BOEBETANECK HORST (DE)
| US20060166357A1 | 2006-07-27 | |||
| US20050191196A1 | 2005-09-01 | |||
| US20070207041A1 | 2007-09-06 | |||
| US20090245017A1 | 2009-10-01 | |||
| US20090054264A1 | 2009-02-26 | |||
| US20110200802A1 | 2011-08-18 | |||
| US4673657A | 1987-06-16 | |||
| US20060216212A1 | 2006-09-28 | |||
| US4131399A | 1978-12-26 | |||
| US20030026719A1 | 2003-02-06 | |||
| US20060042071A1 | 2006-03-02 |
| What is claimed is: 1. A pump, comprising: a channel 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. 2. The pump of claim 1, wherein the actuator is configured to translate along an axis of the groove. 3. The pump of claim 1 or claim 2, wherein 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. 4. The pump of any of the foregoing claims, 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. 5. The pump of any of the foregoing claims, wherein the first and second substrates are substantially planar. 6. The pump of any of the foregoing claims, wherein 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. 7. The pump of any of the foregoing claims, 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. 8. The pump of any of the foregoing claims, wherein the pump is disposed in fluidic communication with a microfluidic device. 9. The pump of claim 8, wherein the microfluidic device 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. 10. The pump of claim 9, wherein 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. 11. The pump of claim 10, wherein a proximal gas-liquid interface of the liquid sample is exposed to an ambient atmosphere. 12. The pump of any of claims 10-11, wherein the gas pressure acting upon the distal gas- liquid interface of the liquid sample is less than an ambient gas pressure. 13. The pump of any of claims 8-12, wherein the first and second substrates are disposed within the microfluidic device. 14. The pump of any of claims 9-13, wherein the microchannel of the microfluidic device comprises the liquid sample disposed therein. 15. The pump of claim 14, wherein the liquid sample comprises urine or at least one liquid component of blood. 16. The pump of any of claims 9-15, wherein 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. 17. The pump of any of claims 9-16, 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. 18. The pump of any of claims 9-17, wherein a total volume of liquid sample within the microchannel is about 100 microliters or less, about 50 microliters or less, about 25 microliters or less, about 20 microliters or less. 19. The pump of any of the foregoing claims, wherein 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. 20. The pump of any of the foregoing claims, wherein in the uncompressed state, the groove 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. 21. The pump of claim 20, 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. 22. The pump of any of the foregoing claims, wherein, in the compressed state, the groove 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. 23. The pump of claim 22, 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. 24. The pump of any of the foregoing claims, wherein, in the uncompressed state, the second substrate 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. 25. The pump of claim 24, 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. 26. A method, comprising: compressing at least a portion of a second surface of a second substrate into a groove in a first surface of a first substrate without substantially deforming the groove, wherein the compression occludes at least a portion of a channel defined by the second surface of the second substrate and the groove. 27. The method of claim 26, further comprising compressing different portions of the second surface, the different portions being offset from one another along an axis of the groove. 28. The method of claim 26 or claim 27, wherein 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. 29. The method of any of claims 26-29, 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. 30. The method of any of claims 26-29, wherein the first and second substrates are substantially planar. 31. The method of any of claims 26-30, wherein 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. 32. The method of any of claims 26-31 , 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. 33. The method of any of claims 26-32, further comprising introducing a liquid sample to a microchannel of a microfluidic device, the microchannel being in fluidic communication with the channel defined by the first and second substrates. 34. The method of claim 33, wherein the microchannel comprises at least one reagent for use in determining the presence of the at least one target. 35. The method of any of claims 33-34, wherein the compression produces a gas pressure acting upon a distal gas-liquid interface of the liquid sample disposed within the microchannel of the microfluidic device. 36. The method of claim 35, wherein a proximal gas-liquid interface of the liquid sample is exposed to an ambient atmosphere during the step of compressing. 37. The method of claim 35 or claim 36, wherein the gas pressure acting upon the distal gas-liquid interface of the liquid sample is less than an ambient gas pressure. 38. The method of any of claims 26-37, wherein the first and second substrates are disposed within the microfluidic device and the method comprises placing in the microfluidic device in an operable relationship with a reader having an actuator configured to perform the step of compression. 39. The method of claim 38, further comprising introducing a liquid sample to a microchannel of the microfluidic device and operating the reader to determine the presence of at least one target contained within the microfluidic device. 40. The method of claim 39, wherein the liquid sample comprises urine or at least one liquid component of blood. 41. The method of any of claims 26-40, wherein the step of compressing provides 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. 42. The method of any of claims 26-41, wherein the step of compressing provides a flow rate 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. 