel 210, as shown in FIGS. This baffle 214 may be provided in the fluid communication 212, in the second channel 210, or in both the fluid communication 212 and the second channel 210.

  Some of the particles of material 202, 204, and 206 may flow into the second channel 210 before the stack of materials 202, 204, and 206 is formed in the fluid communication 212. Formation of the stack in fluid communication 212 and / or collapse of the stack can be manipulated by controlling how much force is applied to the microfluidic device (eg, centripetal force, or aerodynamic force). The fluid communication 212 can be a tapered moving region (eg, a funnel-shaped moving region). This fluid communication 212 may be a conical moving region, as shown in FIGS.

  In accordance with various embodiments, a method of forming the microfluidic device 200 shown in any one of FIGS. 12-15 is provided. The particulate flow restricting material 202 is disposed in a first channel 208 having a first cross-sectional area. This first channel 208 ends in the form of a region in the fluid communication 212. The particles of the first material 202 can have an average diameter particle cross section that is between 5% and about 90% of the diameter cross section of the second channel 210. According to various embodiments, the additional material 204 is composed of particles having a smaller cross-sectional area than the particles of the first material, which can then be added to the stack of particles 202 of the first material. A third type of material 206 may be added after the particulate material 204, which is another flow-restricted particulate material of the same composition but from either of the particulate materials 202 or 204. Can be a small size, or can be a gel or resin material that can be a non-particulate material. The diluent that is initially associated or used to load the first material and / or the second material is from the first channel 208, through the fluid communication 212, and to the second channel 210. And can be moved using, for example, centripetal force. The diluent can be moved further out of the second channel 210 and can be removed from the device, for example, or stored in a collection or drain chamber.

  According to various embodiments, the particulate materials 202, 204, and 206 can be gel filtration particles or other particles. The particles can be chemically derivatized or physically modified to provide functions other than restricting the flow of the subsequently loaded gel or resin material. For example, materials 202, 204, and 206 can be modified to allow hybridization with DNA or DNA fragments. Where any of the materials 202, 204 or 206 is modified to allow hybridization, a method can be provided by which the hybridized components can be subsequently released from the material, for example by denaturation. . Thus, various embodiments may provide for purification or enrichment of hybridizable components.

  Because the microfluidic device 200 shown in FIGS. 12-16 can be assembled at a suitable location, the method of making the device eliminates utilization and handling issues associated with using filtration frits known in the art. It can be avoided. For example, device 200 can be made smaller than devices incorporating frit known in the art.

  In accordance with various embodiments, a microfluidic device (eg, the device shown in FIGS. 12-16) can be provided, wherein the direction of fluid flow through the first channel is flow through the second channel of fluid. Lined with the direction of. In accordance with various embodiments, a microfluidic device can be provided, wherein at least one of the first channel and the second channel has a round shape and a cross-sectional area perpendicular to the direction of fluid flow (e.g., A circular cross-sectional area).

  In accordance with various embodiments, eg, the embodiments shown in FIGS. 12-16, a microfluidic device comprising a substrate having a first surface, a second surface opposite the first surface, and a thickness can be provided. . The substrate comprises a first channel formed in the substrate and extending in a first direction and having a first cross-sectional area defined by at least a first minimum dimension and a first depth; This first depth extends in a direction perpendicular to the first surface and towards the second surface. The substrate also includes a second channel formed in the substrate and extending in the second direction, wherein the second channel is defined by at least a second minimum dimension and a second depth. Having a second cross-sectional area. This second depth extends in a direction perpendicular to the first surface and towards the second surface. The device further comprises a fluid communication formed in the substrate between the first channel and the second channel and having a third cross-sectional area defined by at least a third minimum dimension. Here, the third cross-sectional area is smaller than the first cross-sectional area. The device further includes a particulate flow restricting material disposed in the first channel and comprising flow restricting particles. Here, at least 10% by weight of the flow restricting particles comprise flow restricting particles having a particle size smaller than the third minimum dimension. According to various embodiments, the first direction and the second direction can be aligned with each other in fluid communication. According to various embodiments, at least one of the first channel and the second channel comprises a cross-sectional area having a round shape. According to various embodiments, at least 50% by weight of the flow restricted particles comprise flow restricted particles having a particle size that is less than the third smallest dimension. For example, at least 95% by weight of the flow restrictive particles include flow restrictive particles having a particle size smaller than the third minimum dimension. According to various embodiments, the flow restricting particles have a particle size that is less than the second minimum dimension. According to various embodiments, the flow restricting material may include a gel filtration material disposed in the first channel and having an average diameter cross-sectional area that is smaller than the third cross-sectional area. The average diameter cross-sectional area of the flow restricting particles can be about 0.1 to about 0.2 times the third cross-sectional area. According to various embodiments, the flow restricting particles can form a stack in fluid communication. The flow restricting material includes a first flow restricting material having particles of a first average diameter that are filled together in fluid communication, and a first filled and filled together in a first channel. A second flow restriction material having a second average diameter particle adjacent to the flow restriction material. Here, the average diameter of the particles of the first flow restriction material is larger than the average diameter of the particles of the second flow restriction material. Further, the second co-filled flow restricting material may be spaced further from the second channel than the co-filled first flow restricting material.

  As shown in FIGS. 16 and 17, a microfluidic device may be provided that changes the fluid communication 212 between the first channel 208 and the second channel 210 with a sudden change in cross-sectional area. Prepared in the form.

  As illustrated in FIGS. 16 and 17, according to various embodiments, the flow through a device of fluid or particulate material is squeezed to meter the distribution of reagents and / or the flow of particulate material in a microfluidic device. It may be desirable to block. Under such circumstances, it may be useful to use a flow restriction factor according to various embodiments. According to various embodiments, a channel having a cross-sectional area substantially smaller than the connecting channel can be used to form a flow restriction factor. Depending on the desired results and restrictions, the dimensions of the restrictions can be selected, for example, to retain smaller particles in the larger cross-sectional connection channels. FIG. 17 shows a typical outline of a flow restriction design that can be used.

  In accordance with various embodiments, one or more flow restriction factors can be used to prevent the flow of gel filtration particles and / or size exclusion media to the connection channel, processing chamber, or drain well. However, this smaller channel can be large enough to allow sample fluid to pass easily. For example, according to various embodiments, the first channel has a first cross-sectional area and a second cross-sectional area that is about 5% to about 50% of the cross-sectional area of the first channel. There may be a discharge end interconnecting the channels. The cross-sectional area of the second channel can be, for example, about 6% to about 30% of the cross-sectional area of the first channel, for example, about 10% to about 15% of the cross-sectional area of the first channel. In an exemplary embodiment, the first channel has a square cross-sectional area having a width of about 0.50 mm and a depth of about 0.50 mm. A second channel is provided in fluid communication with the first channel, which may be a square cross-sectional area having a width of about 0.18 mm and a depth of 0.18 mm. In such a flow restriction factor design, the cross-sectional area of the second channel is about 13% of the cross-sectional area of the first channel. Such a flow restriction factor design may be useful in restricting the passage of gel filtration particles having a minimum dimension of about 0.001 mm or more, for example about 0.01 mm or more, and gel filtration in movement between two channels. Can be useful in causing particle stacking. Here, these gel filtration particles have an average cross-sectional area smaller than that of the second channel, as shown in FIG.

  In such a device, a shoulder is provided at the intersection of the first channel 208 and the second channel 210, the shoulder being perpendicular to the direction of fluid flow through the first channel and the second channel. It can be.

  In accordance with various embodiments, the flow restriction factor of the second channel (eg, second channel 210 in FIGS. 12-17) is formed by opening a valve to form two or more first channels or chambers. , To form a fluid communication with the second channel. The point of intersection or movement between the second channel and the one or more first channels defines the flow restriction factor described herein. This fluid communication can be useful to cause gel filtration stacking in the fluid communication formed by the valve openings. Such valves and the valve utilization techniques described above may include those described in US patent application Ser. No. 10 / 336,274.

  FIG. 18 illustrates a manufacturing process for forming a microfluidic device (eg, the devices of FIGS. 1 and 2). In the first step, a substrate is formed, the substrate comprising input, discharge, first and second channels, and a filtration frit column. In the second step, the filtration frit is positioned in the filtration frit column. Positioning can be accomplished by press fitting the filtration frit onto the column, or depending on tolerances, the filtration frit can simply be placed on the column. In the third step, the bottom surface of the device is sealed with a cover, for example by applying a pressure sensitive adhesive tape to the bottom surface of the substrate. In the fourth step of the method, the top of the filtration frit column is sealed and half of the input and output openings are sealed.

  FIG. 19 illustrates a method of manufacturing a microfluidic device (eg, the device of FIGS. 1 and 2). In the first step, a gel slurry containing flow restricting particles can be filled in the first channel of the device through the input opening. A force can be applied to the device to fill the gel slurry, for example, by using a vacuum at the discharge opening of the device or by applying a centripetal force to the device. The force can move the gel slurry from the input opening to the first channel. This input opening can be completely sealed after loading the gel slurry by applying a cover, or the sealing can be done after the first channel is filled. After the first channel is filled, the gel slurry can be dehydrated and the cover can be applied to seal the outlet opening. The device can then receive the sample for processing. A force can then be applied to the microfluidic device to manipulate the sample from the input opening to the discharge opening.

  According to various embodiments, flow restricting material, gel filtration material and sample may be introduced through the input opening 3 of the device. At any of the various times during the process, the input opening can be completely sealed with a cover (eg, an optically clear adhesive layer cover) over the first surface of the device. This input opening may also be completely or partially sealed over the opposing second surface of the device. This allows confinement of small samples (eg, sample sizes of about 1 nanoliter to about 10 μL, eg, about 100 nanoliters to about 0.5 μl) that can be pipetted into the input opening.

