Microfluidic system comprising a cooling device

Abstract

A microfluidic system for isolating biological entities includes a cooling device including a thermoelectric heat pump, a first fan, and a first heat exchanger disposed between the first fan and the thermoelectric heat pump; a first housing structure having a first casing that encloses the first fan and the first heat exchanger; a microfluidic device and one or more piezoelectric transducers attached to the microfluidic device; and a second housing structure reversibly attached to the first housing structure and having a second casing that encloses the microfluidic device and the one or more piezoelectric transducers therein. When the first and second housing structures are coupled, a first air passageway is formed between a side of the first heat exchanger and an end of the microfluidic device, and a second air passageway is formed between the first fan and the piezoelectric transducers, allowing air to circulate between the first and second air passageways.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to provisional application No. 63 / 109,264, filed on November 3, 2020, the contents of which are incorporated herein by reference in their entirety. Background Technology

[0003] The present invention relates to an apparatus for separating biological entities suspended in a fluid, and more specifically, to an embodiment of a microfluidic system comprising a microfluidic device and a heat transfer device for cooling the microfluidic device.

[0004] Acoustic particle separation methods for extracting or separating various biological entities suspended in fluid samples (such as blood) have attracted significant attention in biological and biomedical applications. These methods utilize acoustic radiation pressure generated by a piezoelectric transducer attached to a microfluidic device to separate particles of different sizes or acoustic contrasts. Because relatively high power can be applied to the piezoelectric transducer during operation, the heat generated by the transducer can heat the fluid sample flowing through the microfluidic device and damage the biological entities within it. Therefore, the microfluidic device and / or the piezoelectric transducer require appropriate cooling during operation.

[0005] For the reasons mentioned above, there is a need for a compact cooling device that can reliably cool microfluidic devices during operation. Summary of the Invention

[0006] This invention aims to provide a device that meets this need. A microfluidic system for separating biological entities includes: a cooling device comprising a thermoelectric heat pump, a first fan, a first heat exchanger disposed between the first fan and the thermoelectric heat pump, a second fan, and a second heat exchanger disposed between the second fan and the thermoelectric heat pump; a first housing structure having a first shell surrounding the first fan and the first heat exchanger, the first housing structure having a first cavity and a second cavity respectively exposing both sides of the first heat exchanger, and a third cavity formed opposite to the first fan and the first heat exchanger; a microfluidic device and one or more piezoelectric transducers attached to the microfluidic device; and a second housing structure reversibly attached to the first housing structure and having a second shell therein enclosing the microfluidic device and the one or more piezoelectric transducers, the second housing structure including a fourth cavity, a fifth cavity, and a sixth cavity, the fourth and fifth cavities respectively exposing both ends of the microfluidic device. When the first housing structure and the second housing structure are connected, the first cavity and the second cavity are aligned with the fourth cavity and the fifth cavity, respectively, to form a first air passage and a second air passage between the two sides of the first heat exchanger and the two ends of the microfluidic device. The third cavity and the sixth cavity are aligned to form a third air passage between the first fan and one or more piezoelectric transducers, thereby allowing air to circulate between the third air passage and the first air passage and the second air passage.

[0007] According to another aspect of the invention, a microfluidic system for separating biological entities includes: a cooling device comprising a thermoelectric heat pump, a first fan and a first heat exchanger disposed between the first fan and the thermoelectric heat pump, a second fan and a second heat exchanger disposed between the second fan and the thermoelectric heat pump; a first housing structure having a first shell surrounding the first fan and the first heat exchanger, the first housing structure having a first cavity exposing a side of the first heat exchanger and a second cavity formed adjacent to the first fan and opposite to the first heat exchanger; a microfluidic device and one or more piezoelectric transducers attached to the microfluidic device; and a second housing structure reversibly attached to the first housing structure and having a second shell therein enclosing the microfluidic device and the one or more piezoelectric transducers, the second housing structure including a third cavity and a fourth cavity, the third cavity exposing an end of the microfluidic device. When the first housing structure and the second housing structure are coupled, the first cavity and the third cavity are aligned to form a first air passage between the side of the first heat exchanger and the end of the microfluidic device, and the second cavity and the fourth cavity are aligned to form a second air passage between the first fan and the one or more piezoelectric transducers, thereby allowing air to circulate between the first air passage and the second air passage. Attached Figure Description

[0008] These and other features, aspects, and advantages of the invention will become more readily understood from the following description, the accompanying claims, and the accompanying drawings, wherein:

[0009] Figure 1A This is a top view of a microfluidic device for separating biological entities according to an embodiment of the present invention;

[0010] Figure 1B and Figure 1C This is a cross-sectional view of a microfluidic device, showing the alternative location of the inlet port;

[0011] Figure 1D and Figure 1E This is a cross-sectional view of a microfluidic device at the upstream end of the fluid channel, illustrating an alternative location for attaching a piezoelectric transducer;

[0012] Figure 1F and Figure 1G This is a cross-sectional view of a microfluidic device at the downstream end of the fluid channel, illustrating an alternative location for attaching a piezoelectric transducer;

[0013] Figure 2 Example of microfluidic device operation under single pressure node conditions;

[0014] Figure 3 Examples of components of a cooling device for cooling a microfluidic device according to embodiments of the present invention;

[0015] Figure 4 This illustrates a structure partially enclosed by a lower housing structure according to an embodiment of the present invention. Figure 3 A cross-sectional view of the cooling device in the middle;

[0016] Figure 5 This is a cross-sectional view illustrating an upper housing structure according to an embodiment of the present invention, which can be reversibly attached to a lower housing structure;

[0017] Figure 6 An example is shown of the connection between the upper and lower shell structures, used to form a central air passage and two side air passages to allow air circulation between them;

[0018] Figure 7 This is an example Figure 6 A cross-sectional view of an alternative arrangement of the microfluidic device and heating element in the upper housing structure shown.

