Microfluidic device with positive displacement pump
By integrating a positive displacement pump and a fluid reservoir into a microfluidic device, the problems of contamination and leakage caused by external pump connections are solved, enabling miniaturization and cost reduction of the device, while improving the control accuracy and safety of fluid movement.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- QUANTUMDX GROUP
- Filing Date
- 2021-09-20
- Publication Date
- 2026-05-01
AI Technical Summary
The use of external pumps connected to the openings of microfluidic channels in existing microfluidic devices leads to problems such as fluid sample contamination, leakage risk, and increased device size and cost.
By employing a combination of a positive displacement pump and a fluid reservoir, and integrating the bellows pump and fluid reservoir within the microfluidic device, the fluid reservoir provides a fluid source for fluid refilling, avoiding dependence on external pumps, and the fluid flow is controlled by valves.
It reduces the size and cost of the device, prevents sample contamination and leakage, and improves the control accuracy and safety of fluid movement, making it suitable for fluid metering and DNA extraction processes.
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Figure CN116234984B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a microfluidic device and method for moving fluid samples through microfluidic channels.
[0002] background
[0003] Microfluidic devices, such as microfluidic cartridges, can be used to perform chemical and / or biochemical analysis on fluid samples provided to patients at the point of care (POC). These microfluidic devices, sometimes referred to as "lab-on-a-chip" devices, are well-known.
[0004] During operation of the microfluidic cartridge, a fluid sample moves along the cartridge's microfluidic channels through a series of "zones" where different processing steps are performed on the sample. Depending on the test performed on the sample, the processing steps may involve heating or cooling the sample, combining the sample with one or more reagents, and / or passing the sample through a filter and other treatments.
[0005] It is necessary to control the movement of fluid samples through the microfluidic cell in order to correctly perform various processing steps on the samples.
[0006] One known way to control the movement of a fluid sample through a microfluidic cell is to connect an external pump (such as a syringe, pneumatic, or peristaltic pump) to an opening on the cell that provides an inlet to the microfluidic channels. During operation, the external pump moves the sample through the cell.
[0007] However, a disadvantage of using an external pump is that the cartridge requires an opening to connect the external pump to the microfluidic channel. Having such an opening within the microfluidic channel has several drawbacks. First, it can lead to contamination of the fluid sample. This reduces the accuracy of tests performed on the sample. Furthermore, it increases the risk of leakage of the fluid sample or other potentially hazardous chemicals (such as reagents) from the cartridge. This could potentially harm the user of the device. Contamination can also occur when one cartridge comes into contact with fluid leaking from another cartridge, potentially leading to false positive results if diagnostic tests are performed on that cartridge. Additionally, external pumps and their associated control components can be large and expensive.
[0008] The purpose of certain embodiments of the present invention is to avoid or mitigate one or more of the aforementioned disadvantages. Invention Overview
[0010] According to a first aspect of the invention, a microfluidic device is provided for moving fluid through a microfluidic channel of the device. The device includes a microfluidic channel and a positive displacement pump, the positive displacement pump including a chamber fluidly connected to the microfluidic channel. The positive displacement pump is arranged such that, when the positive displacement pump is actuated, fluid in the chamber is displaced into the microfluidic channel. The device further includes a fluid reservoir fluidly connected to the chamber of the positive displacement pump to provide a fluid source for re-filling the chamber after the positive displacement pump is actuated. The fluid reservoir is arranged such that fluid within the reservoir is sealed within the device.
[0011] Optionally, the device further includes a first valve and a second valve, the first valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the microfluidic channel, and the second valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the fluid reservoir.
[0012] Optionally, at least one of the first valve and the second valve is externally actuable.
[0013] Optionally, the fluid reservoir includes a fluid storage chamber of the device.
[0014] Optionally, the fluid storage chamber is pre-pressurized to above atmospheric pressure before use.
[0015] Alternatively, the fluid storage chamber is a waste chamber arranged on the device to store waste liquid.
[0016] Optionally, the device includes a fluid loop that provides a continuous fluid flow path between the microfluidic channel and the positive displacement pump.
[0017] Optionally, the fluid storage chamber is connected to form part of a continuous fluid flow channel.
[0018] Optionally, the fluid storage chamber includes a first fluid storage chamber port and a second fluid storage chamber port, the fluid storage chamber being connected to a continuous fluid flow channel via the first fluid storage chamber port and the second fluid storage chamber port.
[0019] Optionally, the first fluid storage chamber port and the other fluid storage chamber port extend above the base surface of the fluid storage chamber, so that liquid can be stored in the fluid storage chamber below the level of the first fluid storage chamber port and the other fluid storage chamber port.
[0020] Optionally, the fluid reservoir includes an oversized portion of the microfluidic channel adjacent to the port of the positive displacement pump.
[0021] Alternatively, the positive displacement pump is a bellows pump.
