EP2847465B1 - Mikrofluidische pumpe - Google Patents

Mikrofluidische pumpe Download PDF

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Publication number
EP2847465B1
EP2847465B1 EP13767323.2A EP13767323A EP2847465B1 EP 2847465 B1 EP2847465 B1 EP 2847465B1 EP 13767323 A EP13767323 A EP 13767323A EP 2847465 B1 EP2847465 B1 EP 2847465B1
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EP
European Patent Office
Prior art keywords
less
pump
microns
microchannel
groove
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Active
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EP13767323.2A
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English (en)
French (fr)
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EP2847465A4 (de
EP2847465A1 (de
Inventor
Remus Haupt
Horst BÖßNECK
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Alere San Diego Inc
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Alere San Diego Inc
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Publication of EP2847465A4 publication Critical patent/EP2847465A4/de
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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F04B43/14—Machines, pumps, or pumping installations having flexible working members having peristaltic action having plate-like flexible members
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F04B43/1238—Machines, pumps, or pumping installations having flexible working members having peristaltic action using only one roller as the squeezing element, the roller moving on an arc of a circle during squeezing
    • F04B43/1246—Machines, pumps, or pumping installations having flexible working members having peristaltic action using only one roller as the squeezing element, the roller moving on an arc of a circle during squeezing the roller being placed at the outside of the tubular flexible member
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F04B43/1253—Machines, pumps, or pumping installations having flexible working members having peristaltic action by using two or more rollers as squeezing elements, the rollers moving on an arc of a circle during squeezing
    • F04B43/1261—Machines, pumps, or pumping installations having flexible working members having peristaltic action by using two or more rollers as squeezing elements, the rollers moving on an arc of a circle during squeezing the rollers being placed at the outside of the tubular flexible member
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/12—Machines, pumps, or pumping installations having flexible working members having peristaltic action
    • F04B43/1253—Machines, pumps, or pumping installations having flexible working members having peristaltic action by using two or more rollers as squeezing elements, the rollers moving on an arc of a circle during squeezing
    • F04B43/1292—Pumps specially adapted for several tubular flexible members

Definitions

  • the invention relates to microfluidics technology, and more particularly to a microfluidic pump for control of fluid flow through microchannels.
  • Microfluidics systems are of significant value for acquiring and analyzing chemical and biological information using very small volumes of liquid. Use of microfluidic systems can increase the response time of reactions, minimize sample volume, and lower reagent and consumables consumption. When volatile or hazardous materials are used or generated, performing reactions in microfluidic volumes also enhances safety and reduces disposal quantities.
  • Microfluidic devices have becoming increasingly important in a wide variety of fields from medical diagnostics and analytical chemistry to genomic and proteomic analysis. They may also be useful in therapeutic contexts, such as low flow rate drug delivery.
  • micropump may be used to mix reagents and transport fluids between a disposable analysis platform component of the system and an analysis instrument (e.g. , an analyte reader with display functions). Yet controlling the direction and rate of fluid flow within the confines of a microfluidic device, or achieving complex fluid flow patterns inside microfluidic channels is difficult.
  • a microfluidic pump has been developed in order to provide low cost, high accuracy means for onboard sample handling in disposable assay devices.
  • Devices utilizing the microfluidic pump, as well as methods for manufacture and performing a microfluidic process are also provided.
  • the invention provides a microfluidic pump, comprising: a microchannel defined by (a) a groove in a first surface of a first substrate, and (b) a second surface of a second substrate; and an actuator configured to compress a portion of the second substrate into the groove of the first substrate without substantially deforming the groove, characterized in that the actuator is configured to translate along an axis of the groove.
  • the groove has a height and the height is at least about 10 microns, at least about 20 microns, at least about 30 microns, or at least about 50 microns and/or wherein the groove has a height and the height is about 1000 microns or less, about 500 microns or less, about 250 microns or less, about 125 microns or less, about 100 microns or less, about 75 microns or less.
  • the first and second substrates are substantially planar.
  • the channel has an inlet and an outlet and a distance between the inlet and the outlet is at least about 1 mm, at least about 2.5 mm, at least about 5 mm, at least about 10 mm, at least about 25 mm and/or wherein the channel has an inlet and an outlet and a distance between the inlet and the outlet is about 250 mm or less, 100 mm or less, about 75 mm or less, about 50 mm or less, about 25 mm or less.
  • the pump is disposed in fluidic communication with a microfluidic device.
  • the pump comprises at least one microchannel configured to receive a liquid sample suspected of containing at least one target and the microchannel comprises at least one reagent for use in determining the presence of the at least one target.
  • the pump is configured to produce a gas pressure acting upon a distal gas-liquid interface of the liquid sample when the distal gas-liquid interface of the liquid sample is disposed within the microchannel of the microfluidic device.
