Microfluidic chip apparatus and microfluidic processing system

Abstract

Microfluidic chip apparatus and microfluidic processing system are provided. The microfluidic chip apparatus includes a shell, a circuit board, a conductive foam gasket over the circuit board, and a microfluidic chip over the conductive foam gasket. The shell has injection track(s). The microfluidic chip includes a top plate formed of a conductive material and a microelectrode dot array below the top plate, and a space is defined therebetween. The conductive foam gasket and top plate extend beyond side(s) of the microelectrode dot array and contact each other. The injection track(s) is / are connected to the space so that droplet(s) can be injected through the injection track(s). The microfluidic processing system includes the microfluidic chip apparatus and a control apparatus.

Description

Technical Field

[0001] This invention relates to a microfluidic chip device and a microfluidic processing system. Specifically, this invention relates to a microfluidic chip device and a microfluidic processing system that combines real-time sensing technology with microbead stabilization technology. Prior Technology

[0002] Compared to traditional biomedical testing equipment, using digital microfluidic biochips (DMFB) for biomedical testing (e.g., protein analysis, disease diagnosis) offers numerous advantages, such as miniaturization of the testing equipment, reduced reaction volume for analysis and testing, reduced sample and reagent usage, lower testing costs, and automation of laboratory biomedical testing. In particular, DMFB with microelectrode arrays achieves excellent analytical results in many biomedical tests (e.g., nucleic acid-based assays, drug assays). DMFB utilizes electrowetting-on-dielectric (EWOD) technology for microfluidic manipulation, enabling automation of laboratory biomedical testing. Currently, there are DMFBs custom-designed for specific biomedical testing projects, as well as DMFBs and related systems adaptable to various biomedical testing projects.

[0003] Regardless of the type of digital microfluidic chip used for biomedical testing, precise control of the volume of microbeads (e.g., test samples, reagents, buffer solutions) injected into the digital microfluidic chip is essential for obtaining accurate test results. However, conventional microbead injection techniques face two main challenges. First, the current common practice involves users manually injecting microbeads into the digital microfluidic chip using an injection device (e.g., a syringe). This manual injection mechanism heavily relies on the user's experience, easily leading to inconsistent microbead volumes depending on the user, thus affecting the accuracy of subsequent tests. Second, the upper and lower surfaces of the space used to hold the microbeads in a digital microfluidic chip are often hydrophobic, while the injection tip of the injection device (e.g., a needle) is hydrophilic. These characteristics both increase the difficulty of separating the microbeads from the injection device and injecting them into the digital microfluidic chip.

[0004] In view of this, there is an urgent need in the field for a technology that can easily, stably and accurately inject microbeads of the required volume into digital microfluidic chips, so as to improve the accuracy of biomedical testing results by improving the injection accuracy. Summary of the Invention

[0005] One object of the present invention is to provide a microfluidic chip device comprising a housing, a circuit board, a conductive foam, and a microfluidic chip. The housing has at least one injection track. The conductive foam is configured to be placed above the circuit board. The microfluidic chip is configured to be placed above the conductive foam. The microfluidic chip includes a top plate and a microelectrode array, wherein the top plate is formed of a conductive material, the microelectrode array is disposed below the top plate, and a space is defined between the top plate and the microelectrode array. The conductive foam and the top plate extend beyond at least one side of the microelectrode array and are in contact with each other. The at least one injection track is connected to the space, allowing at least one microbead to be injected into the space via the at least one injection track.

[0006] In some embodiments, the microelectrode array includes a plurality of microelectrode elements connected in series, each microelectrode element being configured to read a corresponding sample operation setting in a first time interval, the conductive foam being configured to conduct electricity in a second time interval to give the top plate a preset voltage level, and each microelectrode element being further configured to enter a sample control state in the second time interval according to the corresponding sample operation setting.

[0007] In some embodiments, the microelectrode elements are divided into an injection control region and a non-injection control region. The sample operation settings read by the microelectrode elements corresponding to the injection control region are configured to operate the microelectrode elements corresponding to the injection control region during the second time interval, while the sample operation settings read by the microelectrode elements corresponding to the non-injection control region are configured to not operate the microelectrode elements corresponding to the non-injection control region during the second time interval.

[0008] In some implementations, the injection control region is adjacent to the at least one injection track.