[0022] Alternatively, the chamber of the bellows pump is elastically deformable.
[0023] Alternatively, the microfluidic device is a microfluidic cartridge.
[0024] According to a second aspect of the invention, a method is provided for moving fluid through a microfluidic channel of a microfluidic device. The method includes the steps of: actuating a positive displacement pump of the microfluidic device such that fluid in the chamber of the positive displacement pump is displaced into the microfluidic channel, thereby causing fluid to move through the microfluidic channel; and refilling the chamber of the positive displacement pump with a fluid source provided from a fluid reservoir of the device, said fluid reservoir being arranged such that the fluid in the reservoir is sealed within the device.
[0025] Optionally, the device further includes a first valve and a second valve, the first valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the microfluidic channel, and the second valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the fluid reservoir.
[0026] Optionally, the method further includes: closing the second valve and opening the first valve before actuating the positive displacement pump; and closing the first valve and opening the second valve before refilling the chamber.
[0027] Advantageously, according to embodiments of the invention, an efficient method is provided for moving fluid samples through a microfluidic device such as a microfluidic cell.
[0028] Advantageously, embodiments of the invention provide a microfluidic device comprising an on-board fluid reservoir that provides a fluid source for refilling (also referred to herein as "re-inflate") an on-board positive displacement pump, such as a bellows pump. The fluid reservoir is fluid-tight to prevent fluid within the reservoir from escaping from the device.
[0029] Advantageously, providing a fluid reservoir on the device means that the positive displacement pump can have a reduced volume because a single "stroke" or "compression" of the pump does not need to be able to continuously move the fluid sample through the cartridge. Instead, after being actuated, the positive displacement pump can be refilled one or more times using the fluid stored in the fluid reservoir. In this way, the pumping volume of the positive displacement pump can be smaller than the pumping volume required to move the fluid sample through the cartridge. The device may include a valve arrangement to selectively control the fluid flow through the device.
[0030] Advantageously, providing a positive displacement pump with a reduced volume can result in a smaller overall "footprint" for the unit. This has several advantages, including reduced manufacturing costs.
[0031] Advantageously, embodiments of the invention provide a fluid-sealed device. Advantageously, there is no need to provide an opening for connecting an external pump to the device. Advantageously, this helps prevent contamination of samples processed within the device. Furthermore, this prevents users of the device from coming into contact with hazardous substances within the device, such as reagents, biological fluid samples, or amplified DNA.
[0032] Advantageously, embodiments of the invention provide an apparatus comprising an on-board positive displacement pump and a fluid reservoir. That is, the positive displacement pump and the fluid reservoir are integrated into the apparatus. This reduces the overall size, cost, and complexity associated with having an external pump.
[0033] Advantageously, according to certain embodiments of the invention, a portion of the existing fluid chamber (e.g., a waste chamber) on the microfluidic device can be used as a fluid reservoir to provide a fluid source for refilling the positive displacement pump. Advantageously, this can further reduce the footprint of the microfluidic device.
[0034] Advantageously, according to certain embodiments of the invention, the fluid chamber can be connected to a positive displacement pump within a continuous fluid flow loop. This can further improve the ease with which the fluid sample can be moved through the device, because in addition to generating positive pressure behind the fluid sample, actuating the positive displacement pump also generates negative pressure in front of the fluid sample.
[0035] Advantageously, according to certain embodiments of the invention, the positive displacement pump is resilient, such that it can be mechanically biased to return to its initial pre-actuated position. Advantageously, this allows negative pressure to be generated within a portion of the microfluidic channel. Generating negative pressure in this way can be particularly useful for many applications in microfluidics, such as filtration drying in DNA extraction processes.
[0036] Advantageously, according to certain embodiments of the invention, the device can provide a precise way to control the flow of fluid through microfluidic channels, which can be used, for example, for fluid metering.
[0037] Various other features and aspects of the invention are defined in the claims. Brief description of the attached diagram
[0039] Embodiments of the invention will now be described by way of example only with reference to the accompanying drawings, in which similar parts are provided with corresponding reference numerals, and wherein:
[0040] Figure 1 This is a simplified schematic diagram of a microfluidic device according to certain embodiments of the present invention;
[0041] Figure 2 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention;
[0042] Figure 3 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention;
[0043] Figures 4A-4F This shows the usage. Figure 3 A simplified schematic diagram of a microfluidic device;
[0044] Figure 5 This is a diagram showing a cross-section of a fluid storage chamber according to certain embodiments of the present invention;
[0045] Figure 6 This is a cross-sectional view showing a valve that can be used in a microfluidic device according to certain embodiments of the present invention;
[0046] Figure 7A and Figure 7B Provided in use Figure 6 Another cross-sectional view of the valve;
[0047] Figure 8 This is a diagram illustrating a bellows pump that can be used in a microfluidic device according to certain embodiments of the present invention; and
[0048] Figure 9 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention.