  The various devices and methods described above can be implemented in devices and methods for high throughput processing of multiple samples simultaneously. An example of such a high throughput device is shown in FIG. FIG. 20 is a top view of a microfluidic device 400 having a plurality of pathways 300 for processing respective samples according to various embodiments. The plurality of paths 300 may be parallel to each other. Each pathway 300 may have an input opening 372 in fluid communication with the plurality of respective processing chambers 376, 378, 381, 383, and 385 that can be blocked and / or opened. Each path 300 may end at a respective discharge opening 387, 389 as shown.

  In the device of FIG. 20, each path 300 may include valves 391, 393, and 397 in addition to processing chambers 376, 378, 381, 383, and 385. In various embodiments, each path may also comprise a can include a flow splitter 395. The splitter may divide each path 300 into two respective sub-pathways (eg, a reverse sequencing reaction path and a forward sequencing reaction path). Each sub-path provides a separate exhaust chamber or reservoir 387, 389, respectively.

  FIG. 21 is a top view of another embodiment of a microfluidic device comprising a plurality of pathways 422 in accordance with various embodiments. In accordance with the exemplary embodiment shown in FIG. 21, each pathway 472 includes an input well 424, a PCR chamber 426, a PCR chamber valve 428, a PCR purification chamber 430, a PCR purification chamber valve 432, a PCR purification chamber appendage 434, respectively. A reaction input well 436, a sequencing chamber 438, a sequencing chamber valve 440, a sequencing purification chamber 442, and an exhaust well, chamber, or reservoir 444 (all formed on the substrate 420) may be provided. Exemplary valves that may be useful in this and various other embodiments are described in Bryning et al., US Provisional Patent Application No. 60 / 398,851, which is hereby incorporated by reference in its entirety. Including the described valve.

  22 and 23 are enlarged views of the input chamber of a device (eg, the device shown in FIG. 21), which show a plurality of teardrop-shaped chambers 250 formed in the substrate 260. The teardrop shaped chambers 250 each have a substantially circular first end 252, a narrower and opposite second end 256, and an opening 258 in fluid communication with the channel 254 (which is It may have the following outline of the device (eg resulting in a processing chamber).

  According to various embodiments, the teardrop shaped chamber 250 may have a constant cross-sectional area along the depth of the chamber. According to various embodiments, the bottom of the teardrop shaped chamber can be fan-shaped or flat.

  Since the centripetal force imparted to a linear device need not be in line with each path, channel, well, or chamber of such a device, the dead volume zone is the Can be made in the corner. In accordance with various embodiments, a teardrop shaped chamber 256 can be used to guide the sample to the connecting channel 254 to facilitate complete movement of the sample and to prevent a portion of the sample from being retained. . This design can be used for all non-radial wells and both can be used to the left or right of the center of the device. FIG. 22 shows an exemplary pattern of such wells.

  According to various embodiments, the teardrop shaped chamber can be tilted with respect to the direction of sample flow through the path, or rotated 45 ° to improve sample movement through the path. The direction of tilt may depend on the position of the well with respect to the axis of rotation of the device or spinning platen where the device is held, attached, affixed, or fixed.

  In accordance with various embodiments, a method for manipulating a liquid sample in a microfluidic device is provided. The device has a teardrop shaped chamber and a liquid sample disposed in the chamber. This device can be rotated about an axis of rotation. This axis of rotation is not present in any part of the device. This rotation can impart centripetal force to the liquid sample from the chamber to the channel. A method for centripetally manipulating a liquid sample into a chamber in a channel is also provided.

  FIG. 24 is a top view of a microfluidic device having a path 300 for processing a sample according to various embodiments. FIG. 25 is an enlarged top view of the path 300 shown in FIG. The route 300 is an example of the route 300 shown in FIG. This path 300 includes an input chamber 302, an input channel 304, a PCR chamber 306, a PCR chamber valve 308, a PCR purification column 310, a PCR purification column valve 312, a flow splitter 334, a flow splitter valve 314, a forward sequencing reaction chamber 315, Reverse sequencing reaction chamber 316, sequencing reaction chamber valves 318, 319, forward sequencing reaction purification column 323, reverse sequencing purification column 320, forward sequencing column valve 321, reverse sequencing reaction column valve 322 , Forward sequencing reaction product discharge chamber 326, as well as reverse sequencing reaction product discharge chamber 324. The device shown in FIG. 24 is also shown to include a substrate 368 and a cover 360.

  According to various embodiments, channels, chambers, valves and other components of microfluidic devices having parallel paths can be from each other, eg, 9 mm, 4.5 mm, 3 mm, 2.25 mm, 1.125 mm, or 0. This path 300, which can be spaced apart by .5625 mm, can be parallel and can be positioned and attached to the rotating platen so that it does not exist on the radius of rotational motion. For further details regarding microfluidic devices having externally parallel processing paths, systems and apparatuses including or for processing such devices, see co-filed US patent application Ser. No. 10 / 336,274. No. 10 / 336,330, both of which are hereby incorporated by reference in their entirety.

  According to various embodiments, the device can be pipet loaded. Prior to injecting the sample, the device can be preloaded with suitable reactants, reagents, buffers, or other conventionally known components useful for performing the desired reaction in the device.

  According to various embodiments, the microfluidic device can be a stacked, multi-layer polymeric material device that can be adapted to the SBS microplate format. The microfluidic device can be about 0.5 mm to about 5 mm thick, such as about 2.0 mm to about 3.0 mm thick. In its basic form, the microfluidic device can comprise a substrate laminated on both sides with thin cover films. Within this substrate is a series of channels, chambers, and / or wells that can be used to manipulate the sample fluid along a predetermined path. The fluid sample can be moved from the channel or chamber to the channel or chamber by centripetal force. The centripetal force can be generated by rotating the device about the axis of rotation while attached to the rotating platen. Thus, the sample fluid can be moved from one end of the device to the other as the various reactions occur sequentially.

  The device can be rotated so that fluid moves through the device under centripetal force, even if the entire path of the device is sealed.

  According to various embodiments, the processed sample resulting from the use of the microfluidic device can be an aqueous, ready-to-inject sample. This sample can be used, for example, in a capillary electrophoresis analysis instrument.

  According to various embodiments, the device can include a purification column that can allow for the purification of small amounts (eg, a volume of about 1 nanoliter to about 10 μl, eg, about 100 nanoliters to about 0.5 μl). Various embodiments allow for the purification of small samples in a high throughput, parallel planar format.

  In accordance with various embodiments, a microfluidic device is provided, the substrate having a rectangular substrate.

  According to various embodiments, a microfluidic device is provided, the device comprising a path having a path having a first channel and a first chamber at least partially formed in a substrate. Here, the substrate comprises a plurality of such paths. Each respective chamber has a depth, and a teardrop-shaped cross-sectional area when sectioned perpendicular to this depth. The respective chambers each have a substantially circular first end and a narrower and opposite second end. The second end of each chamber is in fluid communication with the respective channel. In accordance with various embodiments, a microfluidic device is thus provided, the device having a plurality of such pathways arranged parallel to each other.

  According to various embodiments, a microfluidic device is provided that includes a plurality of parallel sample processing paths and at least one valve along each path. The at least one valve includes a first recess formed in the substrate, a second recess formed in the substrate, and an intermediate wall sandwiched between the first recess and the second recess. Can be provided. Here, the intermediate wall portion is formed from a deformable material having a first elasticity. The valve may also include an elastically deformable cover layer that covers the first recess and the second recess and has a second elasticity greater than the first elasticity. In other words, the cover layer can be more elastic than the intermediate wall material, or it can rebound faster. This elastically deformable cover layer can be in contact with the intermediate wall when the intermediate wall is in an undeformed state and is not in contact with the intermediate wall when the intermediate wall is in a deformed state. Thereby creating fluid communication between the first and second recesses. Further details of such valves can be found in US Provisional Patent Application No. 60 / 398,851 (filed Jul. 26, 2002), and US Patent Application No. 10 / 336,274 (2003) filed at the same time. (Filed Jan. 3, year) (both of which are hereby incorporated by reference in their entirety).

  According to various embodiments, a microfluidic device is provided, the device comprising a plurality of parallel processing paths and at least one valve along each path, wherein the at least one valve is formed in a substrate. And a first recess comprising a first recess portion and a second recess portion. The first recess is at least partially defined by the opposing wall surface portion. The opposing wall surface portion includes a first deformable material having a first elasticity. The first recess portion and the second recess portion are in fluid communication with each other when the first deformable material is in an undeformed state. The at least one valve also includes an elastically deformable cover layer having a second elasticity greater than the first elasticity. In other words, the cover layer can be more elastic or rebound faster than the deformable opposing wall surface portion. This cover layer covers at least the first concave portion. The opposing wall surface portion including the first deformable material forms a barrier wall sandwiched between the first recessed portion and the second recessed portion, and the barrier wall is in a deformed state. It can be modified to prevent fluid communication between the first recess portion and the second recess portion.

  According to various embodiments, the substrate of the microfluidic device can include a single layer material, a coated layer material, a multilayer material, or a combination thereof. Exemplary substrates can include a single layer substrate of a hard plastic material (eg, a polycarbonate material). Materials that can be used for the microfluidic device or components thereof (eg, substrate, base layer, recess-containing layer, or any combination of components) include polycarbonate, polycarbonate / ABS blends, ABS, polychlorinated Vinyl, polystyrene, polypropylene oxide, acrylic, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), PBT / PET blend, nylon, blend of nylon, polyalkylene material, fluoropolymer, cycloolefin polymer, or these Combinations may be mentioned. According to various embodiments, the substrate material is a cyclic olefin copolymer (eg, ZEONEEX available from ZEON Corporation, Tokyo, Japan or TOPAZ available from Ticona GmbH, Frankfurt, Germany).

