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WO2004011365A2 - Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete - Google Patents

Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete Download PDF

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Publication number
WO2004011365A2
WO2004011365A2 PCT/US2003/022226 US0322226W WO2004011365A2 WO 2004011365 A2 WO2004011365 A2 WO 2004011365A2 US 0322226 W US0322226 W US 0322226W WO 2004011365 A2 WO2004011365 A2 WO 2004011365A2
Authority
WO
WIPO (PCT)
Prior art keywords
microfluidic device
branch channels
substrate
platen
parallel
Prior art date
Application number
PCT/US2003/022226
Other languages
English (en)
Other versions
WO2004011365A3 (fr
Inventor
Sean M. Desmond
John Shigeura
Original Assignee
Applera Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US10/336,274 external-priority patent/US7198759B2/en
Priority claimed from US10/336,706 external-priority patent/US7214348B2/en
Application filed by Applera Corporation filed Critical Applera Corporation
Priority to JP2005505600A priority Critical patent/JP2005533651A/ja
Priority to EP03771636A priority patent/EP1534429A4/fr
Priority to AU2003253944A priority patent/AU2003253944A1/en
Priority to CA002493700A priority patent/CA2493700A1/fr
Publication of WO2004011365A2 publication Critical patent/WO2004011365A2/fr
Publication of WO2004011365A3 publication Critical patent/WO2004011365A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces

Definitions

  • the present application relates to microfluidic devices, systems that include such devices, and methods that use such devices and systems. More particularly, the present application relates to devices that manipulate, process, or otherwise alter micro- sized amounts of fluids and fluid samples.
  • Microfluidic devices are used for manipulating fluid samples. There continues to exist a demand for microfluidic devices, methods of using them, and systems incorporating them for processing samples that are fast, reliable, consumable, and can be used to process large number of samples simultaneously.
  • a microfluidic device having a flow channel and including an excess fluid capture reservoir.
  • the device can provide a metered quantity of sample for processing and capture all excess sample.
  • a microfluidic device is provided having a substrate having a first surface, an opposite second surface, and a thickness, an input port formed in at least one of the first and second surfaces, and a manifold formed in the substrate and in fluid communication with the input port, the manifold including a feed channel that extends in a first direction, and a plurality of branch channels each branching off the feed channel and each terminating at a closed end.
  • the branch channels can be parallel to one another.
  • a sample processing system having a microfluidic device and a processing apparatus.
  • the microfluidic device includes a substrate having a first surface, an opposite second surface, and a thickness, an input port formed in at least one of the first and second surfaces, and a manifold.
  • the manifold can be formed in the substrate and in fluid communication with the input port, and can include a feed channel that extends in a first direction, and a plurality of parallel branch channels branching off the feed channel.
  • the branch channels can be parallel to one another.
  • the processing apparatus can include a rotatable platen having an axis of rotation, a holder capable of holding a microfluidic device on or in the platen and being disposed off-center with respect to the axis of rotation, and a drive unit to rotate the platen about the axis of rotation.
  • a sample processing system having a microfluidic device and a processing apparatus.
  • the microfluidic device can include a substrate having a first substantially rectangular surface, a second substantially rectangular surface opposite the first surface, a thickness, a length, a width, and a plurality of geometrically parallel processing pathways arranged parallel to either the length or the width of the substrate.
  • the processing apparatus can include a rotatable platen having an axis of rotation, and a holder capable of holding the microfluidic device on or in the platen and disposed off-center with respect to the axis of rotation.
  • the holder can be capable of holding the microfluidic device in or on the platen such that any radius of the platen that is parallel to the length or the width of the microfluidic device does not intersect the other of the width or the length, respectively, of the microfluidic device.
  • a method of distributing a liquid sample into a plurality of branch channels in a microfluidic device can include providing a microfluidic device, introducing a liquid sample through an input port and into a feed channel of the device, and centrifugally spinning the microfluidic device to force fluid from the feed channel into the branch channels.
  • the microfluidic device can include a substrate, an input port, and a manifold, wherein the substrate includes a first surface, an opposite second surface, and a thickness, the input port is formed in at least one of the first and second surfaces, and the manifold is formed in the substrate in fluid communication with the input port.