[0049] Detailed description
[0050] Figure 1 This is a simplified schematic diagram of a microfluidic device according to certain embodiments of the present invention.
[0051] Microfluidic device 100 is a microfluidic cartridge (only a portion of it is shown). This cartridge is used to perform on-cassette diagnostic processing on liquid biological samples, such as blood, plasma, or urine samples obtained from human patients, and is typically used in conjunction with a benchtop or portable analyzer (“host device”), which may house components such as imaging equipment, power supply, control circuitry, and actuators. The diagnostic process may involve amplifying deoxyribonucleic acid (DNA) in the sample via polymerase chain reaction (PCR).
[0052] Throughout this document, “microfluidic” refers to at least one fluid with a size of less than 1 mm and / or capable of handling microliters or less.
[0053] The cartridge is arranged to be inserted into a host device for processing. The host device typically includes instruments that interact with the cartridge, such as mechanical actuators, heating / cooling components, and imaging components, enabling the cartridge to perform diagnostic processing on the sample. The cartridge is usually a single-use component and is disposed of after processing of the sample contained within it.
[0054] Sample processing (also referred to herein as “analysis”) is typically performed by allowing the sample to interact with reagents in one or more processing steps carried out in channels and / or chambers of apparatus 100. These processing steps are typically performed at times and temperatures that result in the formation of a detectable product, which indicates the presence or absence of an analyte in the sample.
[0055] The cartridge includes a microfluidic channel 101. The channel 101 is a closed fluid flow channel arranged to allow liquid biological samples (and / or reagents) to flow through one or more “regions” of the cartridge in which processing activities are performed on the samples.
[0056] For simplicity, Figure 1 The diagram shows a portion of a single schematic microfluidic channel. However, it should be understood that in some embodiments, the device 100 includes various additional components, including additional microfluidic channels, valves, chambers, and / or branches, etc., required for performing assays. These additional components can be used to allow mixing, washing, removal, and other actions as needed for specific assays.
[0057] It should also be understood that a range of suitable lengths and cross-sectional shapes for microfluidic channels can be used to allow for the desired delivery and handling of samples and / or reagents.
[0058] The device 100 includes a positive displacement pump. In this embodiment, the positive displacement pump is a bellows pump 102.
[0059] It should be understood that a positive displacement pump is a device arranged to move fluid by removing a certain volume of fluid from a chamber.
[0060] The bellows pump 102 includes an elastically deformable chamber. The bellows pump 102 includes a first port 103 and a second port 104. The first port 103 and the second port 104 allow fluid communication between the bellows pump 102 and other components of the device 100. In the primary operating direction of the bellows pump 102 (where a positive pressure is generated in the microfluidic channel 101 to cause fluid to move along the channel 101), the second port 104 acts as a fluid outlet through which fluid is forced out of the chamber of the bellows pump 102 and moves along the microfluidic channel 101. The first port 103 serves as a fluid inlet for refilling the chamber of the bellows pump 102 from a fluid reservoir after the bellows pump 102 has been actuated.
[0061] The bellows pump 102 is arranged to be actuated by applying mechanical force to deform the deformable chamber. While this can be done manually, it is preferable to insert a housing into a host device with an automatic actuator that cooperates with the bellows pump 102, or to apply appropriate external pressure to the outer surface of the bellows pump 102. This reduces the volume of the deformable chamber. Reducing the volume of the deformable chamber increases the pressure of the fluid (typically air) within the deformable chamber. This increase in pressure can be used to force the fluid out of the second port 104 and along the microfluidic channel 101.
[0062] Figure 8 An example of a bellows pump arrangement that can be used according to certain embodiments of the invention is shown.
[0063] The device 100 includes a first valve 105 and a second valve 106. In some embodiments, valves 105 and 106 form part of a positive displacement pump 102.
[0064] A first valve 105 is positioned adjacent to a first port 103 to selectively control fluid flow between the deformable chamber and the fluid reservoir (via the first port 103). A second valve 106 is positioned adjacent to a second port 104 to selectively control fluid flow between the deformable chamber and the microfluidic channel 101 (via the second port 104).
[0065] In some embodiments, valves 105, 106 can be externally actuated, for example by applying mechanical force to valves 105, 106 to move valves 105, 106 from an open configuration to a closed configuration.
[0066] Figure 6 and Figures 7A-7B Examples of valve mechanisms that can be used according to certain embodiments of the present invention are shown in the illustration.
[0067] The apparatus 100 includes a fluid reservoir 107. The fluid reservoir 107 stores a volume of fluid (typically air) within the apparatus 100. The fluid reservoir 107 is fluid-tight to prevent fluid within the fluid reservoir 107 from leaking out of the apparatus 100. In this way, the fluid reservoir 107 stores a volume of fluid isolated from the local ambient fluid of the apparatus 100.