  The entire substrate can include an inelastically deformable material. In accordance with various embodiments having a valve with an intermediate wall, at least the intermediate wall may include a non-masculine deformable material. This intermediate wall need not be inelastic but is sufficiently inelastic and deformable to allow the formation of fluid communication between the two recesses (the intermediate wall separates upon deformation of the intermediate wall). possible. According to various embodiments, the substrate can include a material that can withstand thermal cycling at temperatures between 60 ° C. and 95 ° C., for example, as used in polymerase chain reaction. Furthermore, the substrate material provides the force necessary to achieve manipulation of the fluid sample through the microfluidic device (eg, centripetal force required to rotate and manipulate the sample within and through the device). Can be strong enough to withstand.

  The substrate can include one or more base polymers in contact with the recess-containing layer. The recess-containing layer can be a layer having a hole formed through the layer, and the base layer can be in contact with the recess-containing layer and can define a bottom well of the through-hole in the recess-containing layer. The substrate can have the same dimensions as the microfluidic device and can constitute a major portion of the thickness of the microfluidic device.

  In accordance with various embodiments, a microfluidic device can be provided that includes an elastically deformable cover layer that at least covers a portion of a recess-containing substrate in a region where the portion of the substrate is to be deformed. Prepare. For example, the cover layer can cover any number of multiple chambers or channels formed in the substrate, or can cover all of the chambers and channels formed in the substrate. The cover layer may partially cover one or more chambers, input openings, discharge openings, columns, or other features formed on or on the substrate. This cover layer allows the cover layer to be temporarily deformed when a deformer contacts the device and deforms the intermediate wall (eg, the intermediate wall located below the cover layer). May have elastic properties. Once such a deformation factor is removed from contact with the microfluidic device, the deformable intermediate wall is fluidized by two or more recesses (fluidized by deformation of the intermediate wall) while the cover layer is elastically rebounding. It can remain deformed for at least sufficient time to allow fluid movement between). The deformable material of the intermediate wall can be elastic to some extent or inelastic.

  The elastically deformable cover layer and / or substrate can be chemically resistant and inert. This elastically deformable cover layer may comprise a material that can withstand thermal cycling at temperatures between about 60 ° C. and about 95 ° C., for example, as used in the polymerase chain reaction. Any suitable masculine deformable film material (eg, elastic material) can be used for the cover layer. According to various embodiments, the PCR tape material can be used as or in conjunction with an elastically deformable cover layer. Polyolefin material films, other polymer films, copolymer films, and combinations thereof can be used for the cover layer.

  The cover layer can be a semi-rigid plate that bends over its width or length, or that bends or deforms locally. The cover layer can be about 10 micrometers (μm) to about 500 μm thick, for example, 50 μm to about 100 μm, and can include an adhesive layer. If used, the adhesive layer can be about 50 μm to about 100 μm thick. Other materials, features, and aspects of microfluidic devices, device substrates, device cover layers, and device walls are described in Bryning et al. US Provisional Patent Application No. 60 / 398,851 (incorporated herein in its entirety). Incorporated herein by reference).

  FIG. 26 shows a microfluidic device processing system 399 that holds and secures a platen 380 that rotates about an axis of rotation 386, each microfluidic device (eg, the devices shown in FIGS. 20 and 21). Holders 381 and 383, a heating element 388 and a control unit 390. The processing system also includes a drive unit (not shown) and a control unit (not shown) for the drive unit. FIG. 26 shows the direction of rotation with unmarked arrows, but the direction of rotation could instead be the opposite direction.

  Figures 27a-27d are cross-sectional views of various channel profiles that may be used in microfluidic devices according to various embodiments. In FIG. 27 a, the channel 542 is formed with a rectangular cross-sectional area in the substrate 540. This cross-sectional area may have an aspect ratio (which is a width / depth ratio) greater than one. In FIG. 27b, the channel 546 is formed in the substrate 544 with a semi-elliptical cross-sectional area. This cross-sectional area may have an aspect ratio (ie, width / depth ratio) greater than one. In FIG. 27c, a thin and narrow channel 550 is formed in the substrate 548, where the cross-sectional area can have an aspect ratio (ie, width / depth ratio) of less than one. In FIG. 27d, the channel 554 is formed in the substrate 552 with a trapezoidal cross-sectional area. These and other cross-sectional designs can be used as flow restricting channels and can be performed or formed during valve-opening operations according to various embodiments.

  A typical straight channel flow limiting factor cross-sectional dimension feature can be, for example, about 0.2 mm x about 0.2 mm. The length of such a channel can be, for example, from about 0.1 mm to about 10 cm, such as about 5 mm. The flow restriction factor can be used with larger chambers (greater than about 0.50 mm) and can serve to retain particles (eg, P-10, SEIE beads, particles, and SEC beads) located in the chamber. This flow restriction factor may be located downstream of the chamber holding the particles. Downstream means that the flow limiting factor is located at a distance farther from the axis of rotation than the chamber. When subjected to centripetal force, the material in the chamber can move toward a flow limiting factor. In this chamber, particles can be retained, but fluid can pass to an adjacent channel or chamber.

  According to various embodiments, and as described above, the size of the flow restriction factor is not limited to a square cross-sectional area. Other shapes can be successfully implemented. For example, a rectangular cross-sectional area of a flow restriction factor having a depth of 0.10 mm and a width of 0.30 mm is formed on a substrate to hold a gel filtration medium (eg, P-10 beads commercially available from BioRad). Can be done.

  According to various embodiments, the processing system can comprise a microfluidic device holder on the platen. The platen orients parallel paths of the microfluidic device off-center with respect to the platen axis of rotation. In accordance with various embodiments, a holder can be provided that can provide all the parallel paths of the microfluidic device such that all of the paths deviate from the radius when the path is parallel to the radius of the platen. And so that they are on the same side of the radius.

  In accordance with various embodiments, a sample processing system is provided comprising a microfluidic device, the device having a plurality of parallel paths disposed in a holder. Here, each input opening of the plurality of paths is closer to the rotation axis than each discharge opening of the plurality of paths. According to various embodiments, each of the plurality of parallel paths of the device comprises a respective input opening, at least one processing chamber, and an exhaust opening in a linear arrangement.

  According to various embodiments, the microfluidic device used with the sample processing system is shaped as a rectangle having a length, width, and thickness, and the holder can hold the microfluidic device firmly to its platen. . Clips, fasteners, or other retaining mechanisms can be employed to secure the device to the platen. In accordance with various embodiments, a sample processing system is provided, wherein the microfluidic device has opposing first and second rectangular surfaces. Here, each of these surfaces has a length greater than its width. In accordance with various embodiments, a sample processing system is provided, wherein the microfluidic device is disposed in a holder and the platen radius is perpendicular to the length of the microfluidic device, the device being the length of the device. With parallel paths extending parallel to the length or width. In accordance with various embodiments, a sample processing system is provided, wherein the microfluidic device is disposed in a holder, the platen radius is perpendicular to the width of the microfluidic device, and the device is the length of the device. With parallel paths extending parallel to the length or width.

  A description of other material components and methods useful for various configurations of the microfluidic devices, systems, and methods described herein can be found in U.S. Provisional Patent Application No. 60 / 398,851 to Brying et al. Incorporated herein by reference).

  The foregoing description and other sample processing devices can be processed alone. According to various embodiments, the sample processing device 610 can be mounted on a carrier 680. Such an assembly is shown in an enlarged perspective view of the sample processing device 610 and carrier 680 shown in FIG.

  By providing a carrier that is separate from the sample processing device, the thermal mass of the sample processing device is adjusted to a thickness suitable for handling by automated equipment (eg, by a robot arm) and / or processing by conventional equipment. Compared to manufacturing an entire sample processing device with minimal impact. Another potential advantage of the carrier is that the sample processing device may tend to wind a flat configuration or otherwise deviate from such a configuration. By attaching the sample processing device to the carrier, the sample processing device can be held in a flat configuration for processing. According to various embodiments, the carrier can be made from a plastic material or other rigid material that provides a carrier that is sufficiently rigid when attached to a sample processing device. The plastic carrier can be provided with a rubber pad attached to at least one surface thereof. A silicon foam pad or silicon foam layer can be used on the surface of the carrier (eg, the surface in contact with the sample processing device).

  A carrier can be provided, the carrier having a limited area in contact with the sample processing device to which the carrier is attached, and heat transfer between the sample processing device and the carrier can be reduced. A single unit is attached to this device. The surface of the carrier facing away from the sample processing device may be, for example, a platen or other structure (between the carrier and the platen or other structure by applying a force on the sample processing device towards the heat block. The area in contact with (used to reduce heat transfer) may be provided in a limited manner. The carrier can have a relatively low amount of heat to avoid affecting temperature changes in the sample processing device.

  In accordance with various embodiments, the carrier may have some support so that the carrier and / or attached sample processing device may conform to the surface between which the assembly (eg, heat block and platen is compressed). May show compliance. The carrier itself may not be perfectly flat, for example due to variations in manufacturing tolerances. Further, the assemblies can have different thicknesses due to thickness variations in the carrier and / or sample processing device.

  In accordance with various embodiments, the sample processing device 610 can be loaded using centripetal force. The carrier can maintain the integrity of the sample processing device by applying pressure to the card during loading and / or thermal cycling.

  The carrier 680 can be attached to the sample processing device 610 in a manner that allows the carrier 680 to be reused with many different sample processing devices 610. According to various embodiments, the carrier 680 can be permanently attached to a single sample processing device 610. As a result, after use, both the sample processing device 610 and the carrier 680 are discarded together.