  • the manifold can include the feed channel that extends in a first direction, and a plurality of branch channels each branching off the feed channel normal to the feed channel.
  • the branch channels can be parallel to one another.
  • FIG. 1 is a top view of a microfluidic device having a fluid capture appendix
  • FIG. 2 is a top view of a microfluidic device having a manifold having a feed channel and a plurality of parallel branch channels;
  • FIG. 3 is a top view of a microfluidic device having a flow splitter
  • FIG. 4 is a side view of a microfluidic device having a flow splitter in the depth profile of a substrate
  • Figs. 5a-5d are cross-sectional views of microfluidic channels having various profiles in the substrate
  • Fig. 6a is a top view of a microfluidic device depicting a rectangular substrate oriented to allow fluid movement across the length of the substrate;
  • Fig. 6b is a top view of a microfluidic device depicting a rectangular substrate oriented to allow fluid movement across the width of the rectangular substrate;
  • Fig. 6c is a top view of a platen holding two microfluidic devices each including a rectangular substrate;
  • Fig. 7a is a top view of a microfluidic device having teardrop-shaped input ports oriented such that, when the microfluidic device is held on and spun by a rotatable platen, the narrow end of the teardrop-shaped input ports is radially further away from an axis of rotation than the circular end of the teardrop-shaped input port;
  • Fig. 7b is an enlarged portion of Fig. 7a taken along dashed line 7b, shown in Fig.
  • FIGs. 8 is a diagram of a microfluidic device having a plurality of input ports capable of distributing a fluid sample to a respective plurality of flow distributors, each flow distribution respectively in fluid communication with a plurality of pathways.
  • a microfluidic device having a flow channel and including an excess fluid capture reservoir.
  • the device can provide a metered quantity of sample for processing and capture all excess sample.
  • Fig. 1 is a top view of a microfluidic device 140 that can be used, for example, to capture an excess fluid sample which can be retained after sample processing, for example, after PCR amplification
  • Microfluidic device 140 includes a substrate 142 having an input port 106 and an input channel 144.
  • Input channel 144 connects to a feed channel 150 that is divided into two parallel branch channels 146 and 148 of unequal volume.
  • Parallel branch channel 148 can be used as an excess fluid capture reservoir appendix.
  • Input channel 144 is upstream of parallel branch channels 146 and 148. Upstream of input channel 144 can be an input port 106 as shown, or a chamber, well, or opening.
  • the parallel branch channel 148 is designed as an appendix and is not in any further fluid communication with any other chambers, the parallel branch channel 146 can be in fluid communication with other chambers, wells, or openings further downstream, or can be made to be in fluid communication as by valving.
  • a PCR reaction can be performed, for example, in a 5 ⁇ L volume, wherein a 2 ⁇ L volume can be required for the sequencing reaction, and a remaining 3 ⁇ L volume can be used for diagnostics.
  • a user can analyze this excess diagnostic material on an agarose gel to verify that fragments are being properly amplified.
  • parallel branch channel 148 can be used as a fluid capture appendix.
  • Branch channel 146 can contain 2 ⁇ L of sample 154 while an excess 3 ⁇ L of sample 156 can be contained in parallel branch channel 148.
  • a valve can be opened after distribution of the sample into the parallel branch channels, and the 2 ⁇ L sample 154 can flow to a subsequent reaction chamber, for example, an EXO-SAP chamber, while the excess sample 156 remains in branch channel 148.
  • the excess sample 156 can be accessed by piercing a cover 152 of the device with a needle, syringe, or pipette, and carefully extracting a desired amount of sample 156 from branch channel 148.
  • a microfluidic device having a substrate having a first surface, an opposite second surface, and a thickness, an input port formed in at least one of the first and second surfaces, and a manifold formed in the substrate and in fluid communication with the input port.
  • the manifold can include a feed channel that extends in a first direction, and a plurality of branch channels each branching off the feed channel and each terminating at a closed end.
  • the branch channels can be parallel to one another.