[0068] Fluid reservoir 107 is connected to the first port 103 of bellows pump 102 (via first valve 105) to provide a fluid source to bellows pump 102. As described in more detail below, after bellows pump 102 has been actuated, first valve 105 can be opened, second valve 106 can be closed, and fluid from fluid reservoir 107 can be used to refill bellows pump 102 by supplying fluid to deformable chamber.
[0069] In this embodiment, fluid reservoir 107 is the fluid storage chamber of device 100. The fluid storage chamber provides a dedicated volume of fluid that can be used as a fluid source to refill the chamber of bellows pump 102 after each actuation of bellows pump 102.
[0070] In some embodiments, the fluid storage chamber is pre-pressurized before the device 100 is used, such that the fluid inside the fluid storage chamber is at a pressure higher than atmospheric pressure before the bellows pump 102 is first actuated. This increases the amount of fluid stored in the fluid storage chamber, which increases the fluid storage chamber's ability to be refilled by the bellows pump 102. In such embodiments, the pre-pressurized fluid storage chamber is fluid-tight to prevent the pressurized fluid from leaving the chamber before use. In some embodiments, the first valve 105 may be closed before fluid-tightening the pre-pressurized fluid storage chamber.
[0071] Alternatively or additionally, the fluid storage chamber may be constructed of a deformable material. In such an embodiment, the fluid storage chamber can deform to reduce its internal volume as the fluid within it is used until the bellows pump 102 is refilled. This helps prevent the formation of relatively "low" pressure zones within the fluid storage chamber.
[0072] The device 100 in use will now be described. For example... Figure 1 As shown, fluid sample 108, such as a liquid biological specimen, is located within microfluidic channel 101.
[0073] The first valve 105 is closed, and the second valve 106 is open.
[0074] Next, mechanical force is applied to the bellows pump 102. This is in Figure 1 As shown in the image.
[0075] The actuation of the bellows pump 102 reduces the volume of the deformable chamber. This causes the fluid within the bellows pump 102 to be discharged from the second port 104. This forces the fluid sample 108 to move along the microfluidic channel 101.
[0076] Next, the second valve 106 is closed and the first valve 105 is opened. Mechanical force is removed from the bellows pump 102 to allow the deformable chamber to return to its original volume when it fills with fluid from the fluid storage chamber. This results in pressure equalization between the deformable chamber and the fluid storage chamber.
[0077] Advantageously, depending on the requirements of performing specific treatments on the sample, the above steps can then be repeated to actuate the bellows pump once or more to continue moving the fluid sample through the microfluidic channel.
[0078] In this way, the fluid reservoir 107 (in this embodiment, a fluid storage chamber) provides a fluid source to “refill” (also referred to herein as “refill” or “recharge”) the bellows pump 102 after each actuation. This means that the volume of the bellows pump 102, and therefore its footprint on the cartridge, can be reduced because a single actuation of the bellows pump 102 does not need to be able to move the fluid sample through the entire microfluidic channel 101.
[0079] It should be understood that in typical sample handling, based on a predetermined assay procedure, the fluid sample will move through microfluidic channels and multiple regions in several separate steps. This movement of the sample can be performed by appropriate selective actuation of a bellows pump.
[0080] Furthermore, certain steps may involve moving the sample 108 around the microfluidic channel 101 in the opposite direction to that described above. It should be understood that this can be achieved by actuating the bellows pump 102 with the first valve 105 open and the second valve 106 closed.
[0081] Although embodiments of the invention have been described with reference to bellows pumps, it should be understood that in some embodiments, other types of positive displacement pumps, such as syringe pumps, microsyringe pumps, or diaphragm pumps, may be used.
[0082] An injection pump includes a piston that can move within an injection chamber. When the injection pump is actuated, the mechanical force applied to the pump causes the piston to move within the injection chamber, thereby increasing the pressure.
[0083] In some embodiments, the fluid reservoir 107 includes a large region of microfluidic channels adjacent to and connected to the first port 103.
[0084] It should be understood that while some embodiments have been described in the context of diagnostic testing of biological samples, in some embodiments the microfluidic device may perform other types of tests, such as biochemical tests.
[0085] Figure 2 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention. Unless otherwise described and depicted, this device generally corresponds to the reference citation. Figure 1 The device described.
[0086] Device 200 includes a microfluidic channel 201, a positive displacement pump 202, a first port 203 and a second port 204, and a first valve 205 and a second valve 206 for controlling fluid flow through the first port 203 and the second port 204. Device 200 also includes a fluid reservoir. Similar to Reference Figure 1 The described device, the fluid storage unit is the fluid storage chamber 207 of device 200.
[0087] Figure 2 The diagram also illustrates a schematic sample processing area 210. It should be understood that the sample processing area 210 can be arranged in any suitable manner depending on the assay being performed by the apparatus 200. For example, the sample processing area 210 may include one or more filters for separating the portions of the sample, and / or a heating / cooling area for the cartridge.