  In the illustrated embodiment, the sample processing device 610 includes a shaped post 611 for aligning the sample processing device 610 with respect to the carrier. At least one of the shaped struts may be located proximal to the center of the sample processing device 610. Although only one shaped post 611 can be used to attach the sample processing device 610 to the carrier 680, at least two posts 611 can be provided. A centrally located support post 611 can assist in centering the sample processing device 610 on the carrier 680. On the other hand, a second strut 611 may be provided to prevent rotation of the sample processing device 610 relative to the carrier 680. Further, although only two struts 611 are shown, it is understood that more than two struts or other attachment sites can be provided between the sample processing device 610 and the carrier 680. Further, the struts 611 can be melt bonded to the sample processing device 610 to achieve the attachment of the two components in addition to the alignment.

  A strut or other alignment profile is provided on either or both of the sample processing device 610 and the carrier 680 so that the molded strut 611 can be used prior to final alignment and attachment to the sample processing device 610. The processing device 610 and the carrier 680 can be approximately aligned. The struts and / or other alignment profiles may align the assembly comprising the sample processing device 610 and the carrier 680 with, for example, a heat treatment system used to thermally circulate material in the sample process chamber 650. One or more alignment profiles can also be used with a detection system for detecting the presence or absence of a selected analyte in the process chamber 650.

  According to various embodiments, struts or other alignment mechanisms may be provided on the carrier 680 to align the carrier 680 and the heat block. The struts can be configured as conical or tapered pins that can mate with corresponding truncated or non-truncated conical or tapered wells or recesses formed in the heat block. . The struts can be configured to have a cruciform cross-sectional area (the tip of a Phillips screwdriver), which can be compressible and / or elastic, such as a conical or tapered well formed in a heat block or Can fit into the recess. The support 680 struts can be made of polypropylene. The well or recess formed in the heat block may have a truncated conical shape.

  The carrier 680 may comprise various contours, such as openings 682, preferably aligned with the process chamber 650 of the sample processing device 610. By providing an opening 682, the process chamber 650 can be examined through the carrier 680. One alternative to providing the aperture 682 is to make the carrier 680 from a material that is transparent to electromagnetic radiation of the desired wavelength. The carrier 680 can be continuous with the surface of the sample processing device 610. That is, the carrier may be provided without a hole formed therethrough for access to the process chamber 650.

  This sample processing device 610 and carrier 680 are illustrated in FIG. Here it can be seen that the loading chamber 630 can extend beyond the periphery of the carrier 680. In this manner, the portion of the sample processing device 610 comprising this loading structure 630 can be removed from the remaining portion of the sample processing device 610 after dispensing sample material to the process chamber 650.

  The carrier 680 illustrated in FIGS. 28 and 29 may also provide advantages in sealing or separating the process chamber 650 during and / or after loading of sample material in the process chamber 650.

  FIG. 30 is an enlarged view of a portion of the bottom surface of the carrier 680, ie, the surface of the carrier 680 facing the sample processing device 610. The bottom surface of the carrier 680 has a number of outlines including a main conduit support rail 683. This support rail may extend along the length of the main conduit 640 in the associated sample processing device 610. This support rail 683 is compressed, for example, while the main conduit 640 of the sample processing device 610 is deformed to separate the process chamber 650 and / or seal the conduit 640 as discussed above. It can provide a surface that can be made.

  In addition to using them during deformation of the main conduit 640, its support rail 683 can also be relied upon during a heat treatment that applies pressure to the conduit 640, for example. Further, the use of support rails 683 is also necessary to seal the main conduit 640 to the device 610 while these support rails provide significantly reduced contact between the sample processing device 610 and the carrier 680. A further advantage may be provided in terms of providing a flexible support.

  Contact between the carrier 680 and the device 610 can be reduced or minimized if the assembly is used in heat treatment of sample material (eg, as used in polymerase chain reaction (PCR)). . Thus, the carrier 680 can be characterized as comprising a carrier body that is spaced from the sample processing device 610 between the main conduits 640 when the support rail 683 is aligned with the main conduit 640. . The void formed between the carrier body and the sample processing device 610 can be occupied by air or, for example, by a compressible and / or insulating material. According to various embodiments, the carrier 680 can be made from plastic and attached to the surface facing the sample processing device 610 or this to reduce heat transfer between the sample processing device 610 and the carrier 680. It may have a layer of compressible foam adjacent to the surface. According to various embodiments, the foam layer can be a silicone foam.

  A number of optional compression structures 684 are also shown in FIG. This structure is in the form of a collar configured to align with the process chamber 650 over the sample processing device 610 in the illustrated embodiment. This collar may define one end of each of the openings 682 and extend through the carrier 680 to allow access to the process chamber 650 above the sample processing device 610. This compression structure 684 (eg, collar) is close to each of the process chambers 650 on the sample processing device 610 when the two components (sample processing device 610 and carrier 680) are compressed against each other. It is designed to compress a separate area of the device in position.

  A separate region of compression may provide advantages such as, for example, improving contact between the device 610 and a heat block proximal to each of the process chambers. The improved contact can enhance the transfer of thermal energy to and / or from the process chamber. Furthermore, the improvement in heat transfer is balanced at least in part by only limited heat transfer to the structure of the carrier 680 itself, due to the limited contact area between the sample processing device 610 and the carrier 680. Can be taken.

  Another advantage of selectively compressing separate areas of the device 610 is that any weakness of adhesion, adhesive stripping, and / or liquid leakage from the process chamber 650 is reduced or reduced by separate areas of compression. It can be disturbed. This advantage may be particularly advantageous when using a compressed structure in the form of a collar or other shape surrounding at least a portion of the process chamber on the sample processing device.

  The collar in the exemplary embodiment is designed to extend only partially around the outer periphery of the process chamber 650 and is not designed to occlude supply conduits that enter the process chamber 650. Alternatively, however, the collar may be designed to occlude the supply conduit, thereby providing further potential further enhancement of separation between process chambers during heat treatment of the sample material.

  The collar 684 optionally provides a barrier to the transmission of electromagnetic energy (eg, infrared to ultraviolet) between the process chambers 650 during processing and / or analysis of the process chamber 650, thereby providing a process chamber. It may provide some reduction in cross-talk between 650. For example, the collar 684 may be impermeable to selected wavelengths of electromagnetic radiation. Alternatively, the collar 684 can inhibit the transmission of electromagnetic radiation of a selected wavelength by diffusing and / or absorbing. For example, the collar 684 may comprise a textured surface to enhance scattering and / or the collar 684 is incorporated into the body of the collar 684 and / or enhances absorption and / or diffusion. A material provided in the coating may be provided.

  This carrier 680 is on the top surface of the carrier 680 (ie, away from the sample processing device, into a compressed structure (eg, in the form of a collar 684 in the exemplary embodiment), and ultimately the sample processing device itself. A force transmission structure for enhancing the transmission of force from the surface facing the surface.

  FIG. 31 shows a portion of an exemplary embodiment of a force transmission structure. This force transmission structure is provided in the form of an arch 685 that includes four openings 682 and is operably attached to the collar 684. This force transmission structure defines a landing area 687 located between the openings 682 and connected to the collar 684 so that the force applied to the joint area 687 in the direction of the sample processing device. 686 is communicated to each of the collars 684 from there to a sample processing device (not shown). In the embodiment shown, the joint area is provided by the top of the arch 685.

  The arch 685 may transmit force uniformly between the different collars 684 attached to the arch 685. This is essentially provided as a hollow column that supports the arch 685 (via the opening 682). This basic structure is repeated for the entire surface of the carrier 680, for example, as can be seen in FIG.

  The advantage of providing a joint area on the force transmission structure includes a corresponding contact between the carrier 680 and other structures used to compress the sample processing device using the platen or carrier 680. Decrease. The reduced contact may provide reduced heat transfer between the carrier 680 and other structures used to compress the platen or sample processing device. Furthermore, this force transmission structure and the corresponding compression structure on opposite sides of the carrier all reduce the amount of material in the carrier 680, thereby reducing the carrier 680, then the carrier 680 and the sample processing device. This can contribute to reducing the amount of heat in the assembly.

  FIG. 32 illustrates another optional profile of the carrier used with the present invention. The carrier 680 'is shown with an optical component 688' (eg, a lens) that can assist in collecting or emanating electromagnetic energy directed to the process chamber 650 '. Although this optical component 688 'is shown as being integral with the carrier 680', it should be understood that the optical component 688 'can be provided as a separate article attached to the carrier 680'. .

  FIG. 33 illustrates yet another optical profile of a carrier that can be used. The carrier 680 "includes an alignment structure 687" that assists in guiding the pipette 611 "or other sample material delivery device to an appropriate loading structure on the sample processing device 610". Can be used to This alignment structure 687 "can be removed along with the loading structure on the sample processing device 610" described herein. This alignment structure 687 ″ can be generally conical as shown to guide pipette 611 ″ to the loading structure on sample processing device 610 ″ when slightly off-center from the inlet port. .

  As an alternative shaped carrier shown in FIGS. 28-31, the carrier may be in the form of a sheet of material in contact with one side of the sample processing device. FIG. 34 is an exploded view of one exemplary sample processing device 710 and carrier 780 that may be used with the sample processing device 710.

  The sample processing device 710 comprises a set of process arrays 720. Each of the process arrays comprises a process chamber 750 configured as an array on the surface of the sample processing device 710 at the sample processing device 710 shown. The carrier 780 includes a plurality of openings 782 formed in the carrier. This opening is preferably aligned with the process chamber 750 when the sample processing device 710 and the carrier 780 are compressed together.

  The carrier 780 can be made from a variety of materials, but it may be preferred that the carrier can be made from a compressible material (eg, a compressible foam or sheet of other material). In addition to compressibility, the compressible material may exhibit low thermal conductivity, low heat content, and / or a low compression set, particularly at temperatures at which sample processing devices may be provided. One class of suitable foams may include, for example, silicone-based silicone foams.