43. The method of any of claims 26-42, wherein a total volume of liquid sample within the microchannel is about 100 microliters or less, about 50 microliters or less, about 25 microliters or less, about 20 microliters or less. 44. The method of any of claims 26-43, wherein the channel has an uncompressed area and, during the step of compressing, 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. 45. The method of any of claims 26-44, wherein, in the uncompressed state, the groove 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. 46. The method of claim 45, 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%o, or essentially the same as in the uncompressed state. 47. The method of any of claims 26-46, wherein, in the compressed state, the groove 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. 48. The method of claim 47, 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%o, or essentially the same as in the uncompressed state. 49. The method of any of claims 26-48, wherein, in the uncompressed state, the second substrate has a first thickness overlying the groove and a second thickness spaced apart laterally a first distance from the groove and wherein the first 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 second thickness. 50. The method of claim 49, 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. 51. A microf uidic pump module, comprising: a first substrate and a second substrate, wherein the first substrate is formed from a material having a Shore A hardness of between about 25 and 70 and the second substrate is formed from a material having a Shore D hardness of between about 80 and 90, the second substrate comprising at least one microchannel formed on a surface thereof, and wherein the first and second substrates are joined so as to form a capillary. 52. The microfluidic pump module of claim 51 , wherein the at least one microchannel comprises a portion of its length that extends arcuately or linearly. 53. The microfluidic pump module of claim 52, wherein the at least one microchannel comprises a portion of its length that defines a generally circular or spiral flow path. 54. The microfluidic pump module of claim 53, wherein the circular or spiral portion has a length of between 20 to 100 mm. 55. The microfluidic pump module of any of claims 51-54, wherein the at least one microchannel has a length dimension of at least about 10mm, at least about 25 mm, at least about 50mm, at least about 100mm, at least about 200mm. 56. The microfluidic pump module of any of claims 51-55, wherein the at least one microchannel has a width dimension along all or a portion of its length of at least about lOOOum, at least about 900um, at least about 800um, at least about 700um, at least about 600um, at least about 500um and at least about 400um. 57. The microfluidic pump module of any of claims 51-56, wherein the at least one microchannel has a depth dimension along all or a portion of its length of at least about lOum, at least about 20um, at least about 30um, at least about 40um, at least about 50um and at least about lOOum. 58. The microfluidic pump module of any preceding claim, wherein the at least one microchannel has an arced, circular, elliptical or U shaped profile. 59. The microfluidic pump module of any of claims 51-58, wherein the at least one microchannel has an arced shaped profile having a radius of curvature of at least about 0.5mm, of at least about 0.6mm, of at least about 0.7mm, of at least about 0.8mm, of at least about 0.9mm and of least about 1mm. 60. The microfluidic pump module of any preceding claim, wherein the rate of flow of fluid within the microchannel can be controlled at a rate of between about 0.001 μΐ/s to about 5.0 μΐ/s. 61. The microfluidic pump module of any preceding claim, wherein the rate of flow of fluid within the microchannel can be controlled at a rate of about 0.001 μΐ/s, at a rate of about 0.002 μΐ/s, at a rate of about 0.004 μΐ/s, at a rate of about 0.008 μΐ/s, at a rate of about 0.01 μΐ/s, at a rate of about 0.02 μΐ/s, at a rate of about 0.05 μΐ/s, at a rate of about 0.075 μΐ/s, at a rate of about 0.1 μΐ/s, at a rate of about 0.2 μΐ/s, at a rate of about 0.3 μΐ/s, at a rate of about 0.5 μΐ/s, at a rate of about 0.75 μΐ/s, at a rate of about 1 μΐ/s, at a rate of about 1.5 μΐ/s, at a rate of about 2 μΐ/s, at a rate of about 3 μΐ/s, at a rate of about 4 μΐ/s, at a rate of about 5.0 μΐ/s. 62. The microfluidic pump module of any of claims 51-61, wherein the first plate element comprises an increased cross-sectional thickness which coincides with the microchannel on the surface of the second plate element. 63. The microfluidic pump module of claim 62, wherein the increased cross-sectional thickness is configured as a bump or ridge formed on the first plate element, and wherein further the bump has a width of between 700 to 1400 microns and a height of between 40 to 150 microns. 64. The microfluidic pump module of claim 63, wherein a raised surface of the bump has a radius of curvature of between 0.7 to 1.0 mm. 65. The microfluidic pump module of claim 64, wherein the increased cross-sectional thickness extends along all or a portion of the length of the microchannel. 66. The micro fluidic pump module of claim 65, wherein the cross-sectional area of the increased cross-sectional thickness is greater than the cross-sectional area of the microchannel with which it coincides. 67. The micro fluidic pump module of claim 51 , further comprising a deformation element rotatably engaged to the first plate element and configured to deform a portion of the first plate element into the microchannel on the surface of the second plate element. 68. The micro fluidic pump module of claim 61, further comprising a deformation element rotatably engaged to the first plate element and configured to deform the increased cross- sectional thickness of the first plate element into the microchannel on the surface of the second plate element. 69. The microfluidic pump module of claims 68, wherein the deformation element is configured to deform the portion of, or the increased cross-sectional thickness of, the first plate element into the microchannel incrementally along a length of the microchannel thereby advancing fluid along the length of the microchannel. 70. The microfluidic pump module of claim 67, wherein the deformation element is a cylindrical roller having an outside surface which rotatably engages the first plate element, and wherein the cylindrical roller has a greater hardness than the first plate element. 