A microfluidic device that uses dielectrophoresis to concentrate target particles in a fluid sample

Abstract

A microfluidic device is disclosed that utilizes dielectrophoresis (DEP) to concentrate target particles in a fluid sample. The microfluidic device includes an inlet chamber with a fluid inlet for receiving a fluid sample, an outlet chamber with a fluid outlet for discharging the fluid sample, and a plurality of DEP channels. Each of the plurality of DEP channels is fluidly connected to the inlet chamber and the outlet chamber. As a result, a flow path from the fluid inlet to the fluid outlet is provided through each of the plurality of DEP channels. The microfluidic device is configured such that each of the flow paths has substantially the same fluid resistance.

Description

[Technical Field]

[0001] The present invention relates to a microfluidic device and related methods for concentrating target particles in a fluid sample using dielectrophoresis (DEP). [Background technology]

[0002] Microfluidic systems can be used to provide rapid point-of-care diagnosis of health conditions, such as infection by pathogens, from bodily fluid samples provided by patients.

[0003] Microfluidic systems for point-of-care testing typically include a microfluidic diagnostic device and a microfluidic cassette. A fluid sample from a patient is introduced into the microfluidic cassette, which is then inserted into a microfluidic diagnostic device for processing. The microfluidic diagnostic device typically includes processing and detection components, such as heaters, actuators, and image sensors, that interact with the microfluidic cassette during testing. The microfluidic cassette typically contains multiple microfluidic channels through which the fluid sample passes and interacts with various reagents contained within the microfluidic cassette in a process controlled from outside the cassette by the microfluidic diagnostic device.

[0004] A challenge that arises with microfluidic diagnostic systems is that it can be difficult to identify the presence of target particles, such as pathogens, in a fluid sample if only small amounts of the target particle are present. This can be particularly problematic when tests need to be performed quickly, such as in point-of-care settings, because large volumes of fluid sample must be processed to identify enough target particles to return a positive result. Processing large volumes of fluid sample can increase the time required to perform the test.

[0005] To improve detection of target particles in a fluid sample, it is known to use DEP technology in microfluidic devices to concentrate target particles in the fluid sample. DEP is a process that exerts a force on dielectric particles by exposing them to a spatially non-uniform electric field. The movement of dielectric particles can be induced via DEP toward an electrode (positive DEP) or DEP away from an electrode (negative DEP).

[0006] Patent Document 1 discloses a microfluidic device that uses DEP technology to concentrate pathogens in a fluid sample. The device includes an array of parallel-arranged DEP channels, each associated with one or more DEP electrodes. The fluid sample passes simultaneously through the array of DEP channels. The DEP electrodes selectively capture pathogens present in the fluid sample against the walls of the DEP channels as the fluid sample passes through the DEP channels.

[0007] Processing fluid samples using an array of DEP channels arranged in parallel, rather than using a single DEP channel, is advantageous because the flow rate through each DEP channel can be reduced without reducing the overall flow rate through the device, allowing fluid samples to be processed at higher volumetric flow rates while maintaining desirable fluid flow characteristics (e.g., laminar rather than turbulent flow). [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2017 / 220534 Summary of the Invention [Problem to be solved by the invention]

[0009] The device disclosed in U.S. Patent No. 6,277,999 uses a series of branching inlet and outlet channels to direct a fluid sample through parallel DEP channels. While useful for directing a fluid sample through multiple parallel DEP channels, branching inlet and outlet channels occupy a large amount of surface area on the device and may require channels to be provided at different depths within the device. This can be disadvantageous because it increases the size and cost of the device and the complexity of its manufacture. Providing a compact, low-cost, and easy-to-manufacture device is particularly important when the device is used at the point of care.

[0010] Additionally, the branched inlet and outlet channels closest to the DEP channel have small cross-sectional areas. This can make fabricating the channels more difficult and costly. Furthermore, the use of branched inlet and outlet channels exposes the fluid sample passing through the device to a larger surface area of ​​the channel walls. This, combined with the low cross-sectional area of ​​the branched inlet and outlet channels, can increase the adsorption of target particles present in the fluid sample to the channel walls, thereby reducing the sensitivity of tests performed on the fluid sample. [Means for solving the problem]

[0011] According to a first aspect of the present invention, there is provided a microfluidic device for concentrating target particles in a fluid sample using dielectrophoresis (DEP). The microfluidic device comprises an inlet chamber including a fluid inlet for receiving the fluid sample, an outlet chamber including a fluid outlet for discharging the fluid sample, and a plurality of DEP channels. Each DEP channel is fluidically connected to the inlet and outlet chambers such that a fluid path from the fluid inlet to the fluid outlet is provided through each DEP channel, and the microfluidic device is configured such that each fluid path has substantially the same fluidic resistance.