[0009] In some embodiments, the microelectrode array includes a plurality of microelectrode elements connected in series, which are configured to detect a plurality of capacitance values ​​between the top plate and the microelectrode elements one-to-one in a first time interval, and the microelectrode elements are further configured to output the capacitance values ​​one-to-one in a plurality of sub-time intervals in a second time interval.

[0010] Another object of the present invention is to provide a microfluidic processing system. The microfluidic processing system includes a control device and a microfluidic chip device, the microfluidic chip device being electrically connected to the control device. The microfluidic chip device includes a first housing, a first circuit board, a conductive foam, and a microfluidic chip. The first housing has at least one injection track. The conductive foam is configured to be placed above the first circuit board. The microfluidic chip is configured to be placed above the conductive foam and includes a top plate and a microelectrode array, wherein the top plate is formed of a conductive material, the microelectrode array is disposed below the top plate, and a space is defined between the top plate and the microelectrode array. The conductive foam and the top plate extend beyond at least one side of the microelectrode array and are in contact with each other. The at least one injection track is connected to the space, allowing at least one microbead to be injected into the space via the at least one injection track.

[0011] In some embodiments, the microelectrode array includes a plurality of microelectrode elements connected in series. The control device is configured to provide a plurality of sample operation settings in a first time interval, and the microelectrode elements are configured to read the sample operation settings one-to-one in the first time interval. The conductive foam is configured to conduct electricity in a second time interval to give the top plate a preset voltage level, and each microelectrode element is further configured to enter a sample control state in the second time interval according to the corresponding sample operation setting.

[0012] In some embodiments, the microelectrode elements are divided into an injection control region and a non-injection control region. The sample operation settings read by the microelectrode elements corresponding to the injection control region are configured to operate the microelectrode elements corresponding to the injection control region during the second time interval, while the sample operation settings read by the microelectrode elements corresponding to the non-injection control region are configured to not operate the microelectrode elements corresponding to the non-injection control region during the second time interval.

[0013] In some implementations, the injection control region is adjacent to the at least one injection track.

[0014] In some embodiments, the microelectrode elements are configured to detect a plurality of capacitance values ​​between the top plate and the microelectrode elements one-to-one in a first time interval, the microelectrode elements are further configured to output the capacitance values ​​one-to-one in a plurality of sub-time intervals in a second time interval, and the control device is configured to receive the capacitance values ​​in the second time interval.

[0015] In some embodiments, the control device is further configured to determine a size and a position of each of the at least one microbead between the top plate and the microelectrode array based on the capacitance values.

[0016] In some embodiments, the control device is further configured to transmit the capacitance values ​​to a computing device, so that the computing device determines a size and a position of each of the at least one microbead between the top plate and the microelectrode array based on the capacitance values.

[0017] In some embodiments, the microfluidic processing system further includes a second circuit board and a second housing. The second circuit board is electrically connected to the control device and the microfluidic wafer device. The second housing is configured to house the control device and the second circuit board.

[0018] The following detailed description of the technology and implementation methods of the present invention, in conjunction with the accompanying drawings, is intended to enable those skilled in the art to understand the technical features of the claimed invention. Simple Explanation of the Diagram

[0019] Figure 1A depicts a side cross-sectional view of a microfluidic wafer device in some embodiments.

[0020] Figure 1B depicts a side cross-sectional view of a microfluidic wafer device in some other embodiments.

[0021] Figure 1C depicts a top perspective view of a microfluidic wafer device in some of the embodiments.

[0022] Figure 1D depicts an exploded view of the microfluidic wafer device in Figure 1C.

[0023] Figure 1E depicts a partial cross-sectional view of the microfluidic wafer device in Figure 1C taken along line II.

[0024] Figure 2A depicts a side view of a microfluidic wafer in some embodiments.

[0025] Figure 2B depicts a top view of a microfluidic wafer in some embodiments.

[0026] Figure 2C depicts a circuit block diagram of a microelectrode element in some embodiments.

[0027] Figure 2D depicts a top view of a microfluidic wafer in some other embodiments.

[0028] Figure 2E depicts a circuit block diagram of a microelectrode element in some other embodiments.

[0029] Figure 3 depicts a schematic diagram of the architecture of a microfluidic processing system.

[0030] Figure 4A depicts sample operation settings presented using a sample control pattern.