[0088] The device 200 includes a fluid loop provided by a continuous fluid flow channel extending between a first port 203 and a second port 204 of the positive displacement pump 202. A fluid path is provided along the length of the continuous fluid flow channel.
[0089] In this embodiment, the fluid circuit includes: a first part of the microfluidic channel 201 connecting the second port 204 and the sample processing area 210, the sample processing area 210 itself, a second part of the microfluidic channel 209 connecting the sample processing area 210 and the fluid storage chamber 207, the fluid storage chamber itself 207, and a third part 211 of the microfluidic channel connecting the fluid storage chamber 207 and the first port 203.
[0090] However, it should be understood that, depending on the configuration of the device and the analysis (or multiple analyses) to be performed, various other suitable configurations of the fluid circuit can be used.
[0091] In this way, the fluid storage chamber 207, which serves as a fluid reservoir to provide a fluid source for refilling the positive displacement pump 202, forms part of a continuous fluid loop together with the positive displacement pump 202.
[0092] Advantageously, this arrangement helps prevent back pressure from building up in the fluid storage chamber 207 when the positive displacement pump 202 is repeatedly actuated. This is because each actuation of the positive displacement pump 202 causes the pressure around the fluid circuit to be substantially or partially equalized. Advantageously, this means an increased ability to repeatedly actuate the positive displacement pump 202.
[0093] In some embodiments, the total volume of the continuous fluid loop is approximately 11 ml.
[0094] In some embodiments, the total volume of the fluid storage chamber 207 is approximately 5 ml.
[0095] In some embodiments, the total volume of the chamber of the positive displacement pump 202 is approximately 4 ml.
[0096] Figure 3 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention. Unless otherwise described and depicted, this device generally corresponds to the reference citation. Figure 2 The device described.
[0097] The device 300 includes a microfluidic channel 301, a positive displacement pump 302, a first port 303 and a second port 304, and a first valve 305 and a second valve 306 for controlling the flow of fluid through the first port 303 and the second port 304. The device 300 also includes a fluid storage chamber. Figure 3 The sample processing area 310 is also shown.
[0098] In this embodiment, the fluid storage chamber is the waste storage chamber 307 of the device 300. The waste chamber 307 is arranged to store waste liquid on the device 300. This waste liquid is typically generated during operation of the microfluidic cartridge and may include a sample processing section, which may be mixed with one or more reagents.
[0099] Figure 5 An example of a suitable arrangement for a waste storage room is shown in the figure.
[0100] Waste storage chamber 307 includes a first port 308 and a second port 309. The first port 308 and the second port 309 enable fluid communication between waste storage chamber 307 and other components of device 300.
[0101] Waste storage chamber 307 is connected via a first port 308 and a second port 309, such that it forms part of a continuous fluid flow channel with positive displacement pump 302. When connected in this manner, a fluid communication pathway is provided from positive displacement pump 302 around microfluidic channel 301 through waste storage chamber 307 and back to positive displacement pump 302.
[0102] The first port 308 and the second port 309 extend above the horizontal level of the bottom surface of the chamber 307 within the waste storage chamber 301 (when the device 300 is oriented for use), such that liquid can be stored in the fluid storage chamber 307 below the horizontal level of the first port 308 and the second port 309, and gas (typically air) can be stored in the remaining portion of the waste storage chamber 301 above the liquid.
[0103] In this way, in addition to storing waste liquid, the waste storage chamber 307 is arranged to act as a fluid reservoir by storing a certain volume of fluid (usually air) that can be used to refill the positive displacement pump 302.
[0104] Therefore, waste storage chamber 307 provides dual storage capacity. This reduces the overall size of unit 300. It also means that a separate dedicated fluid storage chamber is not required for refilling the positive displacement pump.
[0105] Now refer to Figures 4A to 4F Describes the device 300 used when a fluid sample moves through a microfluidic channel.
[0106] Figures 4A-4F This shows the usage. Figure 3 A simplified schematic diagram of a microfluidic device. For clarity, Figures 4A-4F Some reference symbols have been omitted.
[0107] Typically, the actions of actuating the positive displacement pump and opening and closing the valves are automatically executed by the mechanical actuator of the main unit based on a pre-programmed sequence.
[0108] Figure 4A The microfluidic device 300 before use is shown.
[0109] like Figure 4A As shown, initially the first valve is closed, and the second valve is open. Biological sample 400 is present in the microfluidic channel.
[0110] Next, as Figure 4B As shown, a positive displacement pump is actuated. A mechanical force is applied to the positive displacement pump, which reduces the volume of the pump chamber, resulting in an increase in pressure within the chamber and forcing the fluid inside to leave the second port and enter the microfluidic channel. This forces the sample 400 to circulate around the microfluidic channel.
[0111] Next, as Figure 4C As shown, the first valve is opened and the second valve is closed. In this configuration, the chamber of the positive displacement pump is prepared to be refilled.