[0012] Optionally, a plurality of DEP flow paths are fluidly connected to the inlet chamber at spaced apart locations along the elongated portion of the inlet chamber and fluidly connected to the outlet chamber at spaced apart locations along the elongated portion of the outlet chamber.

[0013] Optionally, the elongated portion of the inlet chamber and the elongated portion of the outlet chamber constitute elongated walls of the inlet chamber and the outlet chamber, respectively.

[0014] Optionally, the fluid inlet is positioned along the elongated portion of the inlet chamber before the first DEP channel of the plurality of DEP channels.

[0015] Optionally, the fluid inlet is located at an end of the inlet chamber.

[0016] Optionally, the fluid outlet is positioned along the elongated portion of the outlet chamber after the last DEP channel of the plurality of DEP channels.

[0017] Optionally, the fluid outlet is located at an end of the outlet chamber.

[0018] Optionally, the inlet chamber is shaped such that fluid resistance increases from the fluid inlet along the narrow portion of the inlet chamber, and the outlet chamber is shaped such that fluid resistance decreases along the narrow portion of the outlet chamber towards the fluid outlet.

[0019] Optionally, the inlet chamber is shaped such that a cross-sectional area of ​​the inlet chamber decreases from the fluid inlet along the narrow portion of the inlet chamber, and the outlet chamber is shaped such that a cross-sectional area of ​​the outlet chamber increases toward the fluid outlet along the narrow portion of the outlet chamber.

[0020] Optionally, the fluid resistance increases from the fluid inlet along the narrowed portion of the inlet chamber by an amount corresponding to the fluid resistance decreasing along the narrowed portion of the outlet chamber towards the fluid outlet.

[0021] Optionally, the outer wall of the inlet chamber and / or the outer wall of the outlet chamber has a continuously curved shape along at least part of its length.

[0022] Optionally, the outer wall forms part of the fluid inlet or fluid outlet.

[0023] Optionally, each of the fluid paths has substantially the same length.

[0024] Optionally, each DEP flow path of the plurality of DEP flow paths has substantially the same fluid resistance.

[0025] Optionally, the microfluidic device is a microfluidic cassette.

[0026] Optionally, the fluid inlet is connected to a first microfluidic channel of the microfluidic device and the fluid outlet is connected to a further microfluidic channel of the microfluidic device such that the fluid sample can pass from the first microfluidic channel to the further microfluidic channel.

[0027] Optionally, each of the plurality of DEP channels comprises a microfluidic channel associated with one or more DEP electrodes, the one or more DEP electrodes positioned to selectively capture target particles flowing through the microfluidic channel.

[0028] According to a second aspect of the present invention, there is provided a method for concentrating target particles in a fluid sample on a microfluidic device using dielectrophoresis (DEP), the method comprising flowing the fluid sample through a plurality of fluid paths from a fluid inlet at an inlet chamber to a fluid outlet at an outlet chamber through a plurality of DEP channels fluidly connected to the inlet and outlet chambers, the microfluidic device being configured such that each fluid path has substantially the same fluidic resistance.

[0029] Advantageously, in contrast to existing microfluidic devices that use a series of branching inlet and outlet channels to direct a fluid sample through multiple DEP channels, microfluidic devices configured in accordance with embodiments of the present invention can avoid the need for branching channels by fluidly connecting each DEP channel to an inlet chamber and an outlet chamber. The inlet chamber and outlet chamber each define an enclosed space within the microfluidic device. The inlet chamber directs the fluid sample from the fluid inlet of the inlet chamber to the inlet of each DEP channel, and the outlet chamber directs the fluid sample from the outlet of each DEP channel to the fluid outlet of the outlet chamber.

[0030] In this manner, the DEP channels are connected in parallel across a common inlet and outlet chamber. Multiple fluid paths between the fluid inlets and fluid outlets are provided through the respective DEP channels. The device is configured such that each of the multiple fluid paths has substantially the same fluid resistance.

[0031] Advantageously, the multiple fluid paths have substantially the same fluid resistance, such that, in use, the fluid sample flows through each of the multiple DEP channels at substantially the same volumetric flow rate. Furthermore, using multiple DEP flow paths in parallel can reduce the flow rate of the fluid sample through each DEP channel. Advantageously, this can improve the fluid flow characteristics through the DEP channels by ensuring regular laminar flow through each DEP channel and preventing bubble formation. Improving the fluid flow characteristics through the DEP channels can, in turn, improve the ability of the DEP electrodes to capture target particles.