  • a proximal gas-liquid interface of the liquid sample may be exposed to an ambient atmosphere.
  • the gas pressure acting upon the distal gas-liquid interface of the liquid sample may be less than an ambient gas pressure.
  • the first and second substrates may be disposed within the microfluidic device.
  • the microchannel of the microfluidic device comprises the liquid sample disposed therein, optionally wherein the liquid sample comprises urine or at least one liquid component of blood.
  • the actuator is configured to provide a rate of flow of the liquid sample within the microchannel of the microfluidic device of at least about 1 nl/s, at least about 5 nl/s, at least about 10 nl/s, at least about 25 nl/s, at least about 50 nl/s, at least about 100 nl/s, at least about 250 nl/s, at least about 500 nl/s at least about 1000 nl/s and/or wherein the actuator is configured to provide a rate of flow of the liquid sample within the microchannel of the microfluidic device of about 10,000 nl/s or less, about 5,000 nl/s or less, about 2,500 nl/s or less, at least about 1000 nl/s or less.
  • the channel has an uncompressed area and, when compressed by the actuator, the compressed portion of the second substrate occludes at least about 50%, at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially all of the uncompressed area of the channel.
  • the groove in the uncompressed state, has a width and the width is at least about 50 microns, at least about 100 microns, at least about 200 microns, at least about 500 microns, optionally wherein, in the compressed state, the width of the groove is at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially the same as in the uncompressed state.
  • the groove in the compressed state, has a width and the width is about 2000 microns or less, about 1500 microns or less, about 1000 microns or less, about 750 microns or less about 600 microns or less, optionally wherein, in the compressed state, the height of the groove is at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially the same as in the uncompressed state.
  • the second substrate in the uncompressed state, has a first thickness overlying the groove and a second thickness spaced apart laterally a first distance from the groove and wherein the second thickness is at least about 110%, at least about 125%, at least about 150%, at least about 175%, or at least about 200% greater than the first thickness, optionally wherein the first distance is at about 50% greater than a width of the groove, about 75% greater than a width of the groove, about 100% greater than a width of the groove, about 200% greater than a width of the groove.
  • the microfluidic pump module may include a first plate element and a second plate element, the first plate element being elastomeric and the second plate element being non-elastomeric.
  • the second plate element includes a microchannel formed on a surface of the second plate element, and the first and second plate elements are coupled to form a fluid tight seal along the boundary of the microchannel defining a fluid flow path.
  • the microfluidic device includes (a) a rigid substrate having a microchannel formed on a surface thereof; and (b) a flexible layer coupled to and overlying the rigid substrate thereby enclosing the microchannel, wherein the flexible layer comprises a raised element disposed over a portion or all of the microchannel.
  • the device further includes a fluid tight seal formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary.
  • the microfluidic device includes (a) a rigid substrate having a microchannel formed on a surface thereof; and (b) a flexible layer coupled to and overlying the rigid substrate thereby enclosing the microchannel, wherein the flexible layer has a flat surface disposed over a portion or all of the microchannel.
  • the device further includes a fluid tight seal formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary.
  • microfluidic device utilizing the microfluidic pump module described herein, wherein the pump module comprises at least two independent microchannels arranged in a substantially parallel manner.
  • One or more actuators are provided which act upon the two or more microchannels simultaneously, thereby providing means to pump two fluids separate from one another.
  • the microchannels may have identical cross sectional areas, such that the volume of fluid transported per unit distance of the microchannel is substantially the same.
  • the at least two microchannels may have different cross sectional areas, in which instance the volume of fluid transported per unit distance of the microchannel is different.
  • the outermost channel has a radius r2, which is three times the radius of the inner most channel r1
  • three times the volume of fluid will be transported in the outermost channel compared with the innermost channel per revolution of the actuator.
  • the method includes (a) applying a voltage to a microfluidic pump module as described herein.
  • the applied voltage activates a motor which advances an actuator element, such as one or more rollers, which is rotatably engaged with the second substrate, causing deformation of the second substrate into the microchannel formed on the surface of the first substrate.
  • Deformation of the elastomeric second substrate into the microchannel forces fluid within the microchannel along the microchannel resulting in a fluid flow.
  • the first substrate is formed from a material having a Shore D hardness of between about 75 and about 90. Such materials include, but are not limited to, polystyrene, polypropylene, polymethylmethacrylate, polycarbonate and the like.
  • the microchannel or groove formed in the surface of the first substrate is dimensionally stable, by which is meant that when the second substrate is deformed into the groove in the first substrate, the width of the groove is at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially the same as in the uncompressed state and height the groove is at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially the same as in the uncompressed state.