  If the carrier 780 is made from a compressible material, it may not be necessary to provide a relief on the surface of the carrier 780 facing the sample processing device 710 to prevent premature blockage of the conduits in the process array 720. However, if the carrier 780 is manufactured from a more rigid material, it may be desirable to provide some relief on the surface of the carrier 780 for the conduits in the process array 720.

  Similar to the carrier 680 described above, the carrier 780 (eg, as described in FIG. 34) is a sample in the region occupied by the process chamber 750 due to the absence of material located above the process chamber 750. By not compressing the processing device, selective compression of the sample processing device may be provided. As a result, this carrier 780 may provide several additional advantages. For example, weakening adhesion, peeling of the adhesive, and / or liquid leakage from the process chamber 750 can be reduced or prevented by compression applied to the sample processing device 710 surrounding the process chamber 750. Further, for example, heat leakage from a heat block to which the assembly can be pressed can be reduced if the material of the carrier 780 is provided with the desired thermal properties (eg, low heat, low thermal conductivity, etc.).

  In accordance with various embodiments, the opening 782 provides a barrier to the transmission of electromagnetic energy (eg, light) between the process chambers 750 during processing and / or analysis of the process chamber 750, thereby providing a process chamber 750. May provide protection from crosstalk between the two. For example, the carrier 780 can be opaque and / or opaque to selected wavelengths of electromagnetic radiation. Alternatively, the carrier can inhibit the transmission of electromagnetic radiation of a selected wavelength by diffusion and / or absorption. For example, the aperture 782 may comprise a textured surface to enhance scattering. Further, the carrier 780 can include a material incorporated into the body of the carrier 780 and / or provided in a coating thereon, which material can absorb and / or diffuse selected wavelengths of electromagnetic energy. Can be enhanced.

  According to various embodiments, the carrier described above with respect to FIGS. 28-34 can be fixedly attached to the sample processing device, or the carrier can be separate from the sample processing device. If separated, the carrier can be removably attached to or contact each sample processing device in a manner that facilitates removal from the sample processing device without significantly destroying the carrier. . As a result, the carrier can be used with more than one sample processing device. Alternatively, the carrier can be secured to the sample processing device. As a result, both components can be discarded after use. In some examples, the carrier can be attached to a sample processing device, such as a system used to process a platen of a thermocycling system. As a result, when the sample processing device is loaded into the heat treatment, the carrier can be placed in contact with the sample processing device.

  Both of the above carriers are examples of means for selectively compressing together the first and second sides of the sample processing device around each of the process chambers. This compression can occur simultaneously for each process chamber. Many other equivalent structures achieve the function of selectively compressing the first and second sides of the sample processing device together around each of the process chambers, and these structures are: Can be envisioned by those skilled in the art. In some configurations, the means for selectively compressing (eg, elastic carrier 780) may apply a compressive force to substantially all of the sample processing device from outside the process chamber. In other embodiments, the means for selectively compressing applies a compressive force only to a local region (eg, carrier 680 with its associated collar) around each of the process chambers in the sample processing device. obtain.

  Any system that incorporates means for selectively compressing means for attaching the means for selectively compressing to a sample processing device or platen or other structure that is in contact with the sample processing device during processing. Can be used. FIG. 35 describes one thermal processing system that may be used with a sample processing device in block diagram form. The system includes a sample processing device 710 'positioned over a thermal block 708'. The temperature of thermal block 708 'is preferably controlled by thermal controller 706'. On the opposite side of the sample processing device 710 ', means for selectively compressing in the form of a carrier 780' is located between the sample processing device 710 'and the platen 704'. The platen 704 'can be thermally controlled by a thermal controller 702' if desired. This thermal controller may in some cases be the same as the controller 706 'that controls the temperature of the thermal block 708'. This sample processing device 710 ′ and the means for selectively compressing 780 ′ include a platen 704 ′ and a heat block 708 ′ during heat treatment of the sample processing device 710 ′, as indicated by arrows 701 ′ and 702 ′. Can be compressed between.

  Those skilled in the art can now appreciate from the foregoing detailed description that the broad teachings herein can be implemented in a variety of forms. Thus, although the devices, systems, and methods described herein have been described in connection with specific embodiments and examples thereof, the true scope of the present teachings should not be so limited Absent. Various changes and modifications can be made without departing from the scope of the present teachings.

FIG. 1 is a top view of a microfluidic device according to one embodiment. Here, the first channel is formed on the first surface, the second channel is formed on the second surface, and the constant diameter interconnecting column has a frit material disposed thereon. 2 is a side cross-sectional view of the microfluidic device shown in FIG. 1 taken along line 2-2 of FIG. FIG. 3 is a top view of another embodiment of a microfluidic device comprising an embedded gel filtration frit. 4 is a side cross-sectional view of the microfluidic device shown in FIG. 3 taken along line 4-4 of FIG. FIG. 5 is a top view of a microfluidic device according to one embodiment comprising an embedded gel filtration frit. 6 is a side cross-sectional view of the microfluidic device shown in FIG. 5 taken along line 6-6 of FIG. FIG. 7 is a perspective view of an embedded gel filtration frit having a form-stable body, a chamber in the body, and a gel filtration material disposed in the chamber. FIG. 8 is a side cross-sectional view of an embedded gel filtration frit with a form-stable body filled with gel filtration material by using a nozzle as shown in FIG. FIG. 9 is a perspective view of a form-stable body for use in preparing an embedded gel filtration frit and having a chamber. 10 is a side cross-sectional view of the form-stable body shown in FIG. 9 and filled with gel filtration material by using a nozzle. FIG. 11 is a perspective view of a multi-nozzle machine useful for simultaneously filling a plurality of built-in gel filtration frits. FIG. 12 is a top view of a partial cross-section of a microfluidic device having a fluid communication having a conical shape and including two types of particle sizes. FIG. 13 is a top view in partial cross section of a side view embodiment of a microfluidic device comprising a gel filtration material that can be used as a flow restricting factor. FIG. 14 is a top view in partial cross section of an embodiment of a microfluidic device having a baffle that restricts fluid flow and causes gel filtration particle stacking. FIG. 15 is a top view in partial cross-section of an embodiment of a microfluidic device, the microfluidic device having baffles that restrict fluid flow and cause gel filtration particle stacking. FIG. 16 is a top view of various embodiments of a microfluidic device comprising a fluid communication having an abrupt change in cross-sectional area between a first channel and a second channel. FIG. 17 is a top view of various embodiments of microfluidic Debye with fluid communication having abrupt changes in cross-sectional area between a first channel and a second channel. FIG. 18 is a flowchart illustrating a method for forming a microfluidic device with corresponding cross-sectional views. FIG. 19 is a flowchart illustrating a method of preparing a microfluidic device for use as a purification device. FIG. 20 is a top view of an embodiment of a microfluidic device having a substrate, a plurality of parallel pathways formed in the substrate, and a plurality of valves for each pathway. FIG. 21 is a perspective view of an embodiment of a substrate having a plurality of paths. FIG. 22 is a top view of an embodiment comprising a plurality of teardrop shaped chambers disposed on a cant and formed in a substrate. FIG. 23 is an enlarged perspective view of an embodiment of a teardrop shaped dispensing chamber having a tapered cross section. FIG. 24 is a top view of a microfluidic device according to an embodiment having a path for processing a sample. 25 is an enlarged perspective view of the path shown in the device of FIG. FIG. 26 is a perspective view of an embodiment of a microfluidic system comprising a microfluidic device held on a rotatable platen. The platen can be rotated by a drive unit, heated by a heating element, and controlled by a control unit. Figures 27a-27d are cross-sectional views of microfluidic channels having various profiles in the substrate. FIG. 28 is an exploded perspective view of an assembly comprising a sample processing device and a carrier. FIG. 29 is a perspective view of the assembly of FIG. 28 when assembled. FIG. 30 is an enlarged view of a portion of the carrier showing a set of main conduit support rails and collars useful in separating the process chambers on the sample processing device. FIG. 31 is a partial cross-sectional view of a portion of a carrier, illustrating an example of a force transmission structure useful within the carrier. FIG. 32 is a partial cross-sectional view of a sample processing device comprising a carrier and optical elements in the carrier. FIG. 33 shows a sample processing device comprising an alignment structure for the carrier and the sample processing delivery device. FIG. 34 is an exploded perspective view of another sample processing device and carrier assembly according to various embodiments. FIG. 35 is a block diagram of a heat treatment system that may be used with a sample processing device.

Claims (97)