[0032] Furthermore, the described advantageous fluid flow characteristics can be provided in a manner that occupies significantly less surface area and is simpler to fabricate than existing arrangements, such as those that use a series of branched inlet and outlet channels. Occupying a smaller "footprint" can be particularly advantageous when the microfluidic device is used as part of a microfluidic cassette for point-of-care use, as the microfluidic cassette can be more compact and less complex and expensive to fabricate.

[0033] Advantageously, microfluidic devices configured in accordance with embodiments of the present invention may be easier and cheaper to manufacture than existing microfluidic devices because they do not need to include a series of narrow branching inlet and outlet channels to simultaneously deliver a fluid sample to multiple DEP channels.

[0034] Advantageously, a fluid sample passing through a microfluidic device configured in accordance with embodiments of the present invention is exposed to a small surface area of ​​the channel / chamber walls, which can improve the sensitivity of tests performed on the fluid sample by reducing the amount of target particles present in the fluid sample that adsorb to the channel / chamber walls.

[0035] Various further features and aspects of the present invention are defined in the claims. [Brief explanation of the drawings]

[0036] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which like parts have corresponding reference numerals and in which: [Figure 1] FIG. 1 is a simplified schematic diagram of a microfluidic device according to certain embodiments of the present invention. [Figure 2] FIG. 1 is a simplified schematic diagram of a further microfluidic device according to certain embodiments of the present invention. [Figure 3] FIG. 3 is a simplified schematic diagram of the microfluidic device of FIG. 2 including multiple DEP electrodes, according to certain embodiments of the present invention. [Figure 4] 1 is a simplified schematic diagram of a further microfluidic device, in accordance with certain embodiments of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0037] FIG. 1 is a simplified schematic diagram of a microfluidic device 100 in accordance with certain embodiments of the present invention. Microfluidic device 100 is operable to concentrate target particles, such as pathogens, in a fluid sample using dielectrophoresis (DEP). Microfluidic device 100 may be part of a microfluidic cassette arranged to be inserted into a microfluidic diagnostic device for processing of a fluid sample present in the microfluidic cassette. It will be understood that microfluidic device 100 will typically include additional components necessary for processing of the fluid sample in addition to those shown in FIG. 1 .

[0038] The microfluidic device 100 comprises an inlet chamber 101 and an outlet chamber 102. The microfluidic device 100 further comprises a first DEP channel 105a, a second DEP channel 105b, and a third DEP channel 105c fluidly connected to the inlet chamber 101 and the outlet chamber 102.

[0039] The inlet chamber 101 includes a fluid inlet 103, and the outlet chamber 102 includes a fluid outlet 104. The fluid inlet 103 is located in an end wall of the inlet chamber 101, and the fluid outlet 104 is located in an end wall of the outlet chamber 102.

[0040] The inlet chamber 101 and the outlet chamber 102 each define an enclosed space within the microfluidic device 100 .

[0041] The inlet chamber 101 is an elongated chamber. The inlet chamber 101 is configured such that fluid resistance increases from the fluid inlet 103 along the elongated portion of the inlet chamber 101, to which the multiple DEP channels are connected. The elongated portion of the inlet chamber 101 extends between a first end of the inlet chamber 101 adjacent to the fluid inlet 103 and a second end of the inlet chamber 101 remote from the fluid inlet 103. The fluid resistance increases along the elongated portion of the inlet chamber 101 because the first end of the inlet chamber 101 adjacent to the fluid inlet 103 has a larger cross-sectional area than the second end of the inlet chamber 101.

[0042] Fluid resistance will be understood to mean the resistance to the flow of a fluid through an area (also known as hydraulic impedance).

[0043] The outlet chamber 102 substantially corresponds to the inlet chamber 101. The outlet chamber 102 is shaped such that fluid resistance decreases along a narrow portion of the outlet chamber 102, to which the plurality of DEP channels are connected, toward the fluid outlet 104. The narrow portion of the outlet chamber 102 extends between a first end of the outlet chamber 102 adjacent to the fluid outlet 104 and a second end of the outlet chamber 102 remote from the fluid outlet 104. The fluid resistance decreases along the narrow portion toward the fluid outlet 104 by virtue of the first end of the outlet chamber 102 adjacent to the fluid outlet 104 having a larger cross-sectional area than the second end of the outlet chamber 102.

[0044] Typically, the shapes of the inlet chamber 101 and the outlet chamber 102 correspond substantially such that the fluid resistance increases from the fluid inlet 103 along the elongated portion of the inlet chamber 101 by an amount that corresponds to the decrease along the elongated portion of the outlet chamber 102 toward the fluid outlet 104. As shown in Figure 1, the outlet chamber 102 has a shape that corresponds to the inlet chamber 101, but is rotated 180 degrees relative to the inlet chamber 101 so that the fluid inlet 103 and the fluid outlet 104 are on opposite sides of the microfluidic device 100.