[0019] Figure 8 This is a cross-sectional view illustrating another upper housing structure according to an embodiment of the present invention, which can be reversibly attached to a lower housing structure;

[0020] Figure 9 This is a sectional view illustrating a reversible connection between an upper housing structure and a lower housing structure according to another embodiment of the invention, for forming a central air passage and side air passages to allow air to circulate therebetween;

[0021] Figure 10This is an example Figure 9 A cross-sectional view of an alternative arrangement of the microfluidic device and heating element in the upper housing structure shown; and

[0022] Figure 11 Another cooling device for cooling a microfluidic device according to an embodiment of the present invention is illustrated;

[0023] For the purpose of clarity and brevity, the same elements and parts will have the same names and numbers in all the accompanying drawings, which are not necessarily drawn to scale. Detailed Implementation

[0024] In the foregoing overview, detailed description, appended claims, and drawings, reference is made to specific features of the invention (including method steps). It should be understood that the disclosure of this invention in this specification includes all possible combinations of these specific features. For example, where a specific feature is disclosed in the context of a particular aspect or embodiment of the invention or a particular claim, that feature may also be used to the extent possible in combination with and / or in the context of other specific aspects and embodiments of the invention, and generally in the present invention.

[0025] The term "at least" followed by a number is used here to indicate the beginning of a range starting with that number. This range can be a range with an upper limit or no upper limit, depending on the defined variable. For example, "at least 1" means 1 or more. The term "at most" followed by a number is used here to indicate the end of a range ending with that number. This range can be a range with 1 or 0 as its lower limit, or a range with no lower limit, depending on the defined variable. For example, "at most 4" means 4 or less, and "at most 40%" means 40% or less. In this specification, when a given range is "first number to second number" or "first number - second number," it means a range whose lower limit is the first number and whose upper limit is the second number. For example, "25 nanometers to 100 nanometers" refers to a range with a lower limit of 25 nanometers and an upper limit of 100 nanometers.

[0026] The term "acoustic imaging" is used in this paper to describe the relative difference in density / compressibility between an object and its host medium, which relates to the ability to manipulate its position using acoustic radiation pressure. An object with a higher density / compressibility than its host medium can have a positive acoustic imaging, which tends to move the object toward a pressure node. Conversely, an object with a lower density / compressibility than its host medium can have a negative acoustic imaging, which tends to move the object toward a pressure inverse node.

[0027] The term “biological entity” may be used herein to include cells, bacteria, viruses, molecules, particles including RNA and DNA, cell clusters, bacterial clusters, molecular clusters, and particle clusters.

[0028] The term "biological sample" as used herein may refer to blood, bodily fluids, tissues extracted from any part of the body, bone marrow, hair, nails, bones, teeth, liquids and solids in bodily excretions, or surface swabs from any part of the body. "Physical fluid," "fluid sample," "liquid sample," or "sample solution" may include biological samples in their original liquid form, biological entities dissolved or dispersed in a buffer solution, or biological samples dissociated from their original non-liquid form and dispersed in a buffer solution. A buffer solution is a liquid into which biological entities can be dissolved or dispersed without introducing contaminants or unwanted biological entities. Biological entities and biological samples may be obtained from humans or animals. Biological entities may also be obtained from plants and the environment, including air, water, and soil. Physical fluids or fluid samples may contain various types of magnetic or optical tags, or one or more chemical reagents that may be added in the various steps of the invention.

[0029] The term “sample flow rate” or “flow velocity” may be used herein to refer to the volume of a fluid sample that flows through a cross-section of a channel, a fluid portion, or a fluid path per unit time.

[0030] The term “relative fraction” is used in this document to refer to the ratio of a given amount of biological entities or particles to all biological entities or particles present in a fluid sample.

[0031] Now refer to Figure 1- Figure 2 The present invention describes embodiments applicable to microfluidic devices for separating particles or biological entities based on physical size and acoustic imaging. Figure 1A This is a top view of a microfluidic device 100, which includes a main channel 102; a central inlet port 104 connected to the main channel 102 at its upstream end for introducing a first input fluid into the main channel 102; side inlet ports 106 for introducing a second input fluid into the main channel 102 near two sidewalls; two side input channels 108 connected to the main channel 102 at or near its upstream end; a central outlet port 110 connected to the main channel 102 at its downstream end for extracting a first output fluid; a side outlet port 112 for extracting the second output fluid flowing near two sidewalls of the main channel 102; and two side output channels 114 connected to the main channel 102 at or near its downstream end. The microfluidic device 100 further includes one or more piezoelectric transducers 113 and 115 for generating acoustic radiation pressure for acoustic particle separation.

[0032] See also Figure 1AThe main channel 102 may have a linear shape and a nominal width W between the two sidewalls. A portion of the main channel 102 between the central inlet port 104 and the side input channel 108 may be narrower than the nominal width. Similarly, another portion of the main channel 102 between the central outlet port 110 and the side output channel 114 may be narrower than the nominal width. The widths of the side input channel 108 and the side output channel 114 may be narrower than the nominal width of the main channel 102.

[0033] Two side input channels 108 are connected to the main channel 102 at either of its two side walls, near or at its upstream end. Therefore, the second input fluid flowing through the two side input channels 108 is introduced into the main channel 102 as two streams flowing near the two side walls of the main channel 102. The first input fluid is introduced into the center of the main channel 102 and squeezed between the two streams of the second input fluid at or near the upstream end of the main channel 102.

[0034] Two side output channels 114 are connected to the main channel 102 at or near the downstream end of the main channel 102. Therefore, fluid flowing near the two side walls at or near the downstream end of the main channel 102 is diverted by the two side output channels 114 to become the second output fluid, which flows out through the side outlet port 112. The remaining fluid not diverted by the two side output channels 114 becomes the first output fluid and flows out through the central outlet port 110.

[0035] Figure 1B This is a cross-sectional view of a portion of a microfluidic device 100, showing a central inlet port 104 and a side inlet port 106 according to an embodiment of the invention. Features 102-114 of the microfluidic device 100 are recessed from the top surface 118 of a substrate 116. A substrate cap or cover 120 may be attached to the substrate 116 at the top surface 118 and cover features 102-114 of the microfluidic device 100. The substrate cap or cover 120 includes two holes or openings 122 and 124 aligned with the central inlet port 104 and the side inlet port 106, respectively. A first input fluid 126 and a second input fluid 128 may flow into the central inlet port 104 and the side inlet port 106, respectively, through the openings 122 and 124 in the substrate cap or cover 120. The substrate cap 120 may further include two additional holes or openings (not shown) aligned with the central outlet port 110 and the side outlet port 112, respectively, for extracting the first and second output fluids. The main channel 102 may have a nominal channel depth D as measured from the top surface 118.