A microfluidic device comprising:
A substrate having first and second opposing surfaces and thickness;
A first channel formed on the first surface and having a first depth extending in a direction perpendicular to the first surface and toward the second surface, the first channel comprising: A first channel having a depth less than the thickness of the substrate;
A second channel formed in the second surface and having a second depth extending in a direction perpendicular to the second surface and toward the first surface, wherein the second channel A second channel, the depth being less than the thickness;
A column providing a fluid connection between the first channel and the second channel, the column from the at least one of the first surface and the second surface to the first surface; And a column extending toward the other of the second surfaces; and a filter frit material disposed in the column;
A microfluidic device comprising: The microfluidic device of claim 1, wherein the column has a height extending from the first surface to the second surface, and from the first surface to the second surface, the first surface. A microfluidic device having a constant cross-sectional area along a plane lying parallel to the surface of the device. 2. The microfluidic device according to claim 1, wherein the height of the column is the same as the thickness of the substrate. The microfluidic device according to claim 1, further comprising a first cover connecting the first surface of the substrate. The microfluidic device according to claim 1, further comprising a second cover connecting the second surface of the substrate. 2. The microfluidic device of claim 1, wherein the filter frit has an outer peripheral shape, the column has an inner peripheral shape, and the outer peripheral shape is complementary to the inner peripheral shape. A microfluidic device. The microfluidic device of claim 1, further comprising a gel filtration material disposed in the first channel. 8. The microfluidic device according to claim 7, wherein the gel filtration material comprises an ion exchange material. 2. The microfluidic device of claim 1, wherein a plurality of first channels formed on the first surface, a plurality of second channels formed on the second opposing surface, and Each of the plurality of columns, each of the plurality of columns connecting the plurality of first channels to the respective plurality of second channels to form a plurality of independent paths; Includes one of the plurality of first channels, one of the respective plurality of second channels, and one of the respective plurality of columns, wherein the plurality of columns Microfluidic devices where the independent paths are parallel to each other. The microfluidic device of claim 1, further comprising an input opening in fluid communication with the first channel. The microfluidic device of claim 1, wherein the filter frit material comprises a body, a gel chamber disposed in the body, and an opening in the body in fluid communication with the gel chamber; wherein the filter A microfluidic device in which frit material is disposed in the column and the opening faces toward the first channel. A method of manufacturing a microfluidic device according to claim 4, wherein the method comprises the following steps:
Pushing the filter frit material into the column; and applying the first cover to the first surface, wherein the first cover covers the filter frit material;
Including the method. Built-in gel filtration frit with the following:
A body comprising a form-stable filter frit material;
A chamber formed in the body; and a gel filtration material disposed in the chamber;
Embedded gel filtration frit. 14. The built-in gel filtration frit of claim 13, further comprising an opening in the body in fluid communication with the gel chamber. 14. The built-in gel filtration frit of claim 13, wherein the gel filtration material comprises an ion exchange material. 14. The built-in gel filtration frit of claim 13, wherein the form-stable filter frit material comprises a hydrophilic polyethylene material. 14. The built-in gel filtration frit of claim 13, wherein the body has a rectangular-like shape. 14. The embedded gel filtration frit of claim 13, wherein the embedded gel filtration frit has a length dimension, a width dimension, and a depth dimension, each of which is less than 50 mm. . 14. The built-in gel filtration frit of claim 13, wherein the chamber has a rectangular-like shape or a cylindrical shape. 14. The built-in gel filtration frit of claim 13, wherein the body has a rectangular-like shape or a cylindrical shape. 21. The built-in gel filtration frit of claim 20, wherein the body comprises an opening in fluid communication with the chamber. A microfluidic device comprising:
A first surface, a second surface opposite the first surface, and a substrate having a thickness;
14. A channel formed in the substrate and having an input opening and a discharge opening; and the embedded gel filtration frit of claim 13 disposed in the channel;
A microfluidic device comprising: A microfluidic device comprising:
A substrate having a first surface, a second surface opposite the first surface, and a thickness;
A channel formed in the substrate and having an inlet opening and an outlet opening; and the embedded gel filtration frit of claim 14 disposed in the channel;
With
Wherein the input opening of the channel is in fluid communication with the opening of the built-in gel filtration frit;
Microfluidic device. A microfluidic device comprising:
A substrate having a first surface, a second surface opposite the first surface, and a thickness;
A channel in the first surface having a first depth extending perpendicular to the first surface and in a direction toward the second surface, and complementary to the channel; The built-in gel filtration frit of claim 14, having a shape.
With
Wherein the opening of the built-in gel filtration frit faces the input opening of the channel and is in flow library communication with the input opening of the channel;
Microfluidic device. A microfluidic device comprising:
A substrate having a first surface, a second surface opposite the first surface, and a thickness;
A first channel formed in the substrate and extending in a first direction, the first channel having a first cross-sectional area defined by at least a first minimum dimension and a first depth. A first channel having a first depth extending in a direction perpendicular to the first surface and toward the second surface;
A second channel formed in the substrate and extending in a second direction, the second channel having a second cross-sectional area defined by at least a second minimum dimension and a second depth. A second channel having a second depth extending in a direction perpendicular to the first surface and toward the second surface;
A fluid communication formed between the first channel and the second channel in the substrate and having a third cross-sectional area defined by at least a third minimum dimension, wherein A third cross-sectional area that is smaller than the first cross-sectional area, fluid communication; and a particulate flow restricting material disposed in the first channel and comprising flow restricting particles, wherein the flow restricting particles A particulate flow restricting material comprising at least 10% by weight of flow restricting particles having a particle size smaller than the third smallest dimension;
A microfluidic device comprising: 26. The microfluidic device of claim 25, wherein the first direction and the second direction are aligned with each other in the fluid communication. 26. The microfluidic device of claim 25, wherein at least one of the first channel and the second channel comprises a round cross section. 26. The microfluidic device of claim 25, wherein at least 50% by weight of the flow restricting particles comprise flow restricting particles having a particle size that is less than the third smallest dimension. 26. The microfluidic device of claim 25, wherein at least 95% by weight of the flow restricting particles comprise flow restricting particles having a particle size that is less than the third smallest dimension. 26. The microfluidic device of claim 25, wherein the flow restricting particles have a particle size that is smaller than the second minimum dimension. 26. The microfluidic device of claim 25, wherein the flow restricting material includes a gel filtration material disposed in the first channel, the gel filtration material having an average diameter less than the third cross-sectional area. A microfluidic device having a cross-sectional area. 26. The microfluidic device of claim 25, wherein the mean diameter cross-sectional area of the flow restricting particles is about 0.1 to about 0.2 times the third cross-sectional area. 26. The microfluidic device of claim 25, comprising a stack of flow restricting particles in the fluid communication. 26. The microfluidic device of claim 25, wherein the flow restricting material is:
A first flow restricting material having particles of a first average diameter packed together in the fluid communication; and a first flow restricting material packed together in the first channel and filled together A second flow restricting material having a second average diameter particle adjacent to
Here, the average diameter of the first flow restricting material particles is greater than the average diameter of the second flow restricting material particles, and the second co-filled flow restricting material is More spaced apart from the second channel than one flow restricting material;
Microfluidic device. 26. The microfluidic device of claim 25, further comprising a second material disposed in at least one of the first and second channels, and comprising a particle that hybridizes with a nucleic acid sequence. Fluid device. 26. The microfluidic device of claim 25, wherein the fluid communication includes a tapered transmission region from the first channel to the second channel. 37. The microfluidic device of claim 36, wherein the tapered transmission region has a conical shape. 26. The microfluidic device of claim 25, wherein the microfluidic device contacts the first surface of the substrate and covers at least one of the first channel, the second channel, and the fluid communication. The microfluidic device further comprising a first cover. A microfluidic device comprising:
Base material;
A first channel formed in the substrate; and a first chamber formed in the substrate, the first chamber having a depth and a cross section perpendicular to the depth. The first chamber has a substantially circular first end and a narrower and opposite second end, wherein the first chamber has a teardrop-shaped cross-sectional area. The second end of the first chamber is in fluid communication with the first channel;
A microfluidic device comprising: 40. The microfluidic device of claim 39, wherein the teardrop shaped chamber has a constant cross-sectional area along the depth of the chamber. 40. The microfluidic device of claim 39, further comprising a second chamber formed in the substrate, the second chamber having a depth and a cross section perpendicular to the second depth. The second chamber has a substantially circular first end and a narrower and opposite second end, wherein the second chamber has a teardrop-shaped cross-sectional area, wherein The microfluidic device, wherein the second end of the second chamber is in fluid communication with the first channel. A method of manipulating a liquid comprising the following steps:
40. Providing the microfluidic device of claim 39;
Loading the liquid into a first chamber; and rotating the device about an axis of rotation to impart centripetal force to the liquid from the first chamber to a first channel;
Including the method. A method of manipulating a liquid comprising the following steps:
40. Providing the device of claim 39;
Loading a liquid into the first channel;
Rotating the device about an axis of rotation to impart centripetal force to the liquid from the first channel to the first chamber;
Including the method. A microfluidic device comprising:
A first surface, a second surface opposite the first surface, and a substrate having a thickness;
A plurality of parallel paths formed in the substrate, each of the paths being
Input opening,
Discharge opening,
At least one processing chamber positioned between the input opening and the discharge opening, wherein the input opening, the at least one processing chamber, and the discharge opening are arranged in a plurality of parallel; Navigable route;
A first fluid communication between the input opening and the at least one processing chamber; and a second fluid communication between the at least one processing chamber and the discharge opening;
A plurality of parallel paths comprising:
With
Wherein each of the plurality of paths comprises at least one valve that can be opened to form fluid communication;
Microfluidic device. 45. The microfluidic device of claim 44, wherein at least one of the first and second fluid communication comprises a channel formed in the first surface; and the first and second The microfluidic device, wherein the other of the fluid communication comprises a channel formed in the second surface. 45. The microfluidic device of claim 44, wherein the at least one valve includes a first deformable material having a first elasticity, wherein the second deformable material is the first elasticity. A microfluidic device having a different second elasticity. 47. The microfluidic device of claim 46, further comprising a first cover in contact with the first surface of the substrate, wherein the first cover is the second deformable. A microfluidic device that is a material. 45. The microfluidic device of claim 44, further comprising a size exclusion filtration material disposed in the at least one processing chamber. 45. The microfluidic device of claim 44, further comprising a component for enabling a polymerase chain reaction of a nucleic acid sequence disposed in at least one processing chamber. 45. The microfluidic device of claim 44, wherein the at least one processing chamber is shaped as a channel in the first surface of the substrate. 45. The microfluidic device of claim 44, wherein the substrate is rectangular. 45. The microfluidic device of claim 44, wherein the first channel and the first chamber are part of a first path that is at least partially formed in the substrate. Comprises a plurality of paths, each path having a respective channel and a respective chamber, and the respective chambers are each sectioned at a respective depth and perpendicular to the depth. The respective chambers each having a substantially circular first end and a narrower and opposite second end, wherein each chamber has a teardrop-shaped cross-sectional area. The microfluidic device wherein the first end of the is in fluid communication with the respective channel. 53. The microfluidic device according to claim 52, wherein the paths of the plurality of paths are parallel to each other. A microfluidic device comprising:
A first surface, a second surface opposite the first surface, and a substrate having a thickness; and a plurality of parallel paths formed in the substrate, each of the paths being an input opening Fluid communication between the discharge opening, the at least one processing chamber between the input opening and the discharge opening, and the at least one processing chamber and at least one of the input opening and the discharge opening Or at least one valve for providing,
A microfluidic device comprising: 55. The microfluidic device of claim 54, wherein the at least one valve is:
A first recess formed in the substrate;
A second recess formed in the substrate;
An intermediate wall sandwiched between the first recess and the second recess, wherein the intermediate wall portion is formed from a deformable material having a first elasticity;
An elastically deformable cover layer covering the first recess and having a second elasticity greater than the first elasticity, wherein the elastically deformable covered layer comprises: The intermediate wall is in contact with the intermediate wall when in the undeformed state, and the elastically deformable cover layer is not in contact with the intermediate wall when the intermediate wall is in the deformed state, thereby An elastically deformable cover layer that forms fluid communication between the first recess and the second recess;
A microfluidic device comprising: 55. The microfluidic device of claim 54, wherein each valve is:
A first recess formed in the substrate, the first recess comprising a first recess portion and a second recess portion, wherein the first recess is at least partially defined by an opposing wall surface portion At least one of the opposing wall surface portions includes a first deformable material having a first elasticity and an elastically deformable covered layer, wherein the first The recessed portion and the second recessed portion are in fluid communication with each other when the first deformable material is in an undeformed state; the elastically deformable covered layer comprises the The opposing wall surface portion having a second elasticity greater than the first elasticity and covering at least the first recessed portion where the first deformable material includes the barrier wall is in a deformed state A barrier sandwiched between the first recess portion and the second recess portion To form a deformable so as to prevent fluid communication between the recess portion and the second recess portion of the first, the first recess,
Comprising
Microfluidic device. A sample processing system that:
A microfluidic device comprising:
A substrate comprising a first surface, a second surface opposite the first surface, and a thickness;
A plurality of parallel paths formed in the base material, each of the paths being between the input opening, the discharge opening, and the input opening and the discharge opening, the input opening and the discharge opening being a fluid A microfluidic device comprising at least one processing chamber in communication;
A platen comprising a holder capable of holding the microfluidic device and having a rotational axis, the holder being spaced apart from the rotational axis and disposed off-center with respect to the rotational axis , Platen;
A drive unit for rotating the platen about the rotation axis; and a control unit for controlling the drive unit;
A sample processing system comprising: 58. The system according to claim 57, wherein the microfluidic device is disposed in the holder, and each input opening of the plurality of paths is closer to the rotation axis than each discharge opening of the plurality of paths. ,system. 58. The sample processing system of claim 57, wherein each of the plurality of parallel paths comprises a respective input opening, processing chamber, and discharge opening in a linear arrangement. 58. The sample processing system of claim 57, wherein:
Heating the at least one processing chamber of a device disposed in the holder; a heating element; and a heating control unit controlling the heating element;
A sample processing system further comprising: 58. The sample processing system of claim 57, wherein the microfluidic device is:
At least one valve in each of the plurality of paths, each valve blocking or providing fluid communication between the at least one processing chamber and at least one of the input opening and the discharge opening. Valves, which are for
A sample processing system further comprising: 58. The sample processing system of claim 57, wherein the platen comprises a plurality of holders, each holder capable of holding the microfluidic device. 58. The sample processing system of claim 57, wherein the microfluidic device is shaped as a rectangle having a length, a width, and a thickness, and the holder is configured so that any of the plurality of paths is on the rotation axis. A sample processing system that is capable of holding the microfluidic device so that it is not radially aligned with respect to. 58. The sample processing system of claim 57, wherein the microfluidic device has opposing first and second rectangular surfaces, each of which has a length greater than its width. A sample processing system. 65. A sample processing system according to claim 64, wherein the microfluidic device is disposed in the holder and the radius of the platen is perpendicular to the length of the microfluidic device. 65. A sample processing system according to claim 64, wherein the microfluidic device is disposed in the holder and the radius of the platen is perpendicular to the width of the microfluidic device. 58. The sample processing system of claim 57, wherein:
A sample processing system further comprising: a heating element disposed at a position capable of heating the at least one processing chamber relative to the platen; and a heating control unit that controls the heating requirements. A sample processing method comprising the following steps:
58. Providing a sample processing system according to claim 57;
Introducing a sample into at least one of the input openings of the plurality of paths;
Placing the microfluidic device in the holder; and rotating the platen to move the sample;
Including the method. A method of fabricating a microfluidic device, the method comprising the following steps:
A substrate, an input opening formed in the substrate, a first channel formed in the substrate and in fluid communication with the input opening, a second channel formed in the substrate, and the Providing a microfluidic device comprising fluid communication between the first channel and the second channel;
Introducing a gel filtration material into the first channel through the input opening; and filling the gel filtration material in the fluid communication and passing a substantial portion of the gel filtration material through the fluid communication. Applying a centripetal force to the device that prevents it from moving into the second channel;
Including the method. A microfluidic device comprising:
Base material;
A first recess formed in the substrate;
A second recess formed in the substrate;
An intermediate wall sandwiched between the first recess and the second recess, wherein the intermediate wall portion is formed from a deformable material having a first elasticity;
An elastically deformable covered layer covering the first recess and having a second elasticity greater than the elasticity of the first elasticity, wherein the elastically deformable covered layer Is in contact with the intermediate wall when the intermediate wall is in an undeformed state, and the elastically deformable covered layer is in contact with the intermediate wall when the intermediate wall is in a deformed state. An elastically deformable covered layer without forming a fluid communication between the first recess and the second recess; and a granular flow restriction disposed in the first recess material,
A microfluidic device comprising: 71. A system comprising a microfluidic device, a deforming blade, and a positioning unit according to claim 70, wherein the positioning unit causes the deforming blade to contact the microfluidic device so that the blade deforms the intermediate wall. A flow restricting channel may be formed between the first recess and the second recess, the first recess having a first cross-sectional area defined by at least a first minimum dimension; The flow restricting channel has a second cross-sectional area defined by at least a second minimum dimension, wherein the first recess and the flow restricting channel intersect each other in fluid communication and the fluid communication Has a third cross-sectional area defined by at least a third minimum dimension, wherein the third cross-sectional area is smaller than the first cross-sectional area and the particulate flow restricting material is flow restricting particle Wherein at least 10 wt.% Of the flowable restrictions particles comprise particles having a particle size smaller than the minimum dimension of the third system. A sample processing assembly comprising a sample processing device, the sample processing device comprising: a body comprising a first side attached to a second side; between the first side and the second side A plurality of formed process arrays, wherein each process array of the plurality of process arrays includes a plurality of process arrays comprising a loading structure, a main conduit having a length, and a distribution along the main conduit And a deformable seal positioned between the loading structure and the plurality of process chambers, wherein the main conduit includes the loading structure and the plurality of process chambers and fluids A plurality of process arrays in communication; a carrier attached to the sample processing device, the carrier comprising the sample processing device; A carrier comprising a first surface facing the device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximal to the first surface of the carrier Wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and the first surface of the carrier and A sample processing assembly, wherein a plurality of openings are formed through the second surface, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. 73. The assembly of claim 72, wherein the carrier further comprises a plurality of compression structures proximate the first surface of the carrier, each compression structure of the plurality of compression structures comprising: An assembly proximal to one of the plurality of process chambers. 75. The assembly of claim 72, wherein the carrier is a plurality of compression structures proximate the first surface of the carrier, each compression structure of the plurality of compression structures comprising: A compression structure proximate to one of the plurality of process chambers; and a plurality of force transmission structures, each force transmission structure of the plurality of force transmission structures comprising the carrier A separate joint region proximal to the second surface of the plurality of force transmission structures, wherein each force transmission structure of the plurality of force transmission structures is operably connected to a plurality of the plurality of compression structures, A force transmission structure, wherein force applied to the joint surface of each force transmission structure is transmitted to the plurality of compression structures operably connected to the force transmission structure. . 75. The assembly of claim 72, wherein the carrier further comprises a plurality of collars proximal to the first surface of the carrier, each color of the plurality of colors comprising the plurality of processes. An assembly aligned with and proximal to one of the chambers. 75. The assembly of claim 72, further comprising a plurality of collars proximal to the first surface of the carrier, wherein each opening of the plurality of openings is of the plurality of collars. An assembly wherein each color of the plurality of colors is aligned with a process chamber of the plurality of process chambers. A method of processing a sample material, the method comprising the following steps:
A body comprising a first side attached to a second side; a plurality of process arrays formed between the first side and the second side, wherein the plurality of process arrays Each process array includes a loading structure, a main conduit having a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit includes the loading structure and the plurality of processes. A plurality of process arrays in fluid communication with the chamber; a deformable seal positioned between the loading structure and the plurality of process chambers in each process array of the plurality of process arrays; An attached carrier, the carrier being a first surface facing the sample processing device and remote from the sample processing device And a plurality of main conduit support rails proximate to the first surface of the carrier, wherein each main conduit of the plurality of process arrays includes the plurality of main conduits A main conduit support rail aligned with one of the main conduit support rails; a plurality of openings formed through the first surface and the second surface of the carrier; A sample processing device comprising: a plurality of openings, wherein each opening of the plurality of openings is aligned with a process chamber of the plurality of process chambers;
Providing a sample processing assembly comprising:
Distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays;
Closing the deformable seal in each process array of the plurality of process arrays, the closing step supporting the main conduit with one of the main conduit support rails and simultaneously Compressing the first side and the second side together along the main conduit;
Positioning the second side of the sample processing device in contact with a thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block;
Including the method. 78. The method of claim 77, wherein closing the deformable seal in each process array of the plurality of process arrays includes simultaneously closing the deformable seal in each process array of the plurality of process arrays. how to. 78. The method of claim 77, wherein for each process array of the plurality of process arrays, closing the deformable seal comprises deforming a deformable portion of the second side of the body. The method of inclusion. A method of processing a sample material, the method comprising the following steps:
A body having a first side attached to a second side; a plurality of process arrays formed between the first side and the second side, wherein the plurality of process arrays Each process array includes a loading structure, a main conduit having a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit includes the loading structure and the plurality of process chambers. A plurality of process arrays in fluid communication with the carrier; a carrier attached to the sample processing device, the carrier facing the first surface facing the sample processing device and the surface remote from the sample processing device A carrier comprising: a second surface; a plurality of apertures formed through the first surface and the second surface of the carrier, wherein the plurality of apertures Each opening is aligned with one process chamber of the process chambers of the plurality, and a sample processing device comprising a plurality of apertures, providing a sample processing assembly;
Distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays;
Positioning the second side of the sample processing device in contact with a heat block;
Selectively compressing the first side and the second side of the sample processing device with each process chamber proximal to the plurality of process chambers, the selective compression comprising the carrier and the Taking place between the thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block;
Including the method. 81. The method of claim 80, wherein the carrier comprises a compressible material, and the selectively compressing comprises compressing substantially all of the sample processing device from outside the process chamber. Including the method. 81. The method of claim 80, wherein the carrier further comprises a plurality of compression structures proximate the first surface of the carrier, each compression structure of the plurality of compression structures comprising: Proximal to one process chamber of the plurality of process chambers, and the selectively compressing step is separate using the compression structure and proximal to each of the process chambers. Compressing the region of the method. A sample processing assembly comprising a sample processing device, the sample processing assembly comprising: a body comprising a first side attached to a second side; and the first side and the second side A plurality of process arrays formed therebetween, wherein each process array of the plurality of process arrays includes a loading structure, a main conduit having a length, and a plurality of processes distributed along the main conduit A chamber, wherein the main conduit comprises a plurality of process arrays in fluid communication with the loading structure and the plurality of process chambers; and a carrier attached to the sample processing device, the carrier comprising: A plurality of profiles comprising a first surface facing the sample processing device and a second surface facing away from the sample processing device. A plurality of openings formed through the first surface and the second surface of the carrier, wherein each opening of the plurality of openings is a process of the plurality of process chambers; A plurality of compression structures proximate to the first surface of the carrier, wherein each compression structure of the plurality of compression structures includes the plurality of process chambers; A sample processing assembly comprising a plurality of compression structures proximal to one of the process chambers. 84. The assembly of claim 83, wherein each of the compression structures comprises a collar aligned with one of the process chambers. A sample processing assembly comprising a sample processing device, the sample processing device comprising a body comprising a first side attached to a second side; and between the first side and the second side A plurality of formed process arrays, wherein each process array of the plurality of process arrays includes a loading structure, a main conduit having a length, and a plurality of process chambers distributed along the main conduit. A plurality of process arrays in fluid communication with the loading structure and the plurality of process chambers; and a plurality of process arrays in each process array of the plurality of process arrays. A deformable seal located between the process chamber; and a carrier attached to the sample processing device; A body having a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit supports proximal to the first surface of the carrier A plurality of main conduit support rails, wherein each main conduit of the plurality of process arrays is aligned with a main conduit support rail of one of the plurality of main conduit support rails; A plurality of openings formed through the first surface and the second surface of the plurality of openings, wherein each opening of the plurality of openings is aligned with a process chamber of the plurality of process chambers. A plurality of apertures; a plurality of compression structures proximate to the first surface of the carrier, each compression structure of the plurality of compression structures comprising the plurality of processes Process chamber in one of the chambers Is proximal to Nba, and a plurality of compression structures, sample processing assembly. 89. The assembly of claim 85, wherein each of the compression structures comprises a collar aligned with one of the process chambers. A method of processing a sample material, the method comprising the following steps:
A body comprising a first side attached to a second side; a plurality of process arrays formed between the first side and the second side, wherein the plurality of process arrays Each process array includes a loading structure, a main conduit having a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit includes the loading structure and the plurality of processes. A plurality of process arrays in fluid communication with the chamber; the loading structure; and a deformable seal positioned between the plurality of process chambers in each process array of the plurality of process arrays; A carrier attached to the first surface facing the sample processing device and remote from the sample processing device A carrier comprising a second surface facing; a plurality of main conduit support rails proximal to the first surface of the carrier, wherein each main conduit of the plurality of process arrays comprises: A plurality of main conduit support rails aligned with a main conduit support rail of the plurality of main conduit support rails; a plurality of formed through the first surface and the second surface of the carrier Providing a sample processing assembly comprising a sample processing device, wherein each opening of the plurality of openings has a plurality of openings aligned with a process chamber of the plurality of process chambers. The step of:
Distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays;
Closing the deformable seal in each process array of the plurality of process arrays, the closing step connecting the first side and the second side of the sample processing device to the length of the main conduit. Supporting the main conduit with at least one of the main conduit support rails while compressing together along at least a portion;
Positioning the second side of the sample processing device in contact with a heat block;
Selectively compressing the first side and the second side of the sample processing device with each process chamber proximal to the plurality of process chambers, the selective compression comprising the carrier and the Taking place between the thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block;
Including the method. 90. The method of claim 87, wherein the selectively compressing comprises compressing substantially all of the sample processing device from outside the process chamber. 90. The method of claim 87, wherein the carrier comprises a compressible material, and wherein the selectively compressing comprises compressing substantially all of the sample processing device from outside the process chamber. Including the method. 90. The method of claim 87, wherein the selectively compressing comprises compressing a separate region proximal to each of the process chambers. 90. The method of claim 87, wherein the carrier further comprises a plurality of collars proximal to the first surface of the carrier, each color of the plurality of colors comprising the plurality of processes. In addition to the one of the plurality of collars; wherein the selectively compressing step separates a separate region proximal to each of the process chambers into one of the plurality of collars. A method comprising the step of compressing in color. A method of processing a sample material, the method comprising the following steps:
A body comprising a first side attached to a second side; a plurality of process arrays formed between the first side and the second side, wherein the plurality of process arrays Each process array includes a loading structure, a main conduit having a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit includes the loading structure and the plurality of processes. A plurality of process arrays in fluid communication with the chamber; the loading structure; and a deformable seal positioned between the plurality of process chambers in each process array of the plurality of process arrays; And a carrier attached to the first surface facing the sample processing device and remote from the sample processing device A second surface facing; a plurality of main conduit support rails proximal to the first surface of the carrier, wherein each main conduit of the plurality of process arrays includes the plurality of main conduits; A plurality of main conduit support rails aligned with one of the conduit support rails; a plurality of openings formed through the first surface and the second surface of the carrier; Providing a sample processing assembly comprising a sample processing device, wherein each opening of the plurality of openings comprises a plurality of openings aligned with a process chamber of the plurality of process chambers;
Distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays;
Closing the deformable seal in each process array of the plurality of process arrays, the closing step connecting the first side and the second side of the sample processing device to the length of the main conduit. Supporting the main conduit with one of the main conduit support rails while compressing together along at least a portion;
Separating the loading structure of each process array of the plurality of process arrays from the sample processing device;
Positioning the second side of the sample processing device in contact with a heat block;
Controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block;
Including the method. A method of processing a sample material, the method comprising the following steps:
A body comprising a first side attached to a second side; a plurality of process arrays formed between the first side and the second side, wherein the plurality of process arrays Each process array includes a loading chamber, a main conduit having a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit includes the loading chamber and the plurality of process chambers. A plurality of process arrays in fluid communication; and the deformable seal positioned between the loading chamber and the plurality of process chambers in each process array of the plurality of process arrays; and attached to the sample processing device A first surface facing the sample processing device and the sample processing device. A second surface facing away; a plurality of main conduit support rails proximal to the first surface of the carrier, wherein each main conduit of the plurality of process arrays includes the plurality of main conduits; A plurality of main conduit support rails aligned with one of the main conduit support rails; a plurality of openings formed through the first surface and the second surface of the carrier Wherein each opening of the plurality of openings provides a sample processing assembly comprising a sample processing device comprising a plurality of openings aligned with a process chamber of the plurality of process chambers. Process;
Distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays;
Closing the deformable seal in each process array of the plurality of process arrays, the closing step connecting the first side and the second side of the sample processing device to the length of the main conduit. Supporting the main conduit with one of the main conduit support rails while compressing together along at least a portion;
Separating the loading chamber of each process array of the plurality of process arrays from the sample processing device;
Selectively compressing the first side and the second side of the sample processing device with each process chamber proximal to the plurality of process chambers, the selective compression comprising: Steps occurring between the support and the heat block;
Positioning the second side of the sample processing device in contact with a thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block;
Including the method. 94. The method of claim 93, wherein the selectively compressing comprises compressing substantially all of the sample processing device from outside the process chamber. 94. The method of claim 93, wherein the selectively compressing comprises compressing a separate region proximal to each of the process chambers. A sample processing system, comprising: a body having a first side attached to a second side; and a plurality of process arrays formed between the first side and the second side Wherein each process array of the plurality of process arrays comprises a loading structure, a main conduit comprising a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit comprises: A plurality of process arrays in fluid communication with the loading structure and the plurality of process chambers; a thermal block in which the sample processing device is located; the first side and the second side of the sample processing device For each process chamber of the plurality of process chambers after positioning the second side of the sample processing device in contact with a heat block Sample processing system comprising both means for simultaneously and selectively compressed in a separate area at the position, the sample processing device comprising a. 99. The system of claim 96, wherein each process array of the plurality of process arrays comprises a deformable seal positioned between the loading structure and the plurality of process chambers.

Images