  • the substrate can also include a plurality of respective chambers, at least one chamber formed in the substrate adjacent the closed end of each branch channel. Each of the plurality of branch channels can extend in a direction normal to the feed channel.
  • Each of the plurality of branch channels can be in interruptible fluid communication with a respective pathway having at least one processing chamber.
  • a valve can be provided between each of the branch channels and its respective at least one processing chamber.
  • Each of the plurality of branch channels can have a valve.
  • the manifold can contain a first volume of fluid, about equal to the collective volume of the plurality of branch channel volumes.
  • each of the plurality of branch channels in the microfluidic device extends in a direction that can be parallel to and/or normal to the first surface of the substrate in the microfluidic device. [00024]
  • each of the plurality of branch channels has a volume.
  • the collective volume of the plurality of branch channels in the microfluidic device can be from about 5 ⁇ l to about 100 ⁇ l, for example, about 50 ⁇ l.
  • the volume of each parallel branch channel can be from about 0.05 ⁇ l to about 5 ⁇ l, for example, 0.5 ⁇ l, 1 ⁇ l, or 2 ⁇ l.
  • the input port of the microfluidic device can be teardrop-shaped, having a wide end and a narrow end, wherein the narrow end is in fluid communication with the feed channel.
  • Fig. 2 is a top view of a microfluidic device 100.
  • Microfluidic device 100 can be formed in a substrate 108.
  • Microfluidic device 100 can include an input port 106 in fluid communication with an input channel 104 connected to a feed channel 110.
  • a plurality of parallel branch channels 102 can connect to feed channel 110.
  • Microfluidic device 100 can in this configuration be used as a flow distributor.
  • Microfluidic device 100 can be used to split a single fluid sample into a plurality of sub-portions. Similar microfluidic devices but used to divide a sample into only two portions are referred to herein as flow splitters.
  • microfluidic device 100 can be placed on a rotatable platen (not shown) and the platen can be spun.
  • Substrate 108 can be oriented in a holder in, on or for the platen such that input channel 104 can be radially closer to the center of the platen than the plurality of parallel branch channels.
  • input channel 104 can be disposed in substrate 108 such that input channel 104 connects to feed channel 110 at a radially measured point along feed channel 110 closest to the center of the platen and centrifugation provides a plurality of aliquots or sample portions 112.
  • fluid distributors for splitting the fluid sample from one sample into 2 or more samples or aliquots can be formed, for example, for splitting a sample into 2, 3, 6, 12, 24, 48, 96, 192, or 384 samples or aliquots.
  • Parallel branch channels 102 can be used to obtain equal volumes of fluids in as many portions or aliquots 112 as desired.
  • Parallel branch channels 102 can be in fluid communication with processing chambers (not shown) forming individual pathways for further processing of each aliquot 112.
  • the pathways can be used to perform a single reaction or process, for example, forward sequencing, or can perform multiple same or multiple distinct reactions or processes, for example, PCR, on an aliquot.
  • Reagents needed to perform a certain reaction or process in the processing chamber of a pathway can be loaded in the respective processing chamber at the time of manufacture of the microfluidic device 100, or can be loaded at the time of use.
  • parallel branch channels 102 can have reagents disposed therein such that a reaction can take place in parallel branch channels 102.
  • Reagents can be disposed in the processing chambers using any methods known in the art. For example, reagents can be sprayed and dried, delivered using a diluent, injected using a capillary, a pipette, and/or a robotic pipette, or otherwise disposed in the processing chambers or channels.
  • input channel 104 can connect to feed channel 110 at any point on feed channel 110 that opposes parallel branch channels 102.
  • the connection can be, for example, at a midpoint of feed channel 110 or proximate to an end of feed channel 110.
  • feed channel 110 can be an input port.
  • parallel branch channels 102 do not connect with feed channel 110 at a right angle.
  • fluid communication downstream of parallel branch channels 102 can be interruptible by using a plurality of respective valves (not shown).
  • each parallel branch channel 102 can have a respective valve in fluid communication with the parallel branch channel 102.
  • Microfluidic device 100 can be spun on a platen to deliver a fluid sample from input port 106 to each parallel branch channel 102 before valves in fluid communication with each parallel branch channel 102 are manipulated.