[0036] Alternatively, such as Figure 1CAs shown in the cross-sectional view, the central inlet port 104 and the side inlet port 106 are accessible through the bottom of the microfluidic device 100. Similar to... Figure 1B In the illustrated embodiment, channels 102, 108, 114 and ports 104, 106, 110, 112 of the microfluidic device 100 are recessed from the top surface 132 of the substrate 130 into the substrate 130. Furthermore, the central inlet port 104 and the side inlet port 106 extend further to perforate the bottom surface 134 of the substrate 130 for receiving a first input fluid 126 and a second input fluid 128. The central outlet port 110 and the side outlet port 112 (… Figure 1C (Not shown) may also extend further to perforate the bottom surface 134 of the substrate 130 for discharging the first and second output fluids. A substrate cap or cover 136 may be attached to the substrate 130 at the top surface 132 of the substrate 130 and cover the channels 102, 108, 114 and ports 104, 106, 110, 112 of the microfluidic device 100.

[0037] Although Figure 1B and Figure 1C The diagram shows a first input fluid 126, which may be a buffer fluid, introduced into the central inlet port 104, and a second input fluid 128, which may contain particles or biological entities for acoustic separation, introduced into the side inlet port 106. However, depending on the operating mode of the microfluidic device 100, the first input fluid 126 and the second input fluid 128 may alternatively be introduced into the central inlet port 104 and the side inlet port 106, respectively. Furthermore, the second input fluid 128 may contain large particles or biological entities 138 and small particles or biological entities 140 for separation by acoustic radiation pressure. Alternatively, the particles or biological entities 138 and 140 may have sufficiently different acoustic profiles for acoustic separation.

[0038] See also Figures 1A-1CThe substrate 116 / 130 may comprise any suitable material, such as, but not limited to, glass, quartz, fused silica, metal, ceramic material, silicon, silicon carbide, aluminum nitride, titanium carbide, alumina, zirconium oxide, lithium niobate, magnesium oxide, or any combination thereof. Channels 102, 108, 114 and ports 104, 106, 110, 112 may be formed in the substrate 116 / 130 by removing material from the substrate 116 / 130 via any suitable method, such as, but not limited to, waterjet processing, machining, laser processing, wet etching, plasma etching, or any combination thereof. The substrate cap 120 / 136 may comprise any suitable material, such as, but not limited to, glass, quartz, fused silica, metal, polymeric material, ceramic material, silicon, silicon carbide, aluminum nitride, titanium carbide, alumina, zirconium oxide, lithium niobate, magnesium oxide, or any combination thereof. In an embodiment, the substrate 116 / 130 and the substrate cap 120 / 136 are made of the same material. The base cap 120 / 136 may be permanently or irreversibly attached to the base 116 / 130 by any suitable bonding method, such as, but not limited to, adhesive bonding, fusion bonding, anodic bonding, or any combination thereof.

[0039] The substrate 116 / 130 may alternatively comprise a moldable rubber or polymeric material, such as, but not limited to, polycarbonate or PDMS, which may be molded to form channels 102, 108, 114 and ports 104, 106, 110, 112 of the microfluidic device 100. When the substrate 116 / 130 is made of a soft or rubber-like material (such as PDMS or silicone) that lacks structural integrity and may even sag under its own weight, a substrate cap 120 / 136 made of a relatively rigid material may be used to support the substrate 116 / 130.

[0040] Figure 1D The figure shows a cross-section of a microfluidic device 100 near the upstream end of the main channel 102 according to an embodiment of the present invention. In the figures, numerals 113, 116, 120, 130 and 136-140 denote... Figures 1A-1C The component shown is the same component. See now. Figure 1D A first piezoelectric transducer 113 in the form of a lead zirconate titanate (PZT) transducer is attached to the outer or bottom surface of the substrate 116 / 130. The first piezoelectric transducer 113 may alternatively comprise any suitable piezoelectric material, such as, but not limited to, potassium niobate, sodium niobate, sodium tungstate, zinc oxide, bismuth ferrite, bismuth titanate, polyvinylidene fluoride, polyvinylidene chloride, polyimide, or any combination thereof. The first piezoelectric transducer 113 may be permanently or irreversibly attached to the bottom surface of the substrate 116 / 130 by welding or adhesives, such as, but not limited to, epoxy resin, cyanoacrylate, methacrylate, or any combination thereof.

[0041] The first piezoelectric transducer 113 can receive power in the form of an oscillating voltage with a frequency in the range of 100 kHz to 100 MHz to generate an acoustic pressure wave in the main channel 102 between the two sidewalls when liquid is present. An acoustic standing wave can form in the main channel 102 when the channel width W is an integer multiple of half the wavelength of the acoustic pressure wave, which can depend on the excitation frequency of the power applied to the first piezoelectric transducer 113 and the compressibility and density of the liquid in the main channel 102. Figure 1D The diagram shows an acoustic standing wave with half a wavelength W formed between the two sidewalls of the main channel 102, which results in a single acoustic pressure node forming at the center of the main channel 102.

[0042] The first piezoelectric transducer 113 may alternatively be attached to, by welding or adhesive, such as, but not limited to, epoxy resin, cyanoacrylate, methacrylate, or any combination thereof, as... Figure 1E The outer or top surface of the base cover 120 / 136 shown.

[0043] Figure 1F The figure shows a cross-section of a microfluidic device 100 near the downstream end of the main channel 102 according to an embodiment of the present invention. In the figures, numerals 115, 116, 120, 130, and 136-140 denote... Figures 1A-1C The same component as shown. See now. Figure 1F A second piezoelectric transducer 115, in the form of a lead zirconate titanate (PZT) transducer, is attached to the outer or bottom surface of the substrate 116 / 130. The second piezoelectric transducer 115 may alternatively comprise any suitable piezoelectric material described above for the first piezoelectric transducer 113. The second piezoelectric transducer 115 may be permanently or irreversibly attached to the bottom surface of the substrate 116 / 130 by welding or adhesive as described above.