[0112] Next, as Figure 4D As shown, mechanical force is removed from the positive displacement pump. When the chamber is refilled and returned to its previous (i.e., unactuated) volume, fluid is drawn from the fluid reservoir into the chamber of the positive displacement pump.
[0113] Next, as Figure 4E As shown, the first valve is closed and the second valve is opened, causing the positive displacement pump and valve to return to normal. Figure 4A The described startup configuration.
[0114] Then, Figures 4B to 4E The steps can be repeated once or more to move the sample around the microfluidic channel.
[0115] Figure 4F Another actuation of the positive displacement pump is shown. Mechanical force is applied to the positive displacement pump again. The pressure generated by actuating the positive displacement pump causes the fluid sample 400 to move through the microfluidic channel and into the waste chamber.
[0116] Once inside the waste chamber, fluid sample 400 is stored in the lower part of the chamber.
[0117] It should be understood that, if necessary, the fluid sample 400 can be moved in the opposite direction around the microfluidic channel by a reversible valve (i.e., actuating the positive displacement pump when the first valve is open and the second valve is closed).
[0118] In some embodiments, the device 300 is provided with one or more sensors that can detect the presence or absence of liquid at points along a continuous fluid flow path. For example, a liquid sensor may be located at a first port adjacent to the waste chamber. In such embodiments, the presence or absence of liquid can be used to determine the location of a fluid sample within the device. This information can be used by a host device, such as an analyzer, to determine whether to continue actuating the positive displacement pump, for example, if not all fluid samples have been moved into the waste chamber.
[0119] Figure 5 This is a diagram showing a cross-section of a fluid storage chamber according to certain embodiments of the present invention.
[0120] The fluid storage chamber 500 is a waste chamber arranged on the microfluidic cartridge to store waste liquid. This waste liquid is typically generated during the operation of the microfluidic cartridge and may include a biological sample processing section that can be mixed with one or more reagents.
[0121] The fluid storage chamber 500 includes a first port 501 and a second port 502. Ports 501 and 502 extend into the fluid storage chamber 500 such that the port openings are located above the bottom surface of the fluid storage chamber 500. In this way, during use, waste liquid can enter the fluid storage chamber (typically via the first port 501) and be stored in a liquid storage area 503 of the fluid storage chamber 500, which is formed below the horizontal level of the port openings.
[0122] Because the port openings are located above the liquid level in the fluid storage chamber, a fluid path is provided between the first port 501 and the second port 502. In use, when the fluid storage chamber forms part of a continuous fluid loop with the positive displacement pump, the fluid path provides a route for the exchange of gas (typically air) between the first port 501 and the second port 502. This means that negative pressure will not continue to build up downstream of the positive displacement pump whenever it is actuated.
[0123] In this embodiment, ports 501 and 502 are shaped as hollow nails. However, it should be understood that different port shapes and arrangements can be used.
[0124] Figure 6 This is a cross-sectional view showing a valve that can be used in a microfluidic device according to certain embodiments of the present invention.
[0125] The valve is formed along the microfluidic channels of the box in a portion of the microfluidic box body 600.
[0126] The valve includes an inlet 601a and an outlet 601b that are in fluid communication with a microfluidic channel.
[0127] The valve includes a valve seat 602. The valve seat 602 is a material protrusion adjacent to the inlet 601a.
[0128] The valve also includes a flexible membrane layer 603. The membrane layer 603 is fixed to the microfluidic cartridge body 600 to provide a tight fluid seal, which prevents fluid adjacent to the valve from leaking out from the microfluidic channels of the cartridge.
[0129] The diaphragm 603 covers the valve seat 602 and is arranged to be deflected by an external valve actuator to contact the valve seat 602, thereby forming a fluid tight seal between the valve seat 602 and the diaphragm 603.
[0130] Such external valve actuators are typically mechanical actuators of the host unit (in which a microfluidic cartridge containing the valve is inserted).
[0131] In some embodiments, the diaphragm 603 includes a surface recess at a location covering the valve seat 602, where an external valve actuator contacts the diaphragm 603.
[0132] In some embodiments, the membrane 603 is made of a thermoplastic elastomer (TPE) material.
[0133] Figure 7A and Figure 7B Provided in use Figure 6 Another cross-sectional view of the valve.
[0134] Figure 7A The valve is shown in the open position. Figure 7A A mechanical valve actuator 700 is also shown. Figure 7A In this configuration, the valve actuator 700 does not contact the diaphragm 603, thus providing a fluid flow path through the valve.
[0135] Figure 7B The valve is shown in the closed position. Figure 7B In the closed position, valve actuator 700 has come into contact with diaphragm 603, causing diaphragm 603 to deflect and thereby seal against the valve seat. Fluid flow is prevented from passing through the valve in the closed position.
[0136] Figure 8 This is a diagram illustrating a portion of a microfluidic cartridge comprising multiple bellows pumps according to certain embodiments of the present invention.