71. The microfluidic pump module of claim 70, further comprising at least two cylindrical rollers disposed to rotatably engage the first plate. 72. The microfluidic pump module of claim 51 , further comprising at least one additional microchannel formed on the surface of the second plate element. 73. The microfluidic pump module of claim 72, wherein at least two microchannels are disposed adjacent one another as concentric arcs, rings or spirals. 74. The micro fluidic pump module of claim 73, wherein each microchannel has a different cross-sectional area. 75. The micro fluidic pump module of claim 71, wherein the first and second plate elements have a thickness of between 40 to 100 microns. 76. The micro fluidic pump module of any of claims 51-75, wherein the first and second plate elements are coupled via an adhesive. 77. The microfluidic pump module of claim 76, wherein the adhesive comprises a UV curable adhesive, a heat cured adhesive, a pressure sensitive adhesive, an oxygen sensitive adhesive, a double-sided tape adhesive. 78. The microfluidic pump module of any of claims 51-77, wherein the first and second plate elements are coupled via a welding process. 79. The microfluidic pump module of claim 78, wherein the welding process comprises an ultrasonic welding process, a laser welding process, a thermal welding process, a torsional welding process. 80. The microfluidic pump module of any of claims 51-79, wherein the first and second plate elements are coupled via a laser welding process, the process comprising: (a) exposing one of the first or second plate elements to ultra violet laser energy around the periphery of the microchannel so as to carbonize the surface of the first or second plate element; (b) applying a compressive force between the first and second plate elements; and (c) exposing the compressed first and second plate elements to infra red laser energy to cause localized heating and melting in the proximity of the carbonized surface of (a) so as to seal the first and second plate elements, thereby forming the fluid tight seal along the boundary of the microchannel. 81. A micro fluidic device, comprising; (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. 82. The micro fluidic device of claim 81, further comprising a fluid tight seal formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary. 83. The microfluidic device of claim 82, wherein the raised element is a bump. 84. The microfluidic device of claim 83, wherein the bump has a width of between 700 to 1400 microns and a height of between 40 to 150 microns. 85. The microfluidic device of claim 84, wherein a raised surface of the bump has a radius of curvature of between 0.7 to 1.0 mm. 86. The microfluidic device of claim 81, wherein the microchannel has a width dimension of between 500 to 900 microns and a depth dimension of between 40 to 100 microns. 87. The microfluidic device of claim 81, wherein the microchannel has an arced, circular, elliptical or U shaped bottom. 88. The microfluidic device of claim 87, wherein the microchannel has an arced shaped bottom having a radius of curvature of between 0.7 and 0.9 mm. 89. The microfluidic device of claim 82, wherein the capillary is configured for a flow rate within the capillary of between 0.001 μΐ/s to 5.0 μΐ/s. 90. The micro fluidic device of claim 81, wherein the microchannel comprises a portion of its length that extends arcuately. 91. The micro fluidic device of claim 90, wherein the arced portion defines a generally circular or spiral flow path. 92. The micro fluidic device of claim 91, wherein the arced portion has a length of between 20 to 100 mm. 93. The micro fluidic device of claim 90, wherein the microchannel further comprises a portion of its length that extends linearly. 94. The micro fluidic device of claim 93, wherein the linear portion has a length dimension of between 0.5 to 10 cm. 95. The micro fluidic device of claim 93, wherein the microchannel comprises at least two portions of its length that extend linearly. 96. The micro fluidic device of claim 81, further comprising at least one additional microchannel formed on the surface of the rigid substrate. 97. The microfluidic device of claim 96, wherein at least two microchannels having arcuate portions are disposed adjacent one another on the surface of the rigid substrate, the arcuate portions being disposed as concentric arcs, rings or spirals. 98. The microfluidic device of claim 97, wherein each microchannel has a different cross- sectional area. 99. The microfluidic device of claim 81, wherein the rigid substrate and the flexible layer each have a thickness of between 40 to 100 microns. 100. The micro fluidic device of claim 81, wherein the rigid substrate and the flexible layer are coupled via an adhesive. 101. The micro fluidic device of claim 100, wherein the adhesive comprises a UV curable adhesive, a heat cured adhesive, a pressure sensitive adhesive, an oxygen sensitive adhesive, a double-sided tape adhesive. 102. The microfluidic device of claim 100, wherein the rigid substrate and the flexible layer are coupled via a welding process. 103. The microfluidic device of claim 102, wherein the welding process comprises an ultrasonic welding process, a laser welding process, a thermal welding process, a torsional welding process. 104. The microfluidic device of claim 103, wherein the rigid substrate and the flexible layer are coupled via a laser welding process, the process comprising: (a) exposing one of the rigid substrate or the flexible layer to ultra violet laser energy around the periphery of the microchannel so as to carbonize the surface of the rigid substrate or the flexible layer; (b) applying a compressive force between the rigid substrate and the flexible layer; and (c) exposing the compressed rigid substrate and the flexible layer to infra red laser energy to cause localized heating and melting in the proximity of the carbonized surface of (a) so as to seal the rigid substrate and the flexible layer, thereby forming a fluid tight seal along the boundary of the microchannel. 