[0044] Similar to the first piezoelectric transducer 113, the second piezoelectric transducer 115 can receive power in the form of an oscillating voltage with a frequency in the range of 100 kHz to 100 MHz to generate acoustic pressure waves in the main channel 102 between the two sidewalls when liquid is present. Figure 1F The diagram shows an acoustic standing wave with half a wavelength W formed between the two sidewalls of the main channel 102, which results in a single acoustic pressure node forming at the center of the main channel 102.

[0045] The second piezoelectric transducer 115 may alternatively be attached to, by welding or adhesive, such as, but not limited to, epoxy resin, cyanoacrylate, methacrylate, or any combination thereof, to, Figure 1G The outer or top surface of the base cover 120 / 136 shown.

[0046] The first piezoelectric transducer 113 and the second piezoelectric transducer 115 can both be attached to the bottom surface of the substrate 116 / 130 or the top surface of the substrate cover 120 / 136. Alternatively, one of the piezoelectric transducers 113 and 115 can be attached to the bottom surface of the substrate 116 / 130, while the other can be attached to the top surface of the substrate cover 120 / 136.

[0047] Figure 1D and Figure 1E Further illustrating that when the second input fluid 128 is introduced into the main channel 102 via two side input channels 108, particles or biological entities 138 and 140 from the second input fluid 128 flow along two sidewalls of the main channel 102 near its upstream end. Acoustic radiation pressure can drive larger particles or biological entities 138 towards the pressure node at the center of the main channel 102. When particles or biological entities 138 and 140 reach the downstream end of the main channel 102, as... Figure 1F and Figure 1G As shown, most of the large particles or biological entities 138 have moved to the center of the main channel 102, while most of the small particles or biological entities 140 remain close to the sidewall, thereby allowing the small particles or biological entities 140 to be diverted from the main channel 102 via the two side output channels 114.

[0048] Although Figure 1A A microfluidic device 100 is shown comprising two piezoelectric transducers 113 and 115, but any number of piezoelectric transducers may be used, each covering at least a portion of the main channel 102. For example, the two piezoelectric transducers 113 and 115 may be combined into a single piezoelectric transducer.

[0049] Although Figure 1D-Figure 1G The diagram shows a single pressure node formed in the main channel 102; however, the microfluidic device 100 of the present invention can operate with multiple pressure nodes by adjusting the nominal width of the main channel 102 and / or the excitation frequency of the power applied to the piezoelectric transducers 113 and 115. In one embodiment, all piezoelectric transducers operate at the same frequency. In another embodiment, at least one of the piezoelectric transducers operates at a different frequency than the others, resulting in a portion of the main channel 102 having a different number of pressure nodes than the other portions. For example, but not limited to, the first piezoelectric transducer 113 can operate at dual frequencies compared to the second piezoelectric transducer 115, resulting in the upstream and downstream portions of the main channel 102 each having two pressure nodes and one pressure node, respectively.

[0050] Now see Figure 2 The operation of the microfluidic device 100 under single pressure node conditions is described. In the accompanying drawings, numerals 102-114 indicate... Figure 1A The components shown are the same, and for clarity, the piezoelectric transducer is omitted. See now. Figure 2 A fluid sample containing first-type particles or biological entities 142 and second-type particles or biological entities 144 is introduced into the side inlet port 106, while buffer fluid 146 is introduced into the central inlet port 104. The first-type particles or biological entities 142 and second-type particles or biological entities 144 may have sufficiently different physical sizes and / or acoustic profiles to allow them to be separated by acoustic radiation pressure. For example, the first-type particles or biological entities 142 may have larger physical sizes and / or higher acoustic profiles, such as higher mass density and / or lower compressibility, thereby allowing acoustic radiation pressure to push the first-type particles or biological entities 142 toward a pressure node located at the center along the main channel 102.

[0051] A fluid sample containing type 1 particles or biological entities 142 and type 2 particles or biological entities 144 is introduced into the main channel 102 as two streams flowing near the sidewalls via two side inlet channels 108. The two streams of fluid sample in the main channel 102 (behaving similarly to laminar flow) are intervened by a buffer fluid 146, which acts as a sheath fluid, impeding or preventing the type 2 particles or biological entities 144 from moving towards the pressure node along the center of the main channel 102. As the fluid sample progresses downstream in the main channel 102, acoustic radiation pressure pushes the type 1 particles or biological entities 142 towards the pressure node along the center of the main channel 102, while the type 2 particles or biological entities 144 remain mostly near the sidewalls. At the downstream end of the main channel 102, the type 1 particles or biological entities 142 at the center flow out of the microfluidic device 100 through the central outlet port 110, and the type 2 particles or biological entities 144 near the sidewalls are diverted to the side outlet port 112 through the side outlet channel 114.

[0052] Figure 2 The acoustic separation process illustrated may be sensitive to the power (e.g., voltage or current) applied to the piezoelectric transducer and the flow rate of the fluid sample containing type I particles or biological entities 142 and type II particles or biological entities 144. Excessive power or insufficient flow rate may cause some of the type II particles or biological entities 144 to migrate to the central outlet port 110. Using a buffer fluid with too low a density and / or viscosity may also cause some of the type II particles or biological entities 144 to migrate to the central outlet port 110. Conversely, excessively low power or excessively high flow rate may cause some of the type I particles or biological entities 142 to be diverted to the side outlet port 112 through the side output channel 114. Using a buffer fluid with too high a density and / or viscosity may also cause some of the type I particles or biological entities 142 to be diverted to the side outlet port 112.