[0137] The microfluidic cartridge 800 includes a bellows pump 801. The bellows pump 801 is used to drive fluid through a fluid loop around the cartridge 800. Figure 8 The box shown also includes a second bellows pump 802, which generally corresponds to the first bellows pump 801. The second bellows pump 802 can be configured to drive fluid through different fluid loops around the box 800.
[0138] The bellows pump 801 is fluidly connected to the corresponding microfluidic circuit via the inlet and outlet ports.
[0139] The bellows pump 801 includes a generally hemispherical chamber. This chamber is arranged to deform by a mechanical actuator to reduce its volume. This causes fluid (typically air) inside the chamber to be forced out, resulting in fluid flowing around microfluidic channels of the housing 800.
[0140] The chamber of the bellows pump 801 is made of an elastically deformable material. This chamber is elastically biased to return to its unacted shape (and volume) upon actuation. It should be understood that in some embodiments, bellows pumps of other suitable shapes may be used.
[0141] Figure 9 This is a simplified schematic diagram illustrating another microfluidic device according to certain embodiments of the present invention.
[0142] Except as otherwise described and depicted, device 900 generally corresponds to reference 1. Figure 1 The device described.
[0143] The device 900 includes a positive displacement pump 903, a first port 904, a fluid reservoir valve 905, and a fluid reservoir 906. The fluid reservoir 906 is the fluid storage chamber of the device 900.
[0144] Device 900 is different Figure 1 The illustrated device 900 includes more than one microfluidic channel fluidly connected to the positive displacement pump 903. In this embodiment, device 900 includes three microfluidic channels 901a, 901b, and 901c connected to the positive displacement pump 903. However, it should be understood that in some embodiments, device 900 may include two, three, or more than three microfluidic channels connected to the positive displacement pump 903.
[0145] Each microfluidic channel 901a, 901b, 901c includes corresponding valves 902a, 902b, 902c, which are arranged to control the fluid flow between the positive displacement pump 903 and the corresponding channel.
[0146] Device 900 and Figure 1The illustrated device differs in that the positive displacement pump 903 includes a single port 904. Depending on the valve configuration, port 904 can serve as either a fluid inlet or a fluid outlet. More specifically, with microfluidic channel valves 902a, 902b, and 902c closed and fluid reservoir valve 905 open, port 904 serves as a fluid inlet to allow fluid to refill the positive displacement pump 903. With fluid reservoir valve 905 closed and one or more of the microfluidic channel valves 902a, 902b, and 902c open, port 904 serves as a fluid outlet when fluid is forced out of the positive displacement pump 903 and into one or more microfluidic channels 901a, 901b, and 901c, causing fluid to move along the channels.
[0147] Advantageously, in this way, a single positive displacement pump and an associated fluid reservoir 906 can be used to move fluid through multiple microfluidic channels. This can further reduce the footprint of the device 900.
[0148] All features disclosed in this specification (including any appended claims, abstract, and drawings) and / or all steps of any method or process so disclosed may be combined in any combination, except that at least some of such features and / or steps are mutually exclusive combinations. Unless otherwise expressly stated, each feature disclosed in this specification (including any appended claims, abstract, and drawings) may be replaced by an alternative feature for the same, equivalent, or similar purpose. Therefore, unless otherwise expressly stated, each disclosed feature is merely an example of an equivalent or similar feature in a general series. The invention is not limited to the details of the foregoing embodiments. The invention extends to any novel feature or any novel combination of features disclosed in this specification (including any appended claims, abstract, and drawings), or to any novel step or any novel combination of steps of any method or process so disclosed.
[0149] Regarding the general use of any plural and / or singular terms herein, those skilled in the art can adapt the translation of plural to singular and / or singular to plural to the context and / or application. For clarity, various singular / plural permutations may be explicitly described herein.
[0150] Those skilled in the art will understand that, in general, the terms used herein and particularly in the appended claims are generally considered to be “open” terms (e.g., the term “including” should be understood as “including but not limited to,” the term “having” should be understood as “having at least,” the term “includes” should be understood as “including but not limited to,” and so on). Those skilled in the art will also understand that if a particular number in the introduced claim statement is intentional, such intention will be explicitly stated in the claim, and if such a statement is not present, such intention does not exist. For example, to aid understanding, the appended claims may include the use of the introductory phrases “at least one” and “one or more” to introduce the claim statement. However, the use of such phrases should not be construed as implying that a claim statement introduced by the indefinite article "a(a)" or "an(an)" limits any particular claim containing such an introduced claim statement to containing only one embodiment of such a statement, even when the same claim includes the introductory phrase "one or more" or "at least one" and indefinite articles such as "a(a)" or "an(an)" (e.g., "a(a)" and / or "an(an)" should generally be interpreted as meaning "at least one" or "one or more"); the same applies to the use of definite articles used to introduce claim statements. Furthermore, even if a specific number of introduced claim statements is explicitly stated, those skilled in the art will recognize that such a statement should generally be interpreted as meaning at least the number stated (e.g., a plain statement of "two statements" without other modifiers generally means at least two statements or two or more statements).