  • the dimensions of the groove are thus considered to be essentially unchanged as a consequence of the deformation of the second substrate into the first substrate,
  • the second substrate is formed from a material having a Shore A hardness of between about 15 and 90.
  • Such materials include, but are not thermoplastic elastomer (TPE), polydimethylsiloxane (PDMS), silicone rubber, fluoroelastomer and the like.
  • TPE thermoplastic elastomer
  • PDMS polydimethylsiloxane
  • silicone rubber fluoroelastomer and the like.
  • Such materials are considered to be dimensionally unstable, by which is meant that when a compressive force or a stretching force is applied to such polymeric materials the material deforms, either through elongation in one or more directions, or the material compresses in one or more dimensions.
  • the method includes coupling a rigid substrate having a microchannel formed on a surface thereof, to a flexible layer overlying the rigid substrate and enclosing the microchannel.
  • a fluid tight seal is formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary.
  • the rigid substrate and the flexible layer are coupled via a laser welding process.
  • the process includes:
  • the method includes coupling a rigid substrate having a microchannel formed on a surface thereof, to a flexible layer overlying the rigid substrate and enclosing the microchannel.
  • a fluid tight seal is formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary.
  • the rigid substrate and the flexible layer are coupled via a process of over-molding. The process includes:
  • a microfluidic pump and device containing the pump have been developed in order to provide, in embodiments, low cost, high accuracy and low flow rate means for onboard sample handling for disposable assay devices.
  • the rate of fluid flow within the pump is essentially constant even at very low flow rates.
  • the pump comprises a first substrate and a second substrate secured with respect to one another to provide a structure having one or more microchannels which are sealed along the boundaries of the microchannels thereby defining fluid flow paths.
  • microchannel structures (40), e.g., grooves, are formed in a major surface of a first substrate (20) formed, e.g., of a non-elastomeric or rigid material.
  • a deformable second substrate (10) formed, e.g., of an elastomer, is secured with respect to first substrate 20 to create enclosed microchannels (40) having a fluid tight seal along their boundaries.
  • the second substrate In the compressed state, the second substrate typically occludes a sufficient portion of the microchannel (40) to displace a substantial portion of fluid from microchannel (40) at the site of compression.
  • the second substrate may occlude a sufficient portion of the microchannel (40) to separate fluid disposed within microchannel (40) on one side of the site of compression from fluid disposed within microchannel (40) on the other side of the site of compression.
  • the second substrate occludes, in the compressed state, at least about 50%, at least about 75%, at least about 90%, at least about 95%, at least about 97.5%, at least about 99%, or essentially all of the uncompressed cross-sectional area of the groove at the site of compression.
  • the compression may create a fluid-tight seal between the first and second substrates within the groove at the site of compression.
  • fluid e.g., a liquid
  • the fluid-tight seal may be transient, e . g ., the second substrate may fully or partially relax upon removal of the compression thereby fully or partially reopening the groove.
  • the groove has a first cross-sectional area in an uncompressed state and a second cross-sectional area in the compressed state.
  • the portion of the elastomer is compressed into the groove without substantially deforming the groove.
  • a ratio of the cross-sectional area at the site of compression in the compressed state to the cross-sectional area at the same site in the uncompressed state may be at least about 0.75, at least about 0.85, at least about 0.925, at least about 0.975, or about 1.
  • the height of the groove e.g.
  • the maximum height of the groove at the site of compression, in the compressed state may be at least about 75%, at least about 85%, at least about 90%, at least about 95%, or about 100% of the height of the groove at the same site in the uncompressed state.
  • the width of the groove, e.g. , the maximum width of the groove at the site of compression, in the compressed state may be at least about 75%, at least about 85%, at least about 90%, at least about 95%, or about 100% of the width of the groove at the same site in the uncompressed state.
  • a raised element (30), such as a bump, is present on the elastomer (10), which may be placed over the microchannel region (40), thereby increasing the thickness of elastomeric material which may aid sealing of the elastomer into the channel when compressed against the non-elastic component (20).
  • the elastomer in the uncompressed state, may have a first thickness overlying the groove and a second thickness spaced apart laterally a first distance from the center of the groove.
  • the second thickness is at least about 110%, at least about 125%, at least about 150%, at least about 175%, or at least about 200% greater than the first thickness.
  • the second thickness may be at least about 500% or less, about 400% or less, about 300% or less, or at about 250% or less greater than the first thickness.
  • the first distance may be at least about 1 mm, at least about 2.5 mm, at least about 5 mm, or at least about 1 cm.
  • the first distance may be about 2.5 cm or less, about 2 cm or less, about 1.5 cm or less, or about 1.25 cm or less. In embodiments, the first distance is at about 1.5 times greater, about 1.75 times greater, about 2 times greater, or about 4 times greater than a width, e.g. , a maximum width, of the groove.