105. A method for performing a microfluidic process, comprising: (a) applying a voltage to a microfluidic pump module, the microfluidic pump module comprising: (i) a first plate element coupled to a second plate element, wherein the first plate element is elastomeric and the second plate element is non- elastomeric, the second plate element comprising a microchannel formed on a surface of the second plate element, and the first plate element comprises a raised element disposed over a portion or all of the microchannel, and wherein further 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; and (ii) a deformation element rotatably engaged to the first plate element and configured to advance along a length of the microchannel upon application of the voltage; (b) allowing the deformation element to advance along the length of the microchannel, wherein advancement of the deformation element causes the raised element to deform into the microchannel, thereby forcing a fluid within the microchannel to flow along the fluid flow path. 106. The method of claim 105, wherein the deformation element is a cylindrical roller having an outside surface which rotatably engages the raised element, and wherein the cylindrical roller has a greater hardness than the raised element. 107. The method of claim 106, wherein the microf uidic pump further comprises at least two cylindrical rollers disposed to rotatably engage one or more raised elements disposed over the microchannel. 108. The method of claim 105, wherein the microfluidic pump is adapted for a flow rate within the microchannel of between 0.001 μΐ/s to 5.0 μΐ/s. 109. The method of claim 105, further comprising reversing the direction of the deformation element thereby reversing the direction of fluid flow within the microchannel. 110. The method of claim 105, wherein the microchannel comprises a portion of its length that extends arcuately. 111. The method of claim 110, wherein the microchannel comprises a portion of its length that defines a generally circular or spiral flow path. 112. The method of claim 105, wherein the micro fluidic pump further comprises at least one additional microchannel formed on the surface of the second plate element. 113. The method of claim 112, wherein at least two microchannels are disposed adjacent one another as concentric arcs, rings or spirals. 114. The method of claim 113, wherein each microchannel has a different cross-sectional area. 115. The method of claim 105, further comprising detecting an analyte or biological reaction in the fluid. 116. A method of manufacturing a micro fluidic device, comprising: coupling a rigid substrate having a microchannel formed on a surface thereof, to a flexible layer overlying the rigid substrate and enclosing the microchannel, wherein a fluid tight seal is formed between the rigid substrate and the flexible layers along a periphery of the microchannel forming an enclosed capillary, and wherein the rigid substrate and the flexible layer are coupled via a laser welding process, the process comprising: (a) exposing one of the rigid substrate or the flexible layer to ultra violet laser energy around the periphery of the microchannel so as to carbonize the surface of the rigid substrate or the flexible layer; (b) applying a compressive force between the rigid substrate and the flexible layer; and (c) exposing the compressed rigid substrate and the flexible layer to infra red laser energy to cause localized heating and melting in the proximity of the carbonized surface of (a) so as to seal the rigid substrate and the flexible layer, thereby forming a fluid tight seal along the boundary of the microchannel. 117. The pump of any of claims 1-25, wherein the first and second substrates are joined by a laser welding process. 118. A method of manufacturing any pump of any of claims 1-26, comprising joining the first and second pumps by a process that includes irradiating a portion of the first and second substrates with light from a laser. 119. The pump of any of claims 1-25, wherein, in the uncompressed state, the second surface of the second substrate is substantially planar. 120. The method of any of claims 26-50, wherein, in the uncompressed state, the second surface of the second substrate is substantially planar. 121. The pump of any of claims 1-25, wherein the groove is concave, triangular, square, or rectangular. 122. The pump of any of claims 1-25, wherein the groove has a long axis and the actuator is configured to translate along the long axis of the groove. 123. The pump of claim 122, wherein the pump is configured to translate a distance along the long axis of the groove sufficient to pump a volume of at least about 500 nl, at least about 1 microliter, at least about 2.5 microliters, at least about 5 microliters, at least about 10 microliters, at least about 20 microliters. 124. The pump of claim 122, wherein the pump has a capacity to pump a total volume of about 10 ml or less, about 5 ml or less, about 2.5 ml or less, about 1 ml or less, or about 0.5 ml or less. 125. The pump of any of claims 1-25 or 121-124, wherein the actuator is configured to compress a portion of the second substrate into the groove, simultaneously or sequentially, along a distance of at least about 1 mm, at least about 2.5 mm, at least about 5 mm, at least about 10 mm, at least about 20 mm, or at least about 50 mm. 126. The pump of any of claims 1-25 or 121-125, wherein the actuator is configured to compress a portion of the second substrate into the groove, simultaneously or sequentially, along a distance of about 100 mm or less, about 75 mm or less, about 50 mm or less. 127. The pump of any of claims 1-25 or 121-126, wherein the actuator is configured to translate a position of compression along a long axis of the groove. 128. The pump of any of claims 1-25 or 121-127, wherein the actuator is configured to compress, at any given time, only a single portion of the second substrate into the groove. 129. The pump of claim 128, wherein the actuator is configured to translate the single compressed portion of the second substrate along at least a portion of the groove, selected from at least about 25% of a length of the groove, at least about 35% of a length of the groove, at least about 50%> of a length of the groove, at least about 75% of a length of the groove. 