[0045] The fluid inlet 103 is positioned to receive a fluid sample such that the fluid sample is introduced into the inlet chamber 101 , and the fluid outlet 104 is positioned to allow the fluid sample to be discharged from the outlet chamber 102 .

[0046] Fluid inlet 103 may be connected to a microfluidic channel of microfluidic device 100, and fluid outlet 104 may be connected to a further microfluidic channel of microfluidic device 100. In use, as described in more detail below, fluid inlet 103 and fluid outlet 104 are used to pass a fluid sample into and out of the portion of microfluidic device 100 shown in FIG.

[0047] First DEP channel 105 a , second DEP channel 105 b , and third DEP channel 105 c are microfluidic channels associated with one or more DEP electrodes (not shown) of microfluidic device 100 .

[0048] First DEP channel 105 a, second DEP channel 105 b, and third DEP channel 105 c are arranged to perform DEP on a fluid sample passing through these channels, and DEP electrodes can be selectively activated as the fluid sample passes through the multiple DEP channels so that target particles, such as pathogens, can be selectively captured on the surfaces of the DEP channels associated with the DEP electrodes.

[0049] Each of the first DEP flow path 105a, the second DEP flow path 105b, and the third DEP flow path 105c is fluidly connected at a first end to the inlet chamber 101 and at a second end to the outlet chamber 102 such that fluid can pass from the inlet chamber 101 to the outlet chamber 102 through each of the plurality of DEP flow paths 105a, 105b, and 105c. The plurality of DEP channels are fluidly connected to the inlet chamber 101 at spaced apart locations along the elongated portion of the inlet chamber 101 provided by the elongated wall of the inlet chamber 101. Similarly, the DEP flow paths are in fluid communication with the outlet chamber 102 at spaced apart locations along the elongated portion of the outlet chamber 102 provided by the elongated wall of the outlet chamber 102.

[0050] The multiple DEP channels are fluidly connected to the inlet chamber 101 in sequence such that the first DEP channel 105a is positioned adjacent to the fluid inlet 103, the second DEP channel 105b is positioned adjacent to the first DEP channel 105a, and the third and final DEP channel 105c is adjacent to the second DEP channel 105b and is positioned furthest from the fluid inlet 103.

[0051] The DEP channels are fluidly connected to the outlet chamber 102 in the reverse order of the order in which the DEP channels are fluidly connected to the fluid inlets and outlets in the inlet chamber 101. The third DEP flow path 105c is located adjacent to the fluid outlet 104, the second DEP flow path 105b is located adjacent to the third DEP flow path 105c, and the first DEP flow path 105a is located adjacent to the second DEP flow path 105b and is furthest from the fluid outlet 104.

[0052] Each of the first DEP flow path 105a, the second DEP flow path 105b, and the third DEP flow path 105c is fluidly connected at a first end to the inlet chamber 101 and at a second end to the outlet chamber 102 such that fluid can pass from the inlet chamber 101 to the outlet chamber 102 through each of the plurality of DEP flow paths 105a, 105b, and 105c. The plurality of DEP channels are fluidly connected to the inlet chamber 101 at spaced apart locations along the elongated portion of the inlet chamber 101 provided by the elongated wall of the inlet chamber 101. Similarly, the DEP flow paths are in fluid communication with the outlet chamber 102 at spaced apart locations along the elongated portion of the outlet chamber 102 provided by the elongated wall of the outlet chamber 102.

[0053] The multiple DEP channels are fluidly connected to the inlet chamber 101 in sequence such that the first DEP channel 105a is positioned adjacent to the fluid inlet 103, the second DEP channel 105b is positioned adjacent to the first DEP channel 105a, and the third and final DEP channel 105c is adjacent to the second DEP channel 105b and is positioned furthest from the fluid inlet 103.

[0054] The DEP channels are fluidly connected to the outlet chamber 102 in the reverse order of the order in which the DEP channels are fluidly connected to the fluid inlets and outlets in the inlet chamber 101. The third DEP flow path 105c is located adjacent to the fluid outlet 104, the second DEP flow path 105b is located adjacent to the third DEP flow path 105c, and the first DEP flow path 105a is located adjacent to the second DEP flow path 105b and is furthest from the fluid outlet 104.

[0055] In this manner, the DEP channel connected to inlet chamber 101 at a location closest to fluid inlet 103 is connected to outlet chamber 102 at a location farthest from fluid outlet 104. Similarly, the DEP channel connected to inlet chamber 101 at a location farthest from fluid inlet 103 is connected to outlet chamber 102 at a location closest to fluid outlet 104.

[0056] FIG. 1 also shows multiple fluid paths for fluid to flow between fluid inlet 103 and fluid outlet 104 .