  • a valve does not have to be in fluid communication with one or more of parallel branch channels 102.
  • a fluid sample can be manipulated through feed channel 110 and can fill a first parallel branch channel 102 until overflow from that parallel branch channel 102 flows into the next, adjacent parallel branch channel.
  • Fig. 3 is a top view of a microfluidic device 120 that includes a substrate 128 and a cover layer 121.
  • Input channel 122 under cover layer 121 connects to a manifold including feed channel 126 and a plurality of parallel branch channels 124 in fluid communication with the feed channel 126, all also under cover layer 121.
  • Input channel 122 can connect to feed channel 126 proximate to a mid-point of feed channel 126.
  • Figs. 1-3 depict flow splitters formed in a microfluidic device in a planar format, for example, either in a first surface or a second surface of the substrate. This arrangement is in the horizontal plane and is one possible embodiment for splitting a fluid sample. According to various embodiments, the fluid sample can be split in a vertical plane of the substrate.
  • a flow distributor can be formed within a thickness of a substrate.
  • the flow splitter implemented in the vertical plane can have a closed-end branch channel, an open-end branch channel, or a plurality of open-end and/or close-end branch channels, or a combination thereof.
  • a closed-end branch channel can be an appendix such as a fluid capture appendix.
  • a flow distributor can be right-justified or left-justified with respect to its placement in a holder in a rotatable platen in a direction toward a central axis of rotation of the platen.
  • a right-justified flow distributor has an input channel connected to a right-end of the feed channel.
  • a left-justified flow distributor has an input channel connected to a left-end of the feed channel.
  • a flow distributor can be center-justified, having an input channel connected to a proximate center along the length of the feed channel.
  • FIG. 4 is a side-perspective view of a microfluidic device 160 according to various embodiments.
  • An input channel 172 is in fluid communication with a manifold including feed channel 170.
  • Feed channel 170 is in fluid communication with parallel branch channels 168 and 174 formed in a substrate 162.
  • the microfluidic device further includes a first cover 164 and a second cover 166, for example, made of plastic or metal film or foil.
  • parallel branch channels 168 and 174 are formed in the depth dimension of substrate 162. A volume of sample fluid can be retained in parallel branch channel 168 of microfluidic device 160.
  • the fluid can be transferred to a subsequent channel or chambers after opening a valve (not shown), or stored in parallel branch channel 168 for future analysis.
  • parallel branch channel 168 can be used as an appendix, reservoir, or other device for excess fluid capture.
  • the arrangement of chambers, valves, channels, and vias as described and shown with reference to Fig. 4 is referred to herein as a vertical splitter.
  • microfluidic devices for example, microfluidic devices 100, 120, 140, and 160 described in the various figure herein, can be formed in a rectangular substrate.
  • An input port of the microfluidic device can be a teardrop-shaped chamber.
  • the microfluidic device can be held in or on a platen and rotated around a central axis of rotation of the platen.
  • a rotational force necessary to spin the platen including the microfluidic device can be sufficient to communicate a fluid from an input port of the microfluidic device into a flow distributor, into a flow restrictor, and/or through a valve.
  • a volume of sample fluid captured in an appendix of the microfluidic device can be greater, the same, or less than the volume of fluid in a parallel branch channel.
  • Figs. 5a-5d are cross-sectional views of various channel profiles that can be used in microfluidic devices according to various embodiments.
  • channel 242 is formed with a rectangular cross-sectional area in a substrate 240.
  • the cross-sectional area has an aspect ratio, that is, a width/depth ratio, of greater than one.
  • channel 246 is formed with a semi-oval cross-sectional area in a substrate 244.
  • the cross-sectional area has an aspect ratio, that is, a width/depth ratio, of greater than one.
  • Fig. 5a-5d are cross-sectional views of various channel profiles that can be used in microfluidic devices according to various embodiments.
  • channel 242 is formed with a rectangular cross-sectional area in a substrate 240.
  • the cross-sectional area has an aspect ratio, that is, a width/depth ratio, of greater than one.
  • Fig. 5b channel 246 is formed with a semi-oval cross-sectional area in a substrate 244.