  • the first distance may be about 25 times greater or less, about 20 times greater or less, about 15 times greater or less, or about 10 times greater or less than a width, e.g. , a maximum width, of the groove.
  • the microfluidic pump module (100) includes a first elastomeric plate element (10) and a second rigid plate element (20).
  • the second plate element (20) includes a microchannel (40) formed on a surface of the second plate element (20), and the first and second plate elements are coupled to form a fluid tight seal along the boundary of the microchannel (40) defining a fluid flow path.
  • the microfluidic device (100) includes a rigid substrate (20) having a microchannel (40) formed on a surface thereof and a flexible layer (10) coupled to and overlying the rigid substrate (20) thereby enclosing the microchannel (40).
  • microfluidic device which again with reference to Figures 1A and 1B , the reverse orientation is provided.
  • microchannel (40) is formed in flexible layer (10); and rigid substrate (20) is provided with a flat surface profile, such that when flexible layer (10) is coupled to and overlying rigid substrate (20) a microchannel (40) is formed therebetween.
  • the flexible layer (10) comprises a raised element (30) disposed over a portion or all of the microchannel (40).
  • the raised element (30) provides an increased cross-section thickness in the area which coincides with the microchannel (40). This assists in creating a water tight seal between the deformed elastomeric material (60) advanced into the microchannel (40) with the surface of the microchannel.
  • the raised element (30) may be one of a number of suitable shapes such as a bump.
  • the flexible layer (10) has no raised element (30), in which case microchannel (40) is covered entirely by flexible layer (10) which has a flat upper surface profile, which surface is not in contact with rigid substrate (20).
  • microchannels (40) may be formed on a surface of the rigid substrate (20) by any number of suitable techniques known in the art.
  • microchannels may be formed by deposition of materials through a mask, chemical etching, laser etching, molding of a plastic substrate, and the like.
  • a fluid tight seal is also formed between the rigid substrate (20) and the flexible layer (10) along a periphery of the microchannel (40) forming an enclosed capillary having a defined fluid flow path.
  • Microchannels may be dimensioned to define the volume within the microchannel and resultant flow rate for a given rate at which the elastomer is progressively deformed into the microchannel.
  • the high quality and precision of the so formed microchannel results in a microfluidic pump element that can achieve very slow and consistent flow rates, which may not otherwise be achieved if alternate processes of manufacture were employed.
  • a microchannel may be dimensioned such that it has a constant width dimension and a constant depth dimension along all or a portion of its length.
  • a microchannel will have a constant width dimension and a constant depth dimension along a length of the microchannel which engages a deformation element.
  • a microchannel has a width dimension of between 500 to 900 microns and a depth dimension of between 40 to 100 microns.
  • the device may be adapted for a flow rate within the microchannel of between 0.001 ⁇ l/s to 5.0 ⁇ l/s.
  • FIGS 1A and 1B depict a microchannel (40) in which the bottom surface of the microchannel is arced and defines a concave circular geometry.
  • the microchannel (40) may have a rounded, elliptical or generally U shaped bottom.
  • the microchannel has an arced shaped bottom having a radius of curvature of between 0.7 and 0.9 mm.
  • Figure 2 is a cross-sectional view of a portion of a microfluidic device in one embodiment of the invention in which specific dimensions (shown in mm) are described for various features.
  • microchannels (40) may be modified, for example by varying hydrophobicity.
  • hydrophobicity may be modified by application of hydrophilic materials such as surface active agents, application of hydrophobic materials, construction from materials having the desired hydrophobicity, ionizing surfaces with energetic beams, and/or the like.
  • a device of the present invention may include a plurality of microchannels (40), each having various geometries and disposed on the rigid substrate (20) (or in the alternate on the flexible layer (10)) in a variety of patterns.
  • microchannels (40) may be linear or extend arcuately along the surface of the rigid substrate (20).
  • Figures 3 and 4 illustrate microchannels (40) being disposed as generally circular or spiral geometries.
  • Figure 3 is a perspective view of a device in which microchannels (40) are disposed as spirals, a smaller volume microchannel disposed within a microchannel having a larger volume.
  • Figure 4 is a top view of a device in which the microchannel (40) is disposed in a spiral manner having ports (100) and (110) which may be in fluid communication with one or more additional microchannels or structures.
  • the circular or spiral portion of the microchannel has a length of between 20 to 100 mm.
  • a spiral or generally circular shaped microchannel allows for fluid to be advanced through the microchannel of the pump module or device by a deformation element (50) that is radially coupled to the device.