[0057] A first pathway 106 a is shown from the fluid inlet 103 through the inlet chamber 101 , through the first DEP channel 105 a , through the outlet chamber 102 to the fluid outlet 104 .

[0058] A second pathway 106 b is shown from the fluid inlet 103 through the inlet chamber 101 , through the second DEP channel 105 b , through the outlet chamber 102 to the fluid outlet 104 .

[0059] The third pathway 106c shows a pathway from the fluid inlet 103 through the inlet chamber 101, through the third DEP channel 105c, through the outlet chamber 102 and to the fluid outlet 104.

[0060] The microfluidic device 100 is arranged so that the fluidic resistance experienced by a fluid sample passing along each path 106a 106b 106c through the microfluidic device 100 is substantially the same depending on the shape and configuration of the inlet chamber 101 and the outlet chamber 102 and the order in which the multiple DEP channels are fluidly connected to the inlet chamber 101 and the outlet chamber 102.

[0061] For example, a fluid sample passing along first pathway 106a experiences a relatively small amount of fluidic resistance within inlet chamber 101 due to the short distance from fluid inlet 103 to the inlet of first DEP channel 105a and the large cross-sectional area of ​​the portion of inlet chamber 101 through which the fluid sample passes. As the fluid travels along first pathway 106a, the fluid sample experiences a relatively large amount of fluidic resistance from the outlet of first DEP channel 105a, through outlet chamber 102, to fluid outlet 104 due to the long distance from the outlet of first DEP channel 105a to fluid outlet 104 and the small cross-sectional area of ​​the portion of outlet chamber 102 through which the fluid sample passes.

[0062] In contrast, a fluid sample passing along second path 106b experiences a moderate amount of fluidic resistance in inlet chamber 101 and a moderate amount of fluidic resistance in outlet chamber 102, while a fluid sample passing along third path 106c experiences a relatively large amount of fluidic resistance in inlet chamber 101 and a relatively small amount of fluidic resistance in outlet chamber 102. Microfluidic device 100 is configured to provide substantially the same fluidic resistance along each of multiple paths before and after the DEP channel. Typically, each DEP flow path has substantially the same fluidic resistance.

[0063] In this way, the microfluidic device 100 provides substantially the same fluidic resistance along each fluid path. Advantageously, this means that, in use, a fluid sample flows through each of the multiple DEP channels at substantially the same volumetric flow rate. Advantageously, this can improve fluid flow characteristics through the DEP channels by ensuring regular, laminar flow through each DEP channel and preventing bubble formation. Improving fluid flow characteristics through the DEP channels can, in turn, improve the ability of the DEP electrodes to capture target particles.

[0064] It will be appreciated that the fluid resistance along each fluid path may be determined by any suitable technique, including suitable computational fluid dynamics (CFD) techniques.

[0065] Furthermore, microfluidic device 100 can provide such beneficial fluid flow characteristics while requiring a significantly smaller surface area on microfluidic device 100 compared to existing arrangements that use a series of branching inlet and outlet channels. This can be particularly advantageous when microfluidic device 100 is part of a microfluidic cassette for use in a point-of-care environment, as the microfluidic cassette can be made more compact and cost-effective to manufacture.

[0066] Next, a method for using the microfluidic device 100 will be described.

[0067] A fluid sample containing target particles, such as pathogens, is introduced into the inlet chamber 101 via the fluid inlet 103 and passes through the microfluidic device 100 via a first path 106a, a second path 106b and a third path 106c to the fluid outlet 104.

[0068] More specifically, a fluid sample passes through inlet chamber 101 from fluid inlet 103. A portion of the fluid sample passes through each of first DEP channel 105a, second DEP channel 105b, and third DEP channel 105c. The fluid sample then passes from first DEP channel 105a, second DEP channel 105b, and third DEP channel 105c to outlet chamber 102 and is discharged from outlet chamber 102 to fluid outlet 104.

[0069] While the fluid sample passes through the multiple DEP channels, DEP electrodes associated with the multiple DEP channels are selectively activated such that target particles suspended in the fluid sample flowing through the multiple DEP channels are captured by the electrodes and adhere to the walls of the DEP channels associated with the electrodes.

[0070] The fluid sample continues to flow through the microfluidic device 100 while the target particles are captured by the DEP electrodes. The electrodes are then deactivated, re-encapsulating the target particles in the fluid sample and providing a volume of the fluid sample enriched with the target particles. This enriched fluid sample can be directed through the fluid outlet 104 for further processing.

[0071] A pump can be used to pump the fluid sample between the fluid inlet 103 and the fluid outlet 104. The pump can be part of the microfluidic device 100 or an external component.