  • a thin and narrow channel 250 is formed in a substrate 248, wherein the cross-sectional area has an aspect ratio, that is, a width/depth ratio, of less than one.
  • a channel 254 is formed with a trapezoidal cross-sectional area in a substrate 252 and generally has an aspect ratio of les than one.
  • the dimensional characteristics of an exemplary straight channel flow restrictor cross-section can be, for example, about 0.2 mm by about 0.2 mm
  • the width of such a channel can be from about 0.05 mm to about 0.5 mm, for example, about 0.2 mm
  • the height of such a channel can be from about 0.05 mm to about 0.5 mm, for example, about 0.2 mm
  • the length of such a channel can be, for example, from about 0.1 mm to about 10 cm, for example, about 5 mm
  • a flow restrictor can be used in conjunction with a larger chamber having a minimum dimension greater than approximately 0.50 mm, and can serve to retain particles in a chamber, for example, P-10 beads available from BioRad, size-exclusion ion- exchange beads, particulates, size-exclusion chromatography beads, other particles known to those skilled in the art, or a combination thereof
  • the flow restrictor can be located downstream of the chamber holding the particles.
  • Downstream means the flow restrictor is located at a greater distance away from the axis of rotation when the device is operably held on a rotatable platen, than the chamber.
  • the fluid sample and the particulates in the chamber can move toward the flow restrictor where the particulates can be retained while the fluids can pass into an adjacent channel or chamber.
  • dimensions of the flow restrictor are not limited to square cross-sections. Other shapes can be successfully implemented. For example, a rectangular flow-restricting channel having a cross-section with about a 0.10 mm depth and about a 0.30 mm width can be formed in a substrate to retain gel filtration media such as P-10 beads available from BioRad.
  • Fig. 6a is a top view of a microfluidic device 200 having a plurality of input ports 202 leading to a plurality of respective processing pathways, one of which is shown as 203.
  • the exemplary processing pathway 203 can be in fluid communication with an exemplary output port 205.
  • the flow arrow shown depicts a direction of fluid movement from input port 202 to output port 205.
  • Input port 202 can be teardrop-shaped having a narrower-end 204 oriented in the same direction as the direction of fluid movement.
  • the processing pathway 203 can be disposed across a length of the microfluidic device, wherein the length of the microfluidic device is greater than a width of the microfluidic device.
  • Fig. 6b is a top view a microfluidic device 210 having a plurality of input ports 212 leading to a plurality of respective processing pathways, one of which is shown as 213.
  • the exemplary processing pathway 213 can be in fluid communication with an exemplary output port 215.
  • a flow arrow depicts a direction of fluid movement from input port 212 to output port 215.
  • the processing pathway 213 can be disposed across a width of the microfluidic device wherein a length of the microfluidic device is greater than the width of the microfluidic device.
  • An alignment pinhole 214 and an alignment notch 216 can be provided in the microfluidic device 210.
  • Fig. 6c is a top view of a sample processing system that includes a rotatable platen 220 having a central axis of rotation 222, and microfluidic devices 224 and 226.
  • Microfluidic device 224 can be oriented on platen 220 such that input ports 225 can be radially closer to axis of rotation 222 than the respective processing pathways 221.
  • microfluidic device 226 can be oriented on platen 220 such that input ports 227 can be radially closer to axis of rotation 222 than the respective processing pathways 228.
  • Microfluidic devices 224, 226 can be held to platen 220 using a holder (not shown). Orientation for placement of microfluidic device 224, 226 can be assisted by one or more alignment pinholes 229, alignment pins (not shown), alignment notches, alignment recesses, or the like, in or included with the holder.
  • a sample processing system having a microfluidic device formed in a substrate and a holder to secure the microfluidic device can include at least one alignment pinhole formed in the substrate and at least one alignment pin in the holder.
  • the at least one alignment pinhole can be complementary to the at least one alignment pin.
  • the alignment pinhole can extend from a first surface of the substrate to an opposing second surface, thus forming a hole through the substrate.