  • Figure 5 is an illustration depicting a pump module and device of the present invention in which multiple deformation elements (50) are radially coupled and configured to engage a microchannel having a circular or spiral geometry.
  • the deformation elements (50) are provided in a housing (80) configured to radially traverse one or more microchannels provided on the microfluidic laminate structure (110) when the structure is placed in contact with the deformation elements (50) (spiral microchannel is disposed on the opposite side of laminate structure (110) shown).
  • the rotational direction of the deformation elements (50) with relation to the micro fluidic laminate structure (110) dictates the direction of flow within the microchannel.
  • fluid flow through the pump may be bidirectional.
  • Housing (80) may be rotated by applying a voltage to a motor controlling movement thereof.
  • a method for performing a microfluidic process which includes applying a voltage to a device as described herein.
  • the applied voltage activates a motor which advances at least one deformation element (50), such as one or more rollers, which are rotatably engaged with the elastomeric first plate element (10), causing deformation of a raised element (30) on the flexible layer (10) into the microchannel (40) formed on the surface of the rigid substrate (20).
  • a wide range of pulses per second may be applied to the electrical motor thereby effectuating a wide range of flow rates within microchannels.
  • the fluid flow is essentially constant, with little or no shear force being imposed on the fluid, even at very low flow rates. These characteristics of the pump enhance the accuracy of analyses performed with it (e.g ., analyte integrity is preserved by minimizing exposure of sample components to shear and degradation), while low flow rates provide sufficient time for chemical reactions to occur.
  • a low, constant pumped flow rate can also be very useful in drug delivery, to ensure dosing accuracy.
  • between 100 and 10,000 pulses per second may be applied resulting in a flow rate of between 0.001 ⁇ l/s to 5.0 ⁇ l/s through microchannels.
  • the design of the present invention allows forces within microchannels of the present invention to remain fairly constant over a wide range of applied pulses.
  • Figures 7-9 are graphs plotting forces generated within microchannels as a function of the number of pulses per second. As depicted in the graphs of Figures 7-9 , forces generated within the microchannels are relatively constant over a wide range of pulses per second indicating substantially constant flow with minimal shear.
  • FIGS 6A-6C illustrate various configurations in different embodiments of the invention in which at least one spiral or circular microchannel is provided.
  • Circular or spiral microchannels (40) may be disposed such that they are in fluid communication with one or more additional microchannels (140) through ports (100) and (110).
  • Additional microchannels (140) may be provided with various reagents, immobilized therein or otherwise provided such that a biological assay may be performed on a fluid sample.
  • a fluid tight seal is formed between the rigid substrate (20) and the flexible layer (10) along a periphery of the microchannel (40) forming an enclosed capillary having a defined fluid flow path.
  • Figure 10 illustrates a portion of a device having a generally spiral microchannel in which a fluid tight seal (140) is shown along the periphery of the microchannel (40).
  • a variety of methods may be utilized to couple rigid substrate (20) to the elastomer that forms flexible layer (10).
  • the parts may be joined together using UV curable adhesive or other adhesive that permits for movement of the two parts relative one another prior to curing of the adhesive/creation of bond.
  • Suitable adhesives include a UV curable adhesive, a heat cured adhesive, a pressure sensitive adhesive, an oxygen sensitive adhesive, and a double-sided tape adhesive.
  • the parts may be coupled utilizing a welding process.
  • a welding process including an ultrasonic welding process, a thermal welding process, and a torsional welding process.
  • the parts may be joined using a process of two-shot molding or overmolding, in which case first one polymer and then the other is injected into a mold tool.
  • a process of two-shot molding or overmolding in which case first one polymer and then the other is injected into a mold tool.
  • elastomeric and non-elastomeric polymers can be joined in this way to achieve fluid tight seals between the parts.
  • a process of laser welding may be utilized.
  • the process includes:
  • the benefits of such approaches mean that (i) the parts may be manipulated (slid against one another) during manufacture to achieve desired alignments, (ii) intricate forms can be achieved in the non-elastomer - linear or arcuate channels (or combinations thereof) with a plurality of channel geometries, (iii) connections with the device may be made via the non-elastomeric material, which is dimensionally stable.
  • additional microchannels and structures may be provided to allow the device to perform a number of different types of biological assays or reactions.
  • additional fluid or reagent reservoirs may be provided, one or more of which act as a reaction chamber for example. Additional structure and depicted in the following example which is intended to illustrate but not limit the invention.
  • planar circular or spiral peristaltic pump of the present invention for use in low cost diagnostic products consisting of an instrument and consumable, where the consumable requires sealing due to a potential high risk of contamination.
  • the method to perform pumping sample fluids to deposited chemicals followed by mixing of sample fluid with deposited chemicals in a low cost manner involves using only one actuator, for example a DC or stepper motor (1) incorporated into the instrument.