[0072] It will be understood that in other embodiments, microfluidic device 100 may include a different number of DEP channels and corresponding paths through microfluidic device 100. Furthermore, it will be understood that the fluid paths through microfluidic device 100 are schematic and are intended to depict the general direction of fluid flow through microfluidic device 100.

[0073] The inlet chamber 101, the outlet chamber 102, the first DEP channel 105a, the second DEP channel 105b, and the third DEP channel 105c are typically formed as recessed regions in the surface of a substrate. A sealing layer is typically fixed onto the substrate to fluidically seal the microfluidic device 100.

[0074] It will be appreciated that in certain embodiments, the inlet chamber 101 and the outlet chamber 102 may take on a variety of suitable shapes and configurations to balance fluid resistance across the fluid path through the device 100 .

[0075] As explained, DEP is a process that exerts a force on a dielectric particle by exposing it to a spatially non-uniform electric field. The movement of the dielectric particle can be induced via DEP either toward an electrode (positive DEP) or away from an electrode (negative DEP).

[0076] It will be understood that the DEP electrodes disclosed herein are appropriately tailored to capture target particles using DEP when activated. For example, in some cases, a DEP electrode can use 5 MHz at 17 V (peak-to-peak) to capture M. smegmatis. However, it will be understood that a DEP electrode can operate over a range of suitable frequencies and voltages, depending on the flow rate and electrode geometry.

[0077] In certain embodiments, each of the fluid paths can have substantially the same length through the microfluidic device 100 .

[0078] Microfluidic device 100 (and other microfluidic devices described herein in accordance with embodiments of the present invention) can be used to perform a method for concentrating target particles in a fluid sample on a microfluidic device using dielectrophoresis, the method including flowing the fluid sample from a fluid inlet of an inlet chamber through multiple fluid paths through multiple DEP channels fluidly communicating with the inlet and outlet chambers to a fluid outlet of an outlet chamber, the microfluidic device configured such that each of the fluid paths has substantially the same fluidic resistance. It will be understood that the method can include additional steps and features as described herein.

[0079] FIG. 2 is a simplified schematic diagram of a further microfluidic device according to certain embodiments of the present invention.

[0080] Microfluidic device 200 substantially corresponds to microfluidic device 100 described with reference to FIG. 1, except as otherwise described and depicted.

[0081] The microfluidic device 200 comprises an inlet chamber 201 and an outlet chamber 202. The inlet chamber 201 comprises a fluid inlet 203, and the outlet chamber 202 comprises a fluid outlet 204.

[0082] Microfluidic device 200 includes first DEP channel 205a, second DEP channel 205b, third DEP channel 205c, fourth DEP channel 205d, fifth DEP channel 205e, sixth DEP channel 205f, seventh DEP channel 205g, and eighth DEP channel 205h. Each of the DEP channels has a first end fluidly connected to inlet chamber 201 and a second end fluidly connected to outlet chamber 202. Each of the DEP channels includes an inlet channel and an outlet channel on either side of a main channel.

[0083] Fluid inlet 203 is located at the end of inlet chamber 201 adjacent to first DEP channel 205a. Fluid outlet 204 is located at the end of outlet chamber 202 adjacent to eighth (and final) DEP channel 205h.

[0084] The inlet chamber 201 includes an elongated outer wall and an elongated inner wall opposite the outer wall. The DEP channels are connected along the inner wall. The inner and outer walls are substantially straight. The inner wall is angled relative to the outer wall such that the inlet chamber 201 narrows from the fluid inlet 203 along the elongated portion of the inlet chamber 201 where the DEP channels are connected.

[0085] The outlet chamber 202 has an elongated outer wall and an elongated inner wall opposite the outer wall. The DEP channels are connected along the inner wall. The inner and outer walls are substantially straight. The inner wall is angled relative to the outer wall such that the outlet chamber 202 widens toward the fluid outlet 204 along the elongated portion of the outlet chamber 202 to which the DEP channels are connected.

[0086] FIG. 3 is a simplified schematic diagram of the microfluidic device 200 of FIG. 2 including multiple DEP electrodes in accordance with certain embodiments of the present invention.

[0087] The microfluidic device 200 includes a DEP electrode array 300. The DEP electrode array 300 comprises a plurality of electrodes disposed on or immediately adjacent to a DEP channel. As described herein, the DEP electrode array 300 can be selectively activated to capture target particles suspended in a fluid sample flowing through the DEP channel. The target particles are captured in the DEP channel immediately adjacent to the DEP electrodes. The DEP electrodes can be deactivated so that the target particles are released back into the fluid flowing through the DEP channel.

[0088] FIG. 4 is a simplified schematic diagram of a microfluidic device 400 according to certain embodiments of the present invention.