  • the alignment pinhole can partially extend through the first surface, without extending through the substrate to the second surface. Alignment can be by a notch on an edge of the substrate, for example, a semi-circular notch, a triangular notch, or a square notch.
  • at least one alignment pin complementary to the at least one alignment pinhole or notch can be disposed in a holder to hold the microfluidic device to a rotatable platen.
  • a sample processing system having a microfluidic device and a processing apparatus.
  • the microfluidic device includes a substrate having a first surface, an opposite second surface, and a thickness, an input port formed in at least one of the first and second surfaces, and a manifold.
  • the manifold can be formed in the substrate and in fluid communication with the input port.
  • the manifold can include a feed channel that extends in a first direction, and a plurality of branch channels branching off the feed channel.
  • the branch channels can be parallel to one another and can be normal to the feed channel.
  • the processing apparatus can include a rotatable platen having an axis of rotation, a holder capable of holding a microfluidic device on or in the platen and being disposed off-center with respect to the axis of rotation, and a drive unit to rotate the platen about the axis of rotation.
  • the microfluidic device can be held by the holder such that any radius of the platen which is parallel to the length or the width of the microfluidic device does not intercept the other of the width or the length, respectively, of the microfluidic device.
  • the microfluidic device can include a plurality of input ports formed in the substrate, and a respective plurality of manifolds in fluid communication with the plurality of input ports.
  • a method of distributing a liquid sample into a plurality of branch channels in a microfluidic device includes providing a microfluidic device, introducing a liquid sample through an input port and into a feed channel of the microfluidic device, and centrifugally spinning the microfluidic device to force fluid from the feed channel into one or more of a plurality of branch channels of the microfluidic device.
  • the microfluidic device can be part of a sample processing system that includes a rotatable platen with the microfluidic device held therein or thereon.
  • the holder for holding a microfluidic device in or on a platen can be formed using various methods and/or apparatuses.
  • the holder can include a recess in the platen in which a microfluidic device can be placed and recessed.
  • the holder can include pin and hole combinations, pin and notch combinations, clips, swing arms, screws, VELCRO, snaps, straps, tape, adhesive, a door, other fasteners, or a combination thereof to hold the microfluidic device in or on the platen.
  • Fig. 7 a is a top view of a rotatable platen 240 having a central axis of rotation 242 wherein two microfluidic devices 244, 254 can be disposed therein.
  • Each microfluidic device can have an input port 246 that can be, for example, teardrop-shaped.
  • Microfluidic device 244 is disposed in platen 240 such that centerline 252 of platen 240 is parallel to a length or a width of microfluidic devices 244, 254. According to various embodiments, alignment pinhole 260 and alignment notch 262 can be provided in each microfluidic device 244, 254. As shown in Fig. 7a, microfluidic device 254 can be to the left of the centerline 252 of platen 240. Microfluidic device 254 can be left-justified in its orientation. Microfluidic device 244 can be to the right of centerline 252. Microfluidic device 244 can be right- justified in its orientation.
  • the location of microfluidic devices 244 and 254 with respect to the centerline 252 of platen 240 can determine a direction in which teardrop-shaped chamber 246 is canted.
  • narrower-end 250 of teardrop-shaped chamber 246 can point towards the right, as shown in Fig. 7b.
  • the angle of the cant of the teardrop-shaped chambers 246 can be the same for all teardrop-shaped chambers 246 formed in a substrate.
  • narrower-end 250 of teardrop-shaped chambers 246 can be radially oriented.
  • Each teardrop-shaped chamber 246 can have a unique cant, angle.
  • teardrop-shaped chambers 240 can be located along a short side of the substrate.
  • the teardrop-shaped chambers 240 can also be orientated on a long side of the substrate.
  • the teardrop-shaped chambers 240 can be located at any position within the substrate such that the narrower end of the teardrop-shaped chamber is pointed away from the center of a platen to direct fluid toward the narrower portion of the teardrop-shaped chamber 240 and into an adjacent channel, chamber, or well.
  • Fig. 8 is a top view of an exemplary microfluidic device 800 having two input ports 801, 802 for distributing a fluid sample to respective flow distributors 804, 806, each flow distributor being in fluid communication with, or being designed to be valved in communication with a plurality of pathways.