130. The pump of any of claims 1-25 or 121-129, wherein the portion of the second substrate that is compressed into the groove at any one time has a length along the groove that is less than about 50%, less than about 30%>, less than about 25%, less than about 20%, less than about 15%, less than about 10% of a total length of the groove. 131. The method of any of claims 26-50 and 120, wherein the groove is convex, triangular, square, or rectangular. 132. The method of any of claims 26-50, 120, and 131, wherein the groove has a long axis and the step of compressing comprises translating the actuator along at least a portion of the long axis of the groove. 133. The method of any of claims 26-50, 120, and 131-132, wherein the step of compressing comprises compressing, simultaneously or sequentially, a sufficient length of the groove to pump a volume of at least about 500 nl, at least about 1 microliter, at least about 2.5 microliters, at least about 5 microliters, at least about 10 microliters, at least about 20 microliters. 134. The method of any of claims 26-50, 120, and 131-133, wherein the step of compressing comprises compressing, simultaneously or sequentially, a length of the groove sufficient to pump a total volume of about 10 ml or less, about 5 ml or less, about 2.5 ml or less, about 1 ml or less, or about 0.5 ml or less. 135. The method of any of claims 26-50, 120, and 131-134, wherein the step of compressing comprises compressing the groove along a distance of at least about 1 mm, at least about 2.5 mm, at least about 5 mm, at least about 10 mm, at least about 20 mm, or at least about 50 mm of the groove. 136. The pump of any of claims 1-25 or 121-125, wherein the actuator is configured to compress the groove along a distance of about 100 mm or less, about 75 mm or less, about 50 mm or less. 137. The pump of any of claims 1-25 or 121-126, wherein the actuator is configured to translate a position of compression along a long axis of the groove. 138. The pump of any of claims 1-25 or 121-127, wherein the actuator is configured to compress, at any given time, only a single portion of the second substrate into the groove. 139. The pump of claim 128, wherein the actuator is configured to translate the single compressed portion of the second substrate along at least a portion of the groove, selected from at least about 25% of a length of the groove, at least about 35% of a length of the groove, at least about 50%> of a length of the groove, at least about 75% of a length of the groove. 140. The pump of any of claims 1-25 or 121-129, wherein the portion of the second substrate that is compressed into the groove has a length along the groove that is less than about 50%, less than about 30%>, less than about 25%, less than about 20%>, less than about 15%, less than about 10% of a total length of the groove. 141. The pump of any preceding claim, wherein two or more grooves are provided in the first substrate, thereby defining at least two discrete channels. 142. The pump of claim 141, wherein the at least two discrete channels have a width wl, and a width w2, wherein width wl is at least about 75% w2, at least about 90%> w2, at least about 95%o w2, at least about 97.5%> w2, at least about 99%> w2, or essentially the same as w2. 143. The pump of claim 141-142, wherein the at least two discrete channels have a height hi, and a height h2, wherein height hi is at least about 75% h2, at least about 90% h2, at least about 95% h2, at least about 97.5% h2, at least about 99% h2, or essentially the same as h2. 144. The pump of claims 141-143, wherein the at least two discrete channels have a cross sectional area al, and a cross sectional area a2, wherein al is at least about 75% a2, at least about 90%) a2, at least about 95%> a2, at least about 97.5%> a2, at least about 99%> a2, or essentially the same as a2. 145. The pump of claims 141-144, wherein the at least two discrete channels are substantially parallel, and concentric. 146. The pump of claim 145, wherein at least one channel has a radius rl, and at least another channel has a radius r2, wherein rl is greater than r2. 147. The pump of claim 146, wherein radius rl , is about 1.25 times radius r2, is about 1.5 times r2, is about 2 times r2, is about 3 times r2, is about 5 times r2, is about 10 times r2. 148. The pump of claims 141-147, wherein when said actuator rotates about a point concentric to the at least two discrete channels, a portion of said second substrate is compressed into said groove. 149. The pump of claim 148, wherein the actuator is cylindrical. 150. The pump of claims 148-149, wherein the actuator comprises at least one element that rotates on an axle substantially parallel to the (top) surface of the first substrate. 151. The pump of claims 149-150, wherein the actuator comprises at least one, at least two, at least three, at least four, at least five independent members along an axle. 152. The pump of claim 148, wherein the actuator is conical. 153. The pump of claims 148-152, wherein the conical actuator has a radius rl at the narrow end and a radius r2 at the wide end. 154. The pump of claims 148 or 152-153, wherein the conical actuator rotates on an axle nonparallel to the surface of the first and second substrate. 155. The pump of claims 148 or 152-154, wherein the conical actuator applies a compressive force above to the second substrate at least above the at least two discrete channels. 156. The pump of claims 149-155, wherein the conical actuator has a straight edge profile. 157. The pump of claims 149-156, wherein the conical actuator has an edge profile comprising one or more raised features which co-align with the one or more grooves in the first substrate. 158. The pump of claim 144, wherein the cross sectional area al is about 1.25 times the cross sectional area a2, is about 1.5 times the cross sectional area a2, is about 1.75 times the cross sectional area a2, is about 2 times the cross sectional area a2, is about 4 times the cross sectional area a2, is 6 times the cross sectional area a2, or is 10 times the cross sectional area a2. 159. The pump of claim 144, wherein a volume of fluid is dispensed by the at least two discrete channels, vl, v2, for each complete revolution of the actuator, wherein volume vl is at least about 75% v2, at least about 90% v2, at least about 95%> v2, at least about 97.5%> v2, at least about 99% v2, or essentially the same as v2. 