[0089] The microfluidic device 400 substantially corresponds to the microfluidic device 200 described with reference to FIG. 2, except where otherwise stated and depicted.

[0090] The microfluidic device 400 comprises an inlet chamber 401 and an outlet chamber 402. The inlet chamber 401 comprises a fluid inlet 403, and the outlet chamber 402 comprises a fluid outlet 404.

[0091] The microfluidic device 400 comprises a first DEP channel 405a, a second DEP channel 405b, a third DEP channel 405c, a fourth DEP channel 405d, a fifth DEP channel 405e, a sixth DEP channel 405f, a seventh DEP channel 405g, and an eighth DEP channel 405h.

[0092] The inlet chamber 401 comprises an elongated inner wall 406 and an elongated outer wall 407. Similarly, the outlet chamber 402 comprises an elongated inner wall and an elongated outer wall.

[0093] Each of the DEP channels is in fluid communication at a first end with the inlet chamber 401 and at a second end with the outlet chamber 402, and is spaced apart along the interior walls of the inlet chamber 401 and the outlet chamber 402, respectively.

[0094] 2, the outer wall 407 of the inlet chamber 401 has a continuously curved shape, while the inner wall 406 of the inlet chamber 401 is substantially straight. At the end of the inlet chamber 401, the outer wall 407 forms part of the fluid inlet 403. The outlet chamber 402 also has a corresponding shape.

[0095] As such, the inner surfaces of the inlet chamber 401 and outlet chamber 402 exposed to the fluid sample are rounded. Advantageously, this minimizes turbulence at the inlet and outlet of each of the DEP flow paths, resulting in smoother fluid flow and improved local pressure drop characteristics across each of the DEP flow paths.

[0096] Advantageously, the geometry of the inlet chamber 401 and the outlet chamber 402 allows the DEP channels to be longer without increasing the overall size of the microfluidic device 400. Longer DEP channels are advantageous because they can improve the ability of the DEP channels to capture target particles. Furthermore, the inlet and outlet of each DEP channel have substantially the same length. This can further improve the regularity of fluid flow through each of the DEP channels.

[0097] In certain embodiments, the inlet chamber 401 has a length of approximately 20 mm along the portion of the inlet chamber 401 to which the DEP channel is connected (in this embodiment, between a first end of the inlet chamber 401 adjacent to the fluid inlet 403 and a second end of the inlet chamber 401 furthest from the fluid inlet 403).

[0098] In certain embodiments, the first end of the inlet chamber 401 adjacent the fluid inlet 403 has a width between about 2.4 mm and 2.6 mm, and the second end of the inlet chamber 401 furthest from the fluid inlet 403 has a width between about 0.4 mm and 0.5 mm. In certain embodiments, the depth of the inlet chamber 401 is about 0.06 mm.

[0099] In certain embodiments, the outlet chamber 402 has substantially the same dimensions as the inlet chamber 401 .

[0100] It will be appreciated that an array of microfluidic devices of the type disclosed herein can be used to process a fluid sample. For example, an array of four microfluidic devices of the type disclosed herein can be used to process the same fluid sample. In such an example, a portion of the fluid sample can be delivered to each device. Using more than one microfluidic device to process a fluid sample can further improve capture of target particles by further slowing the flow of fluid through the DEP channel.

[0101] It will be understood that target particles that may be captured by a microfluidic device configured in accordance with embodiments of the present invention may be pathogens (e.g., bacteria, viruses, or fungi), or other particles of interest such as proteins or cancer cells.

[0102] All features disclosed in this specification (including the accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. Each feature disclosed in this specification (including the accompanying claims, abstract, and drawings) may be replaced by an alternative feature serving the same, equivalent, or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each disclosed feature is an example of a generic series of equivalent or similar features. The invention is not limited to the details of the foregoing embodiments. The invention extends to any novel, or any novel combination of, features disclosed in this specification (including the accompanying claims, abstract, and drawings), or any novel, or any novel combination of steps of any method or process so disclosed.

[0103] With respect to the use of virtually any plural and / or singular term herein, one of ordinary skill in the art can translate from plural to singular and / or from singular to plural as appropriate to the context and / or application. Various singular / plural permutations may be expressly provided herein for clarity.

[0104] In general, those skilled in the art will understand that the terms used herein, and particularly in the appended claims, are generally intended as "open" terms (e.g., the term "comprises" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "including" should be interpreted as "including but not limited to," etc.). Those skilled in the art will further understand that if a specific number of introduced claim recitations are intended, such intention will be expressly set forth in the claim; in the absence of such recitation, no such intention exists. For example, as an aid to understanding, the following appended claims may use the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to mean that the introduction of a claim repeat with the indefinite article "a" or "an" limits a particular claim containing such introduced claim repeat to embodiments containing only one such repeat, even if the same claim may contain the introductory phrases "one or more" or "at least one" and an indefinite article such as "a" (e.g., "a" should be interpreted to mean "at least one" or "one or more"). Furthermore, even if a specific number of introduced claim repeats is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the literal recitation of "two repeats" without other modifiers means at least two repeats, or more than two repeats).