  • the peristaltic pump consists of a planar circular or spiral annular microchannel (2) as a feature of a substrate (3) of the consumable (4) and the deforming membrane of the pump is provided by an elastomeric layer (5) which is deformed by the pump rollers (6).
  • Concentric to the annular pump channels is the mixing chamber (7) which contains a magnetic or magnetized puck (8).
  • Concentric to the pump rollers of the instrument is a structure comprising a mixing head (9) which is magnetic or magnetized and is magnetically coupled to the puck.
  • the pump and mixing chamber are fluidically connected, thus fluid can be pumped from the pump microchannels into the mixing chamber as the motor rotates in a predetermined direction.
  • the instrument component of the pump comprises a suitable mechanism to provide pumping and mixing functionality when the motor is rotated in a certain direction, but only mixing functionality when the motor is rotated in the opposite direction, for example a ratchet system implemented by a pawl (10) and a compression spring (11) whereby the mixing head rotates with the pump rollers in one rotational direction of the motor and whereby the pump rollers disengage from the motor when the motor rotates in the other direction, thus providing rotation of the mixing head only.
  • the compression spring may also provide the necessary contact force on the pump channels to facilitate effective pumping.
  • Table 1 A sequence of events is provided in Table 1 below. Table 1. Motor Operation Effect on fluid Motor rotates clockwise Pump rotor is engaged and sample fluid is transported from one location on the consumable into the mixing chamber. Magnetic force to the puck is also provided. Motor stops Transportation of sample fluid is stopped. Motor rotates counter clockwise Pump rotor is disengaged and sample fluid remains in mixing chamber. Only the puck moves due to magnetic force and sample is mixed with deposited chemicals. Motor rotates clockwise Pump rotor is engaged and chemicals mixed with sample fluid are transported from the mixing chamber to another location on the consumable.
  • FIG. 12 Another embodiment provides an annular mixing chamber internal or external to the pump channels. This embodiment could feasibly be produced at a lower cost than the first embodiment and is described with reference to Figure 12 .
  • the spiral or circular pump channel (1) as a feature in a substrate (2) is overlaid with an elastomeric membrane (3) and deformed by pump rollers (4) in a similar manner to that described in Figure 11 .
  • the mixing chamber is an annular channel (4) as a concentric feature to the pump channel but located on the reverse face of the pump channel substrate.
  • bearing balls (5) which are magnetically coupled to a magnetic or magnetized element on the rotor (6) such that as the rotor rotates the bearing balls also rotate in the annular channel, thus providing mixing of chemicals initially deposited inside the annular channel.
  • the drive mechanism to achieve mixing and pumping in one rotational direction of the motor and just mixing in the other rotational direction of the motor is envisaged to be similar to that described with reference to Figure 11 .
  • Two concentric circular or spiral pump channels are included in the consumable each having their own fluid path, for example, the inner microchannel (1) provides fluidic pumping of the sample fluid (2) and the outer microchannel (3) provides fluidic pumping for a dilution fluid (4).
  • Each microchannel shares the same pump rollers (5), such that rotation of the drive shaft by the low cost motor causes both sample fluid and buffer fluid to be pumped.
  • this peristaltic pump can be designed to accommodate multiple fluidic channels on different radii if desired.
  • the sample that is transported is first required to be mixed with stored deposited chemicals (6) located within the mixing chamber (7), followed by a dilution step using a dilution fluid.
  • the motor rotates in a certain direction the pump rollers engage with the pumping membrane to transport both sample fluid and dilution fluid into the consumable, as the mixing chamber fills with sample fluid, the dilution fluid fills a secondary chamber (8) which is sized according to the amount of dilution fluid required and the geometry of the dilution fluid pumping channels and the mixing chamber volume.
  • the motor stops both dilution fluid and sample fluid remain in their respective chambers.
  • an equivalent mechanism as described above could be implemented which rotates the motor in the opposite direction to only provide mixing.
  • the motor rotates to engage the pump rollers which transport the sample and dilution fluid to a location inside the consumable which combines the two fluids (9).
  • passive mixing features (10) may be included at the fluid combining region.
  • the motor continues to rotate to pump the two fluids, the diluted sample can be transported to another location on the consumable, for example a location to carry out detection of an analyte (11).
  • the pump design allows the pump to be sealed to the environment.
  • a wide range of pulses per second may be applied to the electrical motor thereby effectuating a wide range of flow rates within microchannels, including very low flow rates.
  • the fluid flow is essentially constant, with little or no shear force being imposed on the fluid, even at very low flow rates.