[0053] Figure 3Components of a cooling device 150 according to an embodiment of the present invention are illustrated. The compact cooling device 150 can be used to cool any small electronic device, particularly a microfluidic device 100 incorporating one or more piezoelectric transducers 113 and 115 that generate heat during operation. The cooling device 150 includes a thermoelectric heat pump 152 that can operate via the Peltier effect, a first heat exchanger 154, a first cooling fan 156, a second heat exchanger 158, and a second cooling fan 160. The thermoelectric heat pump 152 may have a plate shape, having a cold surface 162 and a hot surface 164 formed on opposing plate surfaces when a voltage is applied thereto via a set of wires 166, resulting in heat flowing from the cold surface 162 to the hot surface 164. The first heat exchanger 154 may include a heat-conducting plate 168 having a plurality of convection fins 170 protruding from at least one of its surfaces. Alternatively, the convection fins 170 can be replaced by convection columns or other convection structures that cool the hot air passing through them. The heat-conducting plate 168 can act as a radiator. The surface 172 of the first heat exchanger 154 opposite to the surface with fins 170 can contact the cooling surface 162 of the thermoelectric heat pump 152. Similarly, the second heat exchanger 158 may include a heat-conducting plate 174 having a plurality of convection fins 176 projecting from at least one of its surfaces. The convection fins 176 can be replaced by convection columns or other convection structures that transfer heat to the air passing through them. The heat-conducting plate 174 of the second heat exchanger 158 can act as a radiator. The surface 178 of the second heat exchanger 158 opposite to the surface with fins 176 can contact the hot surface 164 of the thermoelectric heat pump 152. The first heat exchanger 154 and the second heat exchanger 158 may each be made of a metal or alloy with good thermal conductivity, such as, but not limited to, copper, silver, aluminum, or any combination thereof. A first cooling fan 156, which may include multiple fan blades 180, may be positioned very close to the fins 170 of the first heat exchanger 154 for pushing or drawing hot air through the convection fins 170 to cool the hot air. A second cooling fan 160, which may include multiple fan blades 182, may be positioned very close to the fins 176 of the second heat exchanger 158 for pushing or drawing cold air through the hot fins 176 to cool them.

[0054] Figure 4The cooling device 150 is shown to be partially enclosed and / or attached to a lower housing structure 184, the lower housing structure 184 having a lower shell 186 surrounding a first cooling fan 156 and a first heat exchanger 154. The lower housing structure 184 has a lower central cavity 188 opening to the top of the lower housing structure 184 and located above the first cooling fan 156 to expose the first cooling fan 156 from the top of the lower housing structure 184. The lower central cavity 188 is formed adjacent to the first cooling fan 156 and opposite to the first heat exchanger 154. The lower housing structure 184 further includes two lower side cavities 190 and 192 that expose both sides of the first heat exchanger 154 to the top of the lower housing structure 184. The lower shell 186 may further partially or completely surround a thermoelectric heat pump 152. When the fan blades 180 of the first cooling fan 156 rotate, hot air can be drawn from the lower side chambers 190 and 192 through the fins 170 of the first heat exchanger 154 and discharged as cold air to the lower central chamber 188, as illustrated by airflow 194. By reversing the rotation direction of the fan blades 180, the direction of airflow 194 can be reversed, causing hot air to enter the first heat exchanger 154 through the lower central chamber 188 and flow out as cold air to the lower side chambers 190 and 192. When the fan blades 182 of the second cooling fan 160 rotate, cold air can be drawn from the side of the second heat exchanger 158 through the fins 176 of the second heat exchanger 158 and discharged as hot air to the second cooling fan 160, which is positioned very close to the fins 176 of the second heat exchanger 158, as illustrated by airflow 196. By reversing the rotation direction of the fan blades 182, the direction of the airflow 196 can be reversed, so that cold air passes through the second cooling fan 160 and impacts the fins 176 of the second heat exchanger 158, and flows out of the second heat exchanger 158 as hot air through the side of the second heat exchanger 158.

[0055] See also Figure 4 In one embodiment, the first cooling fan 156 contacts the fins 170 of the first heat exchanger 154. In another embodiment, the second cooling fan 160 contacts the fins 176 of the second heat exchanger 158. Although Figure 4 The diagram shows the first heat exchanger 154 in contact with the cold surface 162 of the thermoelectric heat pump 152, but an additional layer of heat conductors or structures may be inserted between the first heat exchanger 154 and the thermoelectric heat pump 152. Similarly, an additional layer of heat conductors or structures may be inserted between the second heat exchanger 158 and the thermoelectric heat pump 152.

[0056] Figure 5An upper housing structure 198 is shown, having an upper housing 200 that encloses a microfluidic device 202 in the form of an elongated chip and a heat-generating component 204 that can benefit from active cooling during operation. For example, but not limited to, the microfluidic device 202 may be similar to... Figures 1A-1G The microfluidic device 100 is shown. The chip-form microfluidic device 202 can be supported at both ends and can have a length of 30mm-150mm. The heating element 204 can be a vibrational source that generates or dissipates heat during operation, such as, but not limited to, a piezoelectric transducer. Alternatively, the heating element 204 can be one of any active device or component that generates heat during operation, such as, but not limited to, an optical detector, a central processing unit (CPU), a laser, an electronic controller, an actuator, and a voice coil. Although the heating element 204 is... Figure 5 While depicted as a single component, component 204 may represent several discrete components or clusters of components attached to the microfluidic device 202. The microfluidic device 202 and the heating component 204 may be replaced by any heat-generating electronics that requires active cooling during operation.

[0057] Figure 5 The upper housing structure 198 shown has an upper central cavity 206 and two upper side cavities 208 and 210. The upper central cavity 206 exposes the microfluidic device 202 and the heating element 204 to the atmosphere, while the upper side cavities 208 and 210 expose the microfluidic device 202 to the atmosphere at both ends along its length. The upper housing structure 198 may further include external electrical contacts (not shown) and wires connecting the contacts to an external power source. The wires connect the contacts to the microfluidic device 202 and / or the heating element 204. The upper housing structure 198 may further include an external port (not shown) and a fluid conduit (not shown) connecting the port to the microfluidic device 202 for introducing and extracting processed fluid samples from the same device 202.