[0105] Various embodiments of the present disclosure have been described herein for purposes of illustration, and it will be understood that various changes may be made without departing from the scope of the present disclosure. Accordingly, the various embodiments disclosed herein are not intended to be limiting, with the true scope being indicated by the following claims.

Claims

1. 1. A microfluidic device for concentrating target particles in a fluid sample using dielectrophoresis (DEP), comprising: an inlet chamber having a fluid inlet for receiving a fluid sample; an outlet chamber having a fluid outlet for discharging the fluid sample; A plurality of DEP channels are provided, each of the plurality of DEP channels is fluidly connected to the inlet chamber and the outlet chamber, such that a flow path from the fluid inlet to the fluid outlet is provided through each of the plurality of DEP channels; the microfluidic device is configured such that each of the flow paths has substantially the same fluid resistance; the plurality of DEP channels are fluidly connected to the inlet chamber at spaced apart locations along the elongated portion of the inlet chamber and fluidly connected to the outlet chamber at spaced apart locations along the elongated portion of the outlet chamber; the fluid inlet is located along the elongated portion of the inlet chamber before a first DEP channel of the plurality of DEP channels; the inlet chamber is shaped such that the fluid resistance increases along the narrow portion of the inlet chamber from the fluid inlet, and the pre-exit chamber is shaped such that the fluid resistance decreases along the narrow portion of the inlet chamber towards the fluid outlet. Microfluidic devices.

2. 10. The microfluidic device of claim 1, wherein the elongated portion of the inlet chamber and the elongated portion of the outlet chamber comprise elongated walls of the inlet chamber and the outlet chamber, respectively.

3. 3. A microfluidic device according to claim 1 or 2, wherein the fluid inlet is located at an end of the inlet chamber.

4. 4. The microfluidic device of claim 2 or 3, wherein the fluid outlet is located after a final DEP channel of the plurality of DEP channels along the elongated portion of the outlet chamber.

5. 5. The microfluidic device according to claim 2, wherein the fluid outlet is located at an end of the outlet chamber.

6. 10. The microfluidic device of claim 1, wherein the inlet chamber is shaped such that a cross-sectional area of ​​the inlet chamber decreases from the fluid inlet along the elongated portion of the inlet chamber, and the outlet chamber is shaped such that a cross-sectional area of ​​the outlet chamber increases along the elongated portion of the outlet chamber toward the fluid outlet.

7. 10. A microfluidic device according to claim 1 or 6, wherein the fluidic resistance increases along the elongated portion of the inlet chamber from the fluid inlet by an amount corresponding to the fluidic resistance decreasing along the elongated portion of the outlet chamber towards the fluid outlet.

8. 8. The microfluidic device according to claim 1, wherein the outer wall of the inlet chamber and / or the outer wall of the outlet chamber has a curved shape along at least a portion of the outer wall.

9. 9. The microfluidic device of claim 8, wherein the outer wall forms part of a fluid inlet or a fluid outlet.

10. 10. The microfluidic device according to claim 1, wherein each of the channels has substantially the same length.

11. 11. The microfluidic device according to claim 1, wherein each of the plurality of DEP channels has substantially the same fluid resistance.

12. The microfluidic device according to any one of claims 1 to 11, wherein the microfluidic device is a microfluidic cassette.

13. 13. A microfluidic device according to any one of claims 1 to 12, wherein the fluid inlet is connected to a first microfluidic channel of the microfluidic device and the fluid outlet is connected to another microfluidic channel of the microfluidic device, such that a fluid sample can pass from the first microfluidic channel to the other microfluidic channel.

14. 14. A microfluidic device according to any one of claims 1 to 13, wherein each of the plurality of DEP channels comprises a microfluidic channel associated with one or more DEP electrodes, the one or more DEP electrodes being positioned to selectively capture target particles flowing through the microfluidic channel.

15. 15. A method for concentrating target particles in a fluid sample on a microfluidic device according to any one of claims 1 to 14 using dielectrophoresis (DEP), comprising flowing the fluid sample from a fluid inlet of an inlet chamber to a fluid outlet of an outlet chamber through a plurality of flow paths passing through a plurality of DEP channels fluidly connected to the inlet chamber and the outlet chamber, the microfluidic device being configured such that each of the plurality of flow paths has substantially the same fluid resistance.

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