  • These characteristics of the pump enhance the accuracy of analyses performed with it (e.g ., analyte integrity is preserved by minimizing exposure of sample components to shear and degradation), while low flow rates provide sufficient time for chemical reactions to occur.
  • a low, constant pumped flow rate can also be very useful in drug delivery, to ensure dosing accuracy.

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Claims (17)

  1. Mikrofluidische Pumpe, die Folgendes umfasst:
    einen Mikrokanal (40), definiert durch (a) eine Nut (1, 40) in einer ersten Oberfläche eines ersten Substrats (20), und (b) eine zweite Oberfläche eines zweiten Substrats (10); und
    einen Aktuator (50), ausgelegt zum Eindrücken eines Teils des zweiten Substrats (10) in die Nut des ersten Substrats (20), ohne die Nut (1, 40) wesentlich zu verformen, dadurch gekennzeichnet, dass
    der Aktuator (50) dazu ausgelegt ist, sich entlang einer Achse der Nut (1, 40) zu verschieben.
  2. Pumpe nach Anspruch 1, wobei die Nut (1, 40) eine Höhe hat und die Höhe mindestens etwa 10 Mikrometer, mindestens etwa 20 Mikrometer, mindestens etwa 30 Mikrometer oder mindestens etwa 50 Mikrometer ist und/oder wobei die Nut (1, 40) eine Höhe hat und die Höhe etwa 1000 Mikrometer oder weniger, etwa 500 Mikrometer oder weniger, etwa 250 Mikrometer oder weniger, etwa 125 Mikrometer oder weniger, etwa 100 Mikrometer oder weniger, etwa 75 Mikrometer oder weniger ist.
  3. Die Pumpe nach einem der vorhergehenden Ansprüche, wobei das erste und das zweite Substrat (20, 10) im Wesentlichen eben sind.
  4. Pumpe nach einem der vorhergehenden Ansprüche, wobei der Kanal einen Einlass und einen Auslass aufweist und ein Abstand zwischen dem Einlass und dem Auslass mindestens etwa 1 mm, mindestens etwa 2,5 mm, mindestens etwa 5 mm, mindestens etwa 10 mm, mindestens etwa 25 mm ist und/oder wobei der Kanal einen Einlass und einen Auslass aufweist und ein Abstand zwischen dem Einlass und dem Auslass etwa 250 mm oder weniger, 100 mm oder weniger, etwa 75 mm oder weniger, etwa 50 mm oder weniger, etwa 25 mm oder weniger ist.
  5. Pumpe nach einem der vorhergehenden Ansprüche, wobei die Pumpe in Fluidverbindung mit einer mikrofluidischen Vorrichtung angeordnet ist.
  6. Pumpe nach Anspruch 5, wobei die Pumpe mindestens einen Mikrokanal (1, 40) umfasst, der dazu ausgelegt ist, eine Flüssigkeitsprobe aufzunehmen, von der vermutet wird, dass sie zumindest ein Ziel enthält, und wobei der Mikrokanal (1, 40) zumindest ein Reagens zur Verwendung beim Bestimmen der Anwesenheit des zumindest einen Ziels umfasst.
  7. Pumpe nach Anspruch 6, wobei die Pumpe dazu ausgelegt ist, einen Gasdruck zu erzeugen, der auf eine distale Gas-Flüssigkeit-Schnittstelle der Flüssigkeitsprobe wirkt, wenn die distale Gas-Flüssigkeit-Schnittstelle der Flüssigkeitsprobe innerhalb des Mikrokanals (1, 40) der mikrofluidischen Vorrichtung angeordnet ist.
  8. Pumpe nach Anspruch 7, wobei eine proximale Gas-Flüssigkeit-Schnittstelle der Flüssigkeitsprobe einer umgebenden Atmosphäre ausgesetzt ist.
  9. Pumpe nach Anspruch 7 oder Anspruch 8, wobei der Gasdruck, der auf die distale Gas-Flüssigkeit-Schnittstelle der Flüssigkeitsprobe wirkt, kleiner als ein umgebender Gasdruck ist.
  10. Pumpe nach einem der Ansprüche 5-9, wobei das erste und das zweite Substrat (20, 10) innerhalb der mikrofluidischen Vorrichtung angeordnet sind.
  11. Pumpe nach einem der Ansprüche 5-10, wobei der Mikrokanal (1, 40) der mikrofluidischen Vorrichtung die darin angeordnete Flüssigkeitsprobe umfasst, wobei optional die Flüssigkeitsprobe Urin oder zumindest eine flüssige Komponente von Blut umfasst.