  • the various wells, chambers, channels, vias (not shown), valves, and other features can be manufactured using stereo-lithography, for example.
  • the substrate can be cyclic olefin copolymer, or polycarbonate, for example.
  • Fig. 8 shows an exemplary microfluidic device that includes 384 output ports 808.
  • An exemplary microfluidic device can have a feed channel in fluid communication with 96 parallel branch channels that form 96 pathways.
  • the pathways can each have a PCR chamber 814, a PCR purification chamber 816, a flow restrictor, a vertical flow-splitter that leads to both, a forward sequencing chamber 818 and a reverse sequencing chamber 820, a forward sequencing product purification chamber 822, a reverse sequencing product purification chamber 824, a purified forward sequencing product 826 output chamber, a purified reverse sequencing product output chamber 828, a plurality of opening and closing valves, or a combination thereof
  • Channels, wells, and chambers can be formed in a first and/or a second surface of the microfluidic device substrate 812. Vias and columns can be used to facilitate fluid communication between features formed respectively in the two surfaces of the device.
  • Exemplary spacing for various features in a microfluidic device can be as described herein, although other suitable spacing as known to those of ordinary skill in the art, can also be used.
  • An exemplary microfluidic device can have a width of from about 80 to about 90 mm
  • the microfluidic device can have a length of from about 115 mm to about 130 mm.
  • Two or more output wells in the microfluidic device can be disposed in the substrate such that a center of a first output well is about 2.25 mm from a center of a second output well along a first axis.
  • Two or more output wells in the microfluidic device can be disposed in the substrate such that a center of the first output well is about 0.6 mm, for example, about 0.5625 mm, from a center of the second output well along a second axis.
  • the substrate for the microfluidic device can have a thickness of about 2 mm
  • One or more output wells and/or processing chambers in the microfluidic device can have a depth of about 1.5 mm
  • One or more output wells in the microfluidic device can have a diameter of about 1.5 mm
  • One or more processing chambers in the microfluidic device can have a depth of about 0.9 mm
  • One or more processing chamber in the microfluidic device can have a width of about 0.6 m
  • One or more processing chamber in the microfluidic device can have a length of about 0.5 mm, about 1.0 mm, about 2.5 mm, or about 3.5 mm Channels connecting two or more processing chambers and/or an output wells can be rectangular-shaped.
  • the channels can have depths of about 0.25 mm
  • the channels can have widths of about 0.25 mm
  • the channels can have lengths of from about 4 mm to about 25 mm
  • the channels can be disposed in the substrate about 0.6 mm, for example, about 0.5625 mm, from a center of a second channel.
  • the channels can be straight.
  • the channels can have one or more turns of any suitable angle or curvature, for example, of about 150 degrees.
  • Microfluidic devices and systems as described herein facilitate the flow of fluids through the microfluidic device when subjected to a centripetal force. Flow splitters and flow distributors capable of dividing fluid samples or reagents into aliquots are described. The features and methods described herein can be used with any microfluidic device that utilizes centrifugation for fluid transport.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Micromachines (AREA)

Abstract

L'invention concerne des dispositifs, des ensembles et des systèmes micro-fluidiques, ainsi que des procédés de manipulation de micro-échantillons de fluides. L'invention concerne également des dispositifs micro-fluidiques possédant une pluralité de caractéristiques de traitement spécialisées facilitant un transfert de fluide centripète.