[0058] The upper shell structure 198 can be designed to be reversibly attached to the lower shell structure 184, such as... Figure 5 and Figure 6 As shown. The upper housing structure 198 can be attached to the lower housing structure 184 via any reversible latching mechanism (not shown), such as, but not limited to, a magnetic latch or a mechanical clamp. When the two housing structures 184 and 198 are as Figure 6In the illustrated connection, the upper central cavity 206 is aligned with the lower central cavity 188 to form a central air passage between the first cooling fan 156 and the assembly of the microfluidic device 202 and the heating element 204. The two upper side cavities 208 and 210 are aligned with the two lower side cavities 190 and 192, respectively, to form two side air passages between the sides of the first heat exchanger 154 and the ends of the microfluidic device 202. The connection between the upper housing structure 198 and the lower housing structure 184 allows for a hermetically sealed connection of at least the convection fins 170 of the microfluidic device 202, the heating element 204, the first cooling fan 156, and the first heat exchanger 154. The first cooling fan 156 pushes cold air through the central air passage to the surfaces of the heating element 204 and the microfluidic device 202 to cool them by convection. The air is then heated and flows back to the first heat exchanger 154 through the side air passages, as shown in airflow 194. The heated air is cooled again by convection as it passes through the fins 170 of the first heat exchanger 154 and is circulated back to the first cooling fan 156 as cold air. Thus, the heat generated by the heating element 204 is transferred to the first heat exchanger 154 by convection with the air circulating between the central air passage and the two side air passages.

[0059] Each of the microfluidic device 202 and the heat-generating component 204 can be configured such that the largest surface area faces the incoming cold air from the first cooling fan 156 to maximize cooling efficiency. In an embodiment, the heat-generating component 204 is disposed between the microfluidic device 202 and the first cooling fan 156, thereby allowing the heat-generating component 204 to be directly cooled by the incident airflow from the first cooling fan 156.

[0060] By reversing the rotation direction of the fan blades 180 of the first cooling fan 156, the circulating airflow 194 can be reversed, causing the cold air exiting the side of the first heat exchanger 154 to flow through the side air passage formed by the upper side chambers 208, 210 and the lower side chambers 190, 192 to the assembly of the microfluidic device 202 and the heating element 204. The cold air is heated by the assembly of the microfluidic device 202 and the heating element 204 through convection, and then returns to the first cooling fan 156 through the central air passage, and then to the first heat exchanger 154, where the heated air is cooled again by convection.

[0061] After passing through the first heat exchanger 154, the cold air enclosed in the upper housing structure 198 and the lower housing structure 184 can have a lower temperature than the ambient air outside the housing structures 198 and 184 during operation. Conversely, the hot air enclosed in the upper housing structure 198 and the lower housing structure 184 can have a higher temperature than the ambient air outside the housing structures 198 and 184 during operation before entering the first heat exchanger 154.

[0062] See also Figure 6 The heat generated by the assembly of the microfluidic device 202 and the heating element 204 is transferred to the first heat exchanger 154 via convection. The thermoelectric heat pump 152 then transfers the heat from the first heat exchanger 154 to the second heat exchanger 158, where the heat is finally dissipated into the surrounding air via convection through the convection fins 176.

[0063] Once installed, the components of the microfluidic device 202 and the heating element 204 can be permanently housed within the upper housing structure 198. Therefore, when the microfluidic device 202 and the heating element 204 are changed, the removable upper housing structure 198 can be easily replaced with another. The modular approach of this invention offers several other advantages. The connection between the upper housing structure 198 and the lower housing structure 184 isolates the microfluidic device 202 and the heating element 204 from the surrounding air, which may be heated by other devices or components. Furthermore, the relatively small air volume enclosed by the housing structures 198 and 184 eliminates or minimizes condensation problems caused by humidity.

[0064] Figure 7 A detachable upper housing structure 198 is shown to accommodate the various components of the microfluidic device 202 and heating elements 203 and 205. Heating elements 203 and 205 are attached to both ends of the microfluidic device 202, which are exposed to side air channels formed by upper side chambers 208, 210 and lower side chambers 190, 192. Therefore, cold air propelled by the first cooling fan 156 exiting the side of the first heat exchanger 154 can flow through the two side air channels to the heating elements 203 and 205, as shown in the circulating airflow 195. The cold air is heated by convection by the heating elements 203 and 205 and returns to the first cooling fan 156 through the central air channel, and then to the first heat exchanger 154, where the heated air is cooled again by convection.

[0065] Each of the heating elements 203 and 205 may be a vibrational source that generates or dissipates heat during operation, such as, but not limited to, a piezoelectric transducer. Alternatively, each of the heating elements 203 and 205 may be one of any active device or component that generates heat during operation, such as, but not limited to, an optical detector, a central processing unit (CPU), a laser, an electronic controller, an actuator, and a voice coil. The microfluidic device 202 and the heating elements 203 and 205 may be replaced by any heat-generating electronic device that requires active cooling during operation.

[0066] The detachable upper housing structure 198 can be modified to accommodate different microfluidic devices and / or different heating components. For example, Figure 8Another detachable upper housing structure 212 is shown, which has an upper shell 214 in which two heating elements 216 and 218 of the microfluidic device 202 are attached at two different locations along the length of the microfluidic device 202. Similar to Figure 6 The upper housing structure 198 shown has two upper side cavities 220 and 222. When the two housing structures 212 and 184 are connected, the two upper side cavities 220 and 222 are aligned with the two lower side cavities 190 and 192 of the lower housing structure 184, respectively, to form two side air channels between the two ends of the microfluidic device 202 and the two sides of the first heat exchanger 154. The upper housing structure 212 further includes two upper central openings or cavities 224 and 226, which are aligned at one end with the two heating elements 216 and 218 and at the other end with the lower central cavity 188, thereby splitting the cold air from the first cooling fan into two streams concentrated on the two heating elements 216 and 218. Each of the heating elements 216 and 218 can be a vibrational source that generates or dissipates heat during operation, such as, but not limited to, a piezoelectric transducer. Alternatively, each of the heating elements 216 and 218 can be one of any active device or component that generates heat during operation, such as, but not limited to, an optical detector, a central processing unit (CPU), a laser, an electronic controller, an actuator, and a voice coil. The microfluidic device 202 and the heating elements 216 and 218 can be replaced by any heat-generating electronics that require active cooling during operation.