160. The pump of claim 144, wherein a volume of fluid is dispensed by the at least two discrete channels, vl, v2, for each complete revolution of the actuator, wherein volume vl is at least 2 fold volume v2, at least 3 fold volume v2, at least 5 fold volume v2, at least 10 fold volume v2, at least 25 fold volume v2, at least 50 fold volume v2, at least 100 fold volume v2. 161. A micro fluidic device, comprising; at least one pump according to claim 1 or claim 144; a series of microfluidic channels in communication with the at least one pump; at least one sample application zone; a detection zone; and a waste collection zone. 162. A microfluidic pump module comprising; (a) a first substrate, comprising a major surface defining a groove thereon; (b) a second substrate, wherein said second substrate operates with said first substrate, to enclose the groove to form a microchannel; and (c) an actuator configured to apply a force to the second substrate; characterized in that when a force is applied to the second substrate, a portion of the second substrate occludes the groove, and in doing so the dimensions of the groove are not substantially changed. 163. The micro fluidic pump module of claim 162, wherein the second substrate has a Shore D hardness of between about 80D and about 90D 164. The micro fluidic pump module of claim 162 or claim 163, wherein the second substrate has a Shore A hardness of between about 35 A and about 55 A 165. The micro fluidic pump module of claims 162-164, wherein when the actuator forces the second substrate into the grooves of the first substrate, the width w of the groove is at least about 75%, at least about 80%>, at least about 85%, at least about 90%>, at least about 95%), at least about 97.5%, at least about 99% at least about 99.9%, or is essentially the same as the groove absent the presence of second substrate. 166. The microfluidic pump module of claims 162-165, wherein when the actuator forces the second substrate into the grooves of the first substrate, the height h of the groove is at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%o, at least about 97.5%, at least about 99% at least about 99.9%, or is essentially the same as the groove absent the presence of second substrate. 167. The microfluidic pump of any preceding claim wherein the first substrate is selected from one of, but is not limited to, polystyrene, polypropylene, polymethylmethacrylate, polycarbonate, or the like. |
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
[0001] The invention relates to micro fluidics technology, and more particularly to a microfiuidic pump for control of fluid flow through microchannels.
BACKGROUND INFORMATION
[0002] Microfluidics systems are of significant value for acquiring and analyzing chemical and biological information using very small volumes of liquid. Use of microfiuidic 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 microfiuidic volumes also enhances safety and reduces disposal quantities.
[0003] Microfiuidic 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.
[0004] The microcomponents required for these ends are often complex and costly to produce. For example, a 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 microfiuidic device, or achieving complex fluid flow patterns inside microfiuidic channels is difficult.
SUMMARY OF THE INVENTION
[0005] A microfiuidic pump has been developed in order to provide low cost, high accuracy means for onboard sample handling in disposable assay devices. Devices utilizing the microfiuidic pump, as well as methods for manufacture and performing a microfiuidic process are also provided. [0006] Accordingly, in one aspect, the present invention provides a microfiuidic pump module. In one embodiment, the microfiuidic pump module includes 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.
[0007] In another aspect, the invention provides a microfiuidic device utilizing the microfiuidic pump module described herein. The microfiuidic 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.
[0008] In another aspect, the invention provides a microfiuidic device utilizing the microfiuidic pump module described herein. The microfiuidic 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.
[0009] In a further aspect, the invention provides a microfiuidic device utilizing the microfiuidic 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. In some
embodiments the microchannels have identical cross sectional areas, such that the volume of fluid transported per unit distance of the microchannel is substantially the same. In other embodiments the at least two microchannels have different cross sectional areas, in which instance the volume of fluid transported per unit distance of the microchannel is different. [0010] In still a further aspect, the invention provides a micro fluidic device utilizing the microfluidic pump module described herein, wherein the pump module comprises at least two independent microchannels arranged concentrically about a point upon which at least one actuator rotates. In such embodiment where the at least two microchannels have identical cross sectional area, per revolution of the at least one actuator, a greater volume of fluid will be transported in the outermost channel according to the equation Q = rcoA, where Q is the volume flow rate, r is the radius of the microchannel, ω is the angular velocity and A is the cross sectional area of the microchannel. Thus if the outermost channel has a radius r2, which is three times the radius of the inner most channel rl, then three times the volume of fluid will be transported in the outermost channel compared with the innermost channel per revolution of the actuator. The skilled person will thus readily recognize that by altering the relative ratio of cross sectional area of the respective concentric microchannels, different volumes of fluid may be transported per revolution in each respective channel
[0011] In another aspect, the invention provides a method for performing a microfluidic process. 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%o, 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. 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.