PCT/US2003/022226 2002-07-26 2003-07-16 Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete WO2004011365A2 (fr)

Priority Applications (4)

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JP2005505600A JP2005533651A (ja) 2002-07-26 2003-07-16 求心力による流体の移動を助長するミクロチャンネル設計特徴
EP03771636A EP1534429A4 (fr) 2002-07-26 2003-07-16 Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete
AU2003253944A AU2003253944A1 (en) 2002-07-26 2003-07-16 Micro-channel design features that facilitate centripetal fluid transfer
CA002493700A CA2493700A1 (fr) 2002-07-26 2003-07-16 Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete

Applications Claiming Priority (10)

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US39885102P 2002-07-26 2002-07-26
US60/398,851 2002-07-26
US39954802P 2002-07-30 2002-07-30
US60/399,548 2002-07-30
US36633003A 2003-01-03 2003-01-03
US10/336,706 2003-01-03
US10/336,274 US7198759B2 (en) 2002-07-26 2003-01-03 Microfluidic devices, methods, and systems
US10/336,706 US7214348B2 (en) 2002-07-26 2003-01-03 Microfluidic size-exclusion devices, systems, and methods
US10/336,274 2003-01-03
US10/366,330 2003-01-03

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US7323660B2 (en) 2005-07-05 2008-01-29 3M Innovative Properties Company Modular sample processing apparatus kits and modules
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US7569186B2 (en) 2001-12-28 2009-08-04 3M Innovative Properties Company Systems for using sample processing devices
US7754474B2 (en) 2005-07-05 2010-07-13 3M Innovative Properties Company Sample processing device compression systems and methods
US7763210B2 (en) 2005-07-05 2010-07-27 3M Innovative Properties Company Compliant microfluidic sample processing disks
WO2010118637A1 (fr) * 2009-04-14 2010-10-21 Huang Yanyi Dispositif de distribution microfluidique, procédé de production, et application correspondants
US7939018B2 (en) 2000-06-28 2011-05-10 3M Innovative Properties Company Multi-format sample processing devices and systems
US9067205B2 (en) 2011-05-18 2015-06-30 3M Innovative Properties Company Systems and methods for valving on a sample processing device
US9725762B2 (en) 2011-05-18 2017-08-08 Diasorin S.P.A. Systems and methods for detecting the presence of a selected volume of material in a sample processing device
WO2024221602A1 (fr) * 2023-04-26 2024-10-31 深圳华大智造科技股份有限公司 Verre à lame, séquenceur et appareil d'analyse biochimique

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US7939018B2 (en) 2000-06-28 2011-05-10 3M Innovative Properties Company Multi-format sample processing devices and systems
US6814935B2 (en) 2000-06-28 2004-11-09 3M Innovative Properties Company Sample processing devices and carriers
US7435933B2 (en) 2000-06-28 2008-10-14 3M Innovative Properties Company Enhanced sample processing devices, systems and methods
US7445752B2 (en) 2000-06-28 2008-11-04 3M Innovative Properties Company Sample processing devices and carriers
US7569186B2 (en) 2001-12-28 2009-08-04 3M Innovative Properties Company Systems for using sample processing devices
USD564667S1 (en) 2005-07-05 2008-03-18 3M Innovative Properties Company Rotatable sample processing disk
US7754474B2 (en) 2005-07-05 2010-07-13 3M Innovative Properties Company Sample processing device compression systems and methods
US7763210B2 (en) 2005-07-05 2010-07-27 3M Innovative Properties Company Compliant microfluidic sample processing disks
US7767937B2 (en) 2005-07-05 2010-08-03 3M Innovative Properties Company Modular sample processing kits and modules
US7323660B2 (en) 2005-07-05 2008-01-29 3M Innovative Properties Company Modular sample processing apparatus kits and modules
US8080409B2 (en) 2005-07-05 2011-12-20 3M Innovative Properties Company Sample processing device compression systems and methods
WO2010118637A1 (fr) * 2009-04-14 2010-10-21 Huang Yanyi Dispositif de distribution microfluidique, procédé de production, et application correspondants
US9067205B2 (en) 2011-05-18 2015-06-30 3M Innovative Properties Company Systems and methods for valving on a sample processing device
US9725762B2 (en) 2011-05-18 2017-08-08 Diasorin S.P.A. Systems and methods for detecting the presence of a selected volume of material in a sample processing device
WO2024221602A1 (fr) * 2023-04-26 2024-10-31 深圳华大智造科技股份有限公司 Verre à lame, séquenceur et appareil d'analyse biochimique

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WO2004011365A3 (fr) 2004-06-10
JP2005533651A (ja) 2005-11-10
AU2003253944A1 (en) 2004-02-16
EP1534429A4 (fr) 2005-09-07
CA2493700A1 (fr) 2004-02-05

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