[0151] It should be understood that various embodiments of this disclosure have been described herein for illustrative purposes, and various modifications may be made without departing from the scope of this disclosure. Therefore, the various embodiments disclosed herein are not intended to be limiting, and the true scope is indicated by the appended claims.
Claims
1. A microfluidic device for moving fluid through a microfluidic channel of the device, the device comprising: Microfluidic channels; A positive displacement pump includes a chamber fluidly connected to the microfluidic channel, wherein the positive displacement pump is arranged such that when the positive displacement pump is actuated, fluid in the chamber is displaced into the microfluidic channel, wherein the device further includes: A fluid reservoir, fluidly connected to the chamber of the positive displacement pump to provide a fluid source for refilling the chamber after the positive displacement pump is actuated, and wherein the fluid reservoir is arranged such that fluid within the fluid reservoir is sealed within the device, wherein the fluid reservoir includes a fluid storage chamber of the device and the fluid storage chamber is a waste chamber arranged on the device to store waste liquid, wherein the device includes a fluid circuit that provides a continuous fluid flow path between the microfluidic channel and the positive displacement pump, the fluid storage chamber being connected such that the fluid storage chamber forms part of the continuous fluid flow path, wherein the fluid storage chamber includes: A first fluid storage chamber port and a further fluid storage chamber port, the fluid storage chambers being connected to the continuous fluid flow channel via the first fluid storage chamber port and the further fluid storage chamber port, wherein the first fluid storage chamber port and the further fluid storage chamber port are hollow pins extending into the fluid storage chamber above the bottom surface of the fluid storage chamber, such that liquid can be stored in the fluid storage chamber below the horizontal level of the first fluid storage chamber port and the further fluid storage chamber port.
2. The apparatus according to claim 1, wherein, The device further includes a first valve and a second valve, the first valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the microfluidic channel, and the second valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the fluid reservoir.
3. The microfluidic device according to claim 2, wherein, At least one of the first valve and the second valve is externally actuable.
4. The microfluidic device according to any one of claims 1-3, wherein, The fluid reservoir comprises a supermajor portion of a microfluidic channel adjacent to the port of the positive displacement pump.
5. The microfluidic device according to any one of claims 1-3, wherein, The positive displacement pump is a bellows pump.
6. The microfluidic device according to claim 4, wherein, The positive displacement pump is a bellows pump.
7. The microfluidic device according to claim 5, wherein, The chamber of the bellows pump is elastically deformable.
8. The microfluidic device according to claim 6, wherein, The chamber of the bellows pump is elastically deformable.
9. The microfluidic device according to any one of claims 1-3 and 6-8, wherein, The microfluidic device is a microfluidic box.
10. The microfluidic device according to claim 4, wherein, The microfluidic device is a microfluidic box.
11. The microfluidic device according to claim 5, wherein, The microfluidic device is a microfluidic box.
12. A method for moving fluid through a microfluidic channel of a microfluidic device, the method comprising the following steps: The positive displacement pump of the microfluidic device is actuated such that the fluid in the chamber of the positive displacement pump is moved into the microfluidic channel, thereby causing the fluid to move through the microfluidic channel; as well as The positive displacement pump chamber is refilled from a fluid source provided by a fluid reservoir of the device, the fluid reservoir being arranged such that fluid within the fluid reservoir is sealed within the device, wherein the fluid reservoir includes a fluid storage chamber of the device and the fluid storage chamber is a waste chamber arranged on the device to store waste liquid, wherein the device includes a fluid circuit that provides a continuous fluid flow channel between the microfluidic channel and the positive displacement pump, the fluid storage chamber being connected such that the fluid storage chamber forms part of the continuous fluid flow channel, wherein the fluid storage chamber includes: a first fluid storage chamber port and a further fluid storage chamber port, the fluid storage chamber being connected to the continuous fluid flow channel via the first fluid storage chamber port and the further fluid storage chamber port, wherein the first fluid storage chamber port and the further fluid storage chamber port are hollow pins extending above the bottom surface of the fluid storage chamber into the fluid storage chamber, such that liquid can be stored in the fluid storage chamber below the horizontal level of the first fluid storage chamber port and the further fluid storage chamber port.
13. The method of claim 12, the apparatus further comprising a first valve and a second valve, the first valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the microfluidic channel, and the second valve being arranged to selectively control fluid flow between the chamber of the positive displacement pump and the fluid reservoir.
14. The method according to claim 13, wherein, The method further includes: Before actuating the positive displacement pump, close the second valve and open the first valve; and Before refilling the chamber, close the first valve and open the second valve.
Citation Information
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