[0012] In another aspect, the invention provides a method of manufacturing a microfluidic device. 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:
(a) exposing one of the rigid substrate or the flexible layer to ultra violet laser energy around the periphery of the microchannel so as to carbonize the surface of the rigid substrate or the flexible layer;
(b) applying a compressive force between the rigid substrate and the flexible layer; and
(c) exposing the compressed rigid substrate and the flexible layer to infra red laser energy to cause localized heating and melting in the proximity of the carbonized surface of (a) so as to seal the rigid substrate and the flexible layer, thereby forming a fluid tight seal along the boundary of the microchannel.
[0013] In another aspect the invention provides a method of manufacturing a microfluidic device. 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) injecting a first polymer composition into an injection mold cavity to form the rigid substrate;
(b) injecting a second polymer composition into an injection mold cavity to form the flexible layer; and
(c) causing the molten second polymeric material to fuse with the first polymeric material introduced in (a) so as to seal the rigid substrate and the flexible layer, thereby forming a fluid tight seal along the boundary of the microchannel.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Figure 1 is a series of schematics illustrating movement of various components during operation of a microfluidic device in embodiments of the invention.
[0015] Figure 1 A is a cross-sectional view of a portion of a microfluidic device in embodiments of the invention.
[0016] Figure IB is a cross-sectional view of a portion of a microfluidic device in embodiments of the invention.
[0017] Figure 2 is a cross-sectional view of a portion of a microfluidic device in embodiments of the invention.
[0018] Figure 3 is a perspective view of a portion of a microfluidic device in an embodiment of the invention.
[0019] Figure 4 is a top view of a portion of a microfluidic device in an embodiment of the invention.
[0020] Figure 5 is a perspective view of a microfluidic device in an embodiment of the invention.
[0021] Figure 6 is a series of schematics illustrating a microfluidic device in embodiments of the invention. [0022] Figure 6A is a top view of a microfluidic device in an embodiment of the invention.
[0023] Figure 6B is a top view of a microfluidic device in an embodiment of the invention.
[0024] Figure 6C is a top view of a microfluidic device in an embodiment of the invention.
[0025] Figure 7 is a graphical representation depicting data generated with a microfluidic device in an embodiment of the invention.
[0026] Figure 8 is a graphical representation depicting data generated with a microfluidic device in an embodiment of the invention.
[0027] Figure 9 is a graphical representation depicting data generated with a microfluidic device in an embodiment of the invention.
[0028] Figure 10 is a top view of a portion of a microfluidic device in an embodiment of the invention.
[0029] Figure 11 is a cross-sectional schematic of a drive for use in one embodiment of the invention.
[0030] Figure 12 is a cross-sectional schematic of a drive for use in one embodiment of the invention.
[0031] Figure 13 is a top view schematic of a microfluidic device in an embodiment of the invention. DETAILED DESCRIPTION OF THE INVENTION
[0032] 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. Advantageously, the rate of fluid flow within the pump is essentially constant even at very low flow rates.
[0033] 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.
[0034] With reference to Figures 1 A and IB, one or more 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. When a force, for example via a deformation element such as roller (50), is applied to the elastomer material (10), at least of portion of the second substrate is compressed into the microchannel (40) of the non-elastomeric (20) component thereby occluding at least a portion of the microchannel (40) at the site of compression.
[0035] 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. For example, 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. In embodiments, 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.
[0036] The compression may create a fluid-tight seal between the first and second substrates within the groove at the site of compression. When a fluid-tight seal is formed, fluid, e.g., a liquid, is prevented from passing along the groove from one side of the site of compression to the other side of the site of compression.
[0037] 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.
[0038] The groove has a first cross-sectional area in an uncompressed state and a second cross-sectional area in the compressed state. In embodiments, the portion of the elastomer is compressed into the groove without substantially deforming the groove. For example, 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. In embodiments, 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. In embodiments, 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.
[0039] Translation of the site of compression along the length of the microchannel (40) creates an effective pumping action resulting in flow of fluid within the microchannel (40) in the direction of the advancing deformation element (50). In some embodiments 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). For example, in the uncompressed state, the elastomer may have a first thickness overlying the groove and a second thickness spaced apart laterally a first distance from the center of the groove. In embodiments, the second thickness is at least about 1 10%, 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.
[0040] 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.
[0041] In one aspect, a microfluidic pump module (100) is provided utilizing the microfluidic structure described herein. Again with reference to Figures 1A and IB, 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.
[0042] In another aspect, the invention provides a microfluidic device (100) utilizing the microfluidic pump module described herein. Again with reference to Figures 1A and IB, 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).
[0043] In yet a further aspect, the invention provides a microfluidic device (100), which again with reference to Figures 1A and IB, the reverse orientation is provided. In this instance 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. [0044] In various embodiments, 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. One skilled in the art would understand that the raised element (30) may be one of a number of suitable shapes such as a bump. In other embodiments, 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).
[0045] One or more microchannels (40) may be formed on a surface of the rigid substrate (20) by any number of suitable techniques known in the art. For example, 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.
[0046] 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. In one embodiment, a microchannel will have a constant width dimension and a constant depth dimension along a length of the microchannel which engages a deformation element. In general, a microchannel has a width dimension of between 500 to 900 microns and a depth dimension of between 40 to 100 microns. As such, the device may be adapted for a flow rate within the microchannel of between 0.001 μΐ/s to 5.0 μΐ/s.