  12. Pumpe nach einem der Ansprüche 5-11, wobei der Aktuator (50) dazu ausgelegt ist, eine Durchflussrate der Flüssigkeitsprobe innerhalb des Mikrokanals (1, 40) der mikrofluidischen Vorrichtung von mindestens etwa 1 nl/s, mindestens etwa 5 nl/s, mindestens etwa 10 nl/s, mindestens etwa 25 nl/s, mindestens etwa 50 nl/s, mindestens etwa 100 nl/s, mindestens etwa 250 nl/s, mindestens etwa 500 nl/s, mindestens etwa 1000 nl/s bereitzustellen und/oder wobei der Aktuator (50) dazu ausgelegt ist, eine Durchflussrate der Flüssigkeitsprobe innerhalb des Mikrokanals (1, 40) der mikrofluidischen Vorrichtung von etwa 10.000 nl/s oder weniger, etwa 5.000 nl/s oder weniger, etwa 2.500 nl/s oder weniger, zumindest etwa 1000 nl/s oder weniger bereitzustellen.
  13. Pumpe nach einem der Ansprüche 5-12, wobei ein Gesamtvolumen der Flüssigkeitsprobe innerhalb des Mikrokanals (1, 40) etwa 100 Mikroliter oder weniger, etwa 50 Mikroliter oder weniger, etwa 25 Mikroliter oder weniger, etwa 20 Mikroliter oder weniger ist.
  14. Pumpe nach einem der vorhergehenden Ansprüche, wobei der Kanal einen nicht eingedrückten Bereich umfasst und wobei, wenn durch den Aktuator (50) eingedrückt, der eingedrückte Teil des zweiten Substrats (10) mindestens etwa 50 %, mindestens etwa 75 %, mindestens etwa 90 %, mindestens etwa 95 %, mindestens etwa 97,5 %, mindestens etwa 99 % oder im Wesentlichen den gesamten nicht eingedrückten Bereich des Kanals bedeckt.
  15. Pumpe nach einem der vorhergehenden Ansprüche, wobei, im nicht eingedrückten Zustand, die Nut (1, 40) eine Breite hat, und wobei die Breite mindestens etwa 50 Mikrometer, mindestens etwa 100 Mikrometer, mindestens etwa 200 Mikrometer, mindestens etwa 500 Mikrometer ist, wobei optional, im eingedrückten Zustand die Breite der Nut (1, 40) mindestens etwa 75 %, mindestens etwa 90 %, mindestens etwa 95 %, mindestens etwa 97,5 %, mindestens etwa 99 % oder im Wesentlichen die gleiche wie im nicht eingedrückten Zustand ist.
  16. Pumpe nach einem der vorhergehenden Ansprüche, wobei, im eingedrückten Zustand, die Nut (1, 40) eine Breite hat, und wobei die Breite etwa 2000 Mikrometer oder weniger, etwa 1500 Mikrometer oder weniger, etwa 1000 Mikrometer oder weniger, etwa 750 Mikrometer oder weniger, etwa 600 Mikrometer oder weniger ist, wobei optional, im eingedrückten Zustand die Höhe der Nut (1, 40) mindestens etwa 75 %, mindestens etwa 90 %, mindestens etwa 95 %, mindestens etwa 97,5 %, mindestens etwa 99 % oder im Wesentlichen die gleiche wie im nicht eingedrückten Zustand ist.
  17. Pumpe nach einem der vorhergehenden Ansprüche, wobei, im nicht eingedrückten Zustand, das zweite Substrat (10) eine erste Dicke hat, die über der Nut (1, 40) liegt, und eine zweite Dicke hat, die lateral um einen ersten Abstand von der Nut (1, 40) beabstandet ist und wobei die zweite Dicke mindestens etwa 110 %, mindestens etwa 125 %, mindestens etwa 150 %, mindestens etwa 175 % oder mindestens etwa 200 % größer als die erste Dicke ist, wobei optional der erste Abstand etwa 50 % größer als eine Breite der Nut (1, 40), etwa 75 % größer als eine Breite der Nut (1, 40), etwa 100 % größer als eine Breite der Nut (1, 40), etwa 200 % größer als eine Breite der Nut (1, 40) ist.
EP13767323.2A 2012-03-26 2013-03-15 Mikrofluidische pumpe Active EP2847465B1 (de)

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US201261615786P 2012-03-26 2012-03-26
PCT/US2013/032020 WO2013148312A1 (en) 2012-03-26 2013-03-15 Microfluidic pump

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WO2021144396A1 (en) 2020-01-17 2021-07-22 F. Hoffmann-La Roche Ag Microfluidic device and method for automated split-pool synthesis
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EP2847465A4 (de) 2016-04-06
CN104204523A (zh) 2014-12-10
US20150050172A1 (en) 2015-02-19
EP2847465A1 (de) 2015-03-18
WO2013148312A1 (en) 2013-10-03
HK1208256A1 (en) 2016-02-26

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