[0067] During operation, the first cooling fan 156 pushes cold air through the lower central cavity 188 and the two upper central cavities 224 and 226 to the surfaces of the heating elements 216 and 218 and the microfluidic device 202, thereby cooling the elements 216 and 218 and the device 202 via convection. The air is then heated and flows back to the first heat exchanger 154 through two side air channels, as shown in airflow 194. The heated air is further cooled by convection as it passes through the fins 170 of the first heat exchanger 154 and is circulated back to the first cooling fan 156 as cold air. Each of the microfluidic device 202 and the heating elements 216 and 218 can be configured such that the largest surface area faces the incoming cold air from the first cooling fan 156 to maximize cooling efficiency. In an embodiment, the heating elements 216 and 218 are disposed between the microfluidic device 202 and the first cooling fan 156, thereby allowing the heating elements 216 and 218 to be directly cooled by the incident airflow from the first cooling fan 156.

[0068] Figure 9This is a cross-sectional view illustrating an upper housing structure 228 according to another embodiment of the invention, which can be reversibly attached to a lower housing structure 230. A cooling device 150 can be partially enclosed and / or attached to the lower housing structure 230, which has a lower shell 232 surrounding a first cooling fan 156 and a first heat exchanger 154. The lower housing structure 230 has a lower central cavity 234 formed adjacent to and opposite the first cooling fan 156 and the first heat exchanger 154, and opens to the top of the lower housing structure 230, thereby exposing the first cooling fan 156 from the top of the lower housing structure 230. The lower housing structure 230 further includes a lower side cavity 236 formed adjacent to the side of the first heat exchanger 154. The lower side cavity 236 opens to the top of the lower housing structure 230, thus exposing the side of the first heat exchanger 154 from the top of the lower housing structure 230. The lower housing 232 may further partially or completely enclose the thermoelectric heat pump 152. When the fan blades 180 of the first cooling fan 156 rotate, hot air can be drawn from the lower side cavity 236 through the fins 170 of the first heat exchanger 154 and discharged as cold air to the lower central cavity 234, as illustrated by airflow 238.

[0069] See also Figure 9 The upper housing structure 228 has an upper housing 240 that encloses a microfluidic device 202 in the form of an elongated chip and a heat-generating component 204 that can benefit from active cooling during operation. For example, but not limited to, the microfluidic device 202 may be similar to Figures 1A-1G The microfluidic device 100 is shown. The chip-form microfluidic device 202 can be supported at both ends and can have a length of 30 mm to 150 mm. The heating element 204 can be a vibrational source that generates or dissipates heat during operation, such as, but not limited to, a piezoelectric transducer. Alternatively, the heating element 204 can be one of any active device or component that generates heat during operation, such as, but not limited to, an optical detector, a central processing unit (CPU), a laser, an electronic controller, an actuator, and a voice coil. The microfluidic device 202 and the heating element 204 can be replaced by any heat-generating electronic device that can benefit from active cooling during operation.

[0070] The upper housing structure 228 has an upper central cavity 242, which may be formed adjacent to the heating element 204 and open to the bottom of the upper housing structure 228, thereby exposing the microfluidic device 202 and the heating element 204 from the bottom of the upper housing structure 228. The upper housing structure 228 further includes an upper side cavity 244, which exposes one end of the microfluidic device 202 to the bottom of the upper housing structure 228 along the length of the microfluidic device 202. The upper housing structure 228 may further include an electrical contact (not shown) and a wire, the electrical contact being external for connection to an external power source, the wire connecting the electrical contact to the microfluidic device 202 and / or the heating element 204. The upper housing structure 228 may further include an external port (not shown) and a fluid tube (not shown) connecting the port to the microfluidic device 202 for introducing a fluid sample into the microfluidic device 202 and extracting a processed fluid sample from the same device 202.

[0071] The upper housing structure 228 can be designed to be reversibly attached to the lower housing structure 230. The upper housing structure 228 can be attached to the lower housing structure 230 via any reversible latching mechanism, such as, but not limited to, a magnetic latch or a mechanical clamp. When the two housing structures 228 and 230 are as follows... Figure 9 In the illustrated connection, the upper central cavity 242 is aligned with the lower central cavity 234 to form a central air passage between the first cooling fan 156 and the assembly of the microfluidic device 202 and the heating element 204, and the upper side cavity 244 is aligned with the lower side cavity 236 to form a side air passage between one side of the first heat exchanger 154 and one end of the microfluidic device 202. The connection of the upper housing structure 228 and the lower housing structure 230 allows for a hermetically sealed connection of at least the convection fins 170 of the microfluidic device 202, the heating element 204, the first cooling fan 156, and the first heat exchanger 154. The first cooling fan 156 pushes cold air through the central air passage to the surfaces of the heating element 204 and the microfluidic device 202 to cool them via convection, after which the air is heated and flows back to the first heat exchanger 154 through the side air passage, as shown in airflow 238. The heated air is cooled again by convection as it passes through the fins 170 of the first heat exchanger 154 and is circulated back to the first cooling fan 156 as cold air. Thus, the heat generated by the heat-generating component 204 is transferred to the first heat exchanger 154 by convection with the air circulating between the central air passage and the side air passage.

[0072] Figure 10 This illustrates that in the upper housing structure 228, the heating element 205 can be attached to one end of the microfluidic device 202. In this arrangement, Figure 9The airflow 238 shown can be reversed, so that the cold air driven by the first cooling fan 156 exiting the first heat exchanger 154 can flow through the side air passage formed by the upper side cavity 236 and the lower side cavity 244 to the heating element 205, as shown in the circulating airflow 246. The cold air is heated by the heating element 205 via convection and returns to the first cooling fan 156 through the central air passage, and then to the first heat exchanger 154, where the heated air is cooled again by convection.