[0047] Microchannels having a variety of cross-sectional geometries may be utilized. Figures 1 A and IB depict a microchannel (40) in which the bottom surface of the microchannel is arced and defines a concave circular geometry. However, it will be understood that the microchannel (40) may have a rounded, elliptical or generally U shaped bottom. In one embodiment, 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.
[0048] One skilled in the art would appreciate that the surfaces of microchannels (40) may be modified, for example by varying hydrophobicity. For instance, 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.
[0049] As discussed herein, 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. For example, 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. In one embodiment, the circular or spiral portion of the microchannel has a length of between 20 to 100 mm.
[0050] 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 (1 10) shown). As will be appreciated by those of skill in the art, the rotational direction of the deformation elements (50) with relation to the micro fluidic laminate structure (1 10) dictates the direction of flow within the microchannel. As such, one skilled in the art would appreciate that, advantageously, fluid flow through the pump may be bidirectional.
[0051] Housing (80) may be rotated by applying a voltage to a motor controlling movement thereof. As such, the invention further provides 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).
[0052] 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.
[0053] In one embodiment, between 100 and 10,000 pulses per second may be applied resulting in a flow rate of between 0.001 μΐ/s to 5.0 μΐ/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.
[0054] For example, 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 ano p nf rm1 « p ;s per second indicating substantially constant flow with minimal shear. [0055] Figures 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.
[0056] With reference to Figure 1 , as discussed herein, 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).
[0057] 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.
[0058] Alternatively, the parts may be coupled utilizing a welding process. Such processes including an ultrasonic welding process, a thermal welding process, and a torsional welding process.
[0059] In a further alternative, 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. One of skill in the art will readily appreciate that elastomeric and non-elastomeric polymers can be joined in this way to achieve fluid tight seals between the parts.
[0060] In one embodiment a process of laser welding is utilized. The process includes: (a) exposing one of the first or second plate elements to ultra violet laser energy around the periphery of the microchannel so as to carbonize the surface of the first or second plate element;
(b) applying a compressive force between the first and second plate elements; and
(c) exposing the compressed first and second plate elements to infra red laser energy to cause localized heating and melting in the proximity of the carbonized surface of (a) so as to seal the first and second plate elements, thereby forming a fluid tight seal along the boundary of the microchannel.
[0061] 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.
[0062] In various embodiments, additional microchannels and structures may be provided to allow the device to perform a number of different types of biological assays or reactions. For example, 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.
[0063] The following embodiment describes the use of a 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.
[0064] Two aspects are described. First, a very low cost method to perform pumping a liquid sample to stored dry chemicals which are deposited at a location internal to the consumable, followed by mixing of the liquid sample with the stored chemicals. Second, dilution of chemicals using the same active pumping system where the dilution step occurs part way through the diagnostic process. [0065] The two aspects may be used together or individually. They shall now be described separately with reference to Figures 11-13. Reference numerals for features of Figures 11-13 as used in this Example are specific for each Figure and may be represented by another numeral in Figures 1-10 of this application.
[0066] With reference to Figure 11 , 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.
[0067] By providing inlet and outlet ports to the mixing chamber from the pump microchannels, 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. A sequence of events is provided in Table 1 below.
[0068] 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 Pump rotor is disengaged and sample fluid remains in mixing clockwise 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.
[0069] 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. However, in this particular embodiment 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.
[0070] Located within this annular channel is one or many 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.
[0071] With reference to Figure 13 and including features of the motor drive system described in the sections above, the method to perform a dilution step during the diagnostic test using the circular or spiral peristaltic pump is described: 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.
[0072] Should more fluids be required to be pumped in separate channels, this peristaltic pump can be designed to accommodate multiple fluidic channels on different radii if desired. In this embodiment 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.
[0073] It is preferable to store the dilution fluid away from the stored chemicals so the stored chemicals do not become affected by the dilution fluid. When 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. When the motor stops both dilution fluid and sample fluid remain in their respective chambers.
[0074] If mixing is required, an equivalent mechanism as described above could be implemented which rotates the motor in the opposite direction to only provide mixing. When the sample fluid and dilution fluid are required to be combined, 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). To assist combining the two fluids, passive mixing features (10) may be included at the fluid combining region. As 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).
[0075] Several advantages are provided by the invention. First, manufacturing costs are lowered due to the function and form of the circular or spiral peristaltic pump design. Aspects of the pump design which make this possible are circular or spiral geometry allows for the use of only one actuator; in this embodiment it is an electric motor, such that rotating the motor in one direction performs a different function to rotating the motor in the opposite
Hi p rtinn A n additional feature of the pump design is the ability for the consumable part of the pump to include multiple pump channels such that multiple fluids may be transported using the same motor drive mechanism.
[0076] If a chemical reaction, such as an amplification reaction, is performed which could result in contamination, or if the potential for contamination is to be removed for other reasons, then the pump design allows the pump to be sealed to the environment.
[0077] 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.
[0078] Although the invention has been described it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims.
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