[0073] Figures 3-10 The cooling device 150 shown may further include a heat conductor or structure in an additional layer between the second heat exchanger 158 and the thermoelectric heat pump 152. Figure 11 A cooling device 248 is shown attached to the lower housing structure 184. The cooling device 248 and... Figures 3-10 The difference in the cooling device 150 is that the heat-conducting plate 250 contacts the hot surface 164 of the thermoelectric heat pump 152, and a conductive pipe 252 is disposed between the heat-conducting plate 250 and the heat-conducting plate 174 of the second heat exchanger 158. One section of the conductive pipe 252 may contact the heat-conducting plate 250, while another section of the pipe 252 may contact the heat-conducting plate 174. The conductive pipe 252 may contain a circulating fluid to transfer heat between the heat-conducting plate 250 and the second heat exchanger 158.

[0074] While the invention has been shown and described with reference to certain preferred embodiments, it should be understood that those skilled in the art will undoubtedly contemplate certain changes and modifications thereto, which still encompass the true spirit and scope of the invention. For example, the microfluidic device and the heating element attached thereto can be replaced by other small electronic devices that require active cooling during operation. Therefore, the scope of the invention should be determined by the appended claims and their legal equivalents, rather than by the given examples.

Claims

1. A microfluidic system for separating biological entities, comprising: The cooling device includes a thermoelectric heat pump, a first fan, and a first heat exchanger disposed between the first fan and the thermoelectric heat pump; A first housing structure has a first housing surrounding the first fan and the first heat exchanger, and the first housing structure has a first cavity and a second cavity respectively exposing the two sides of the first heat exchanger, and a third cavity formed adjacent to the first fan and opposite to the first heat exchanger. A microfluidic device and one or more piezoelectric transducers attached to the microfluidic device; as well as A second housing structure, reversibly attached to the first housing structure and having a second shell therein, encloses the microfluidic device and the one or more piezoelectric transducers. The second housing structure includes a fourth cavity, a fifth cavity, and a sixth cavity, the fourth and fifth cavities respectively exposing both ends of the microfluidic device. When the first housing structure and the second housing structure are connected, the first cavity and the second cavity are aligned with the fourth cavity and the fifth cavity respectively to form a first air passage and a second air passage between the two sides of the first heat exchanger and the two ends of the microfluidic device. The third cavity and the sixth cavity are aligned to form a third air passage between the first fan and the one or more piezoelectric transducers, thereby allowing air to circulate between the third air passage and the first air passage and the second air passage.

2. The microfluidic system of claim 1, wherein the first heat exchanger comprises a plurality of convection fins protruding from a plate of a heat conductor.

3. The microfluidic system of claim 1, wherein when the first housing structure and the second housing structure are connected, the microfluidic device and the one or more piezoelectric transducers attached to the microfluidic device are hermetically sealed.

4. The microfluidic system of claim 1, wherein the microfluidic device is in the form of an elongated chip and is supported at both ends in the second housing structure.

5. The microfluidic system of claim 1, wherein the one or more piezoelectric transducers are directly cooled by incident air from the first fan.

6. The microfluidic system of claim 1, wherein the heat generated by the one or more piezoelectric transducers is transferred to the first heat exchanger via convection of air circulating between the third air channel and the first and second air channels.

7. The microfluidic system of claim 1, wherein the microfluidic device comprises a substrate in which grooves are formed and a cap covering the grooves, the one or more piezoelectric transducers being attached to the cap opposite to the substrate.

8. The microfluidic system of claim 1, wherein the thermoelectric heat pump is a Peltier device.

9. The microfluidic system of claim 1, wherein the cooling device further comprises a second fan and a second heat exchanger disposed between the second fan and the thermoelectric heat pump.

10. The microfluidic system of claim 9, wherein the thermoelectric heat pump transfers heat from the first heat exchanger to the second heat exchanger.

11. A microfluidic system for separating biological entities, comprising: The cooling device includes a thermoelectric heat pump, a first fan, and a first heat exchanger disposed between the first fan and the thermoelectric heat pump; A first housing structure having a first housing surrounding the first fan and the first heat exchanger, the first housing structure having a first cavity exposing the side of the first heat exchanger and a second cavity formed adjacent to the first fan and opposite to the first heat exchanger; A microfluidic device and one or more piezoelectric transducers attached to the microfluidic device; as well as A second housing structure is reversibly attached to the first housing structure and has a second housing, wherein the second housing encloses the microfluidic device and the one or more piezoelectric transducers, and the second housing structure includes a third cavity and a fourth cavity, the third cavity exposing the end of the microfluidic device; When the first housing structure and the second housing structure are connected, the first cavity and the third cavity are aligned to form a first air passage between the side of the first heat exchanger and the end of the microfluidic device, and the second cavity and the fourth cavity are aligned to form a second air passage between the first fan and the one or more piezoelectric transducers, thereby allowing air to circulate between the first air passage and the second air passage.

12. The microfluidic system of claim 11, wherein the first heat exchanger comprises a plurality of convection fins protruding from a plate of a heat conductor.

13. The microfluidic system of claim 11, wherein when the first housing structure and the second housing structure are connected, the microfluidic device and the one or more piezoelectric transducers attached to the microfluidic device are hermetically sealed.

14. The microfluidic system of claim 11, wherein the microfluidic device is in the form of an elongated chip and is supported at both ends in the second housing structure.

15. The microfluidic system of claim 11, wherein the one or more piezoelectric transducers are directly cooled by incident air from the first fan.

16. The microfluidic system of claim 11, wherein the heat generated by the one or more piezoelectric transducers is transferred to the first heat exchanger by convection of air circulating between the first air channel and the second air channel.

17. The microfluidic system of claim 11, wherein the microfluidic device includes a substrate in which grooves are formed and a cap covering the grooves, the one or more piezoelectric transducers being attached to the cap opposite to the substrate.

18. The microfluidic system of claim 11, wherein the thermoelectric heat pump is a Peltier device.

19. The microfluidic system of claim 11, wherein the cooling device further comprises a second fan and a second heat exchanger disposed between the second fan and the thermoelectric heat pump.

20. The microfluidic system of claim 19, wherein the thermoelectric heat pump transfers heat from the first heat exchanger to the second heat exchanger.

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