[0031] Figure 4B depicts an exemplary timing diagram.

[0032] Figure 4C depicts a schematic diagram of the injection control region and the non-injection control region.

[0033] Figure 5 depicts a schematic diagram of a miniaturized microfluidic processing system in one embodiment. Implementation

[0034] The following will explain the microfluidic chip device and microfluidic processing system provided by the present invention through embodiments. However, these embodiments are not intended to limit the implementation of the present invention to any environment, application, or manner described in these embodiments. Furthermore, without departing from the spirit of the present invention, the specific features, structures, and / or characteristics described in these embodiments can be combined in any suitable combination and / or sub-combination. Therefore, the description of the following embodiments is only for illustrating the purpose of the present invention and is not intended to limit the scope of the present invention. It should be understood that in the following embodiments and drawings, elements not directly related to the present invention have been omitted and are not shown. In addition, the dimensions of the elements and the proportional relationships between the elements in the drawings are only for illustration and explanation and are not intended to limit the scope of the present invention. Furthermore, unless otherwise stated, the terms "a," "the," and similar terms used in this specification and the claims should be understood to include both singular and plural forms.

[0035] [Microfluidic wafer device] [hardware] [Architecture]

[0036] Figure 1A depicts a schematic diagram of a microfluidic wafer device 1001 according to some embodiments of the present invention. The microfluidic wafer device 1001 includes a housing 100, a circuit board 401, a conductive foam 303, and a microfluidic wafer 300, wherein the conductive foam 303 is configured to be placed above the circuit board 401, and the microfluidic wafer 300 is configured to be placed above the conductive foam 303.

[0037] The microfluidic chip 300 includes a top plate 301 and a microelectrode array 302, wherein the microelectrode array 302 is disposed below the top plate 301, and a space SP is defined between the top plate 301 and the microelectrode array 302. The top plate 301 is formed of a conductive material (e.g., an indium tin oxide (ITO) glass plate). The conductive foam 303 and the top plate 301 extend beyond at least one side of the microelectrode array 302 and are in contact with each other. Therefore, when the conductive foam 303 is conductive, the top plate 301 will have a preset voltage level, which, under the action of dielectric wetting technology, generates sufficient force to stabilize or drive the microbeads located in the space SP (described in detail later).

[0038] Furthermore, the housing 100 has an injection track 103, which is connected to the space SP. Therefore, at least one microbead LO can be injected into the space SP via the injection track 103 and can move within the space SP. By providing the injection track 103 on the housing 100, the user can easily and stably inject the microbead LO into the space SP. It should be noted that although only one injection track is shown in Figure 1A, it should be understood that the present invention does not limit the number of injection tracks provided on the housing 100, as long as the housing 100 has at least one injection track.

[0039] Figure 1B depicts a schematic diagram of a microfluidic wafer device 1001' according to some other embodiments of the present invention. The microfluidic wafer device 1001' includes a housing 100', a circuit board 401, a conductive foam 303, and a microfluidic wafer 300, wherein the conductive foam 303 is configured to be placed above the circuit board 401, and the microfluidic wafer 300 is configured to be placed above the conductive foam 303.

[0040] The main difference between the microfluidic wafer device 1001' shown in Figure 1B and the microfluidic wafer device 1001 shown in Figure 1A lies in the arrangement of the injection track on the housing. In Figure 1B, the top plate 301 has a hole, and in accordance with this configuration, the housing 100' has an injection track 103' above the hole, and the injection track 103' communicates with the space SP. In this configuration, since the injection track 103' is connected to the space SP, the user can easily and stably inject microbeads LO into the space SP. It should be noted that although Figure 1B only shows one injection path (i.e., formed by a hole in the top plate and the injection track above the hole), it should be understood that the present invention does not limit the number of injection paths, as long as there is at least one injection path.

[0041] Figures 1C to 1E depict schematic diagrams of a microfluidic wafer device 1001'' in some embodiments of the present invention, wherein Figure 1C is a top perspective view of the microfluidic wafer device 1001'', Figure 1D is an exploded view of the microfluidic wafer device 1001'', and Figure 1E is a partial cross-sectional view taken along line II of Figure 1C.

[0042] The microfluidic chip device 1001'' includes a housing 100'', a circuit board 401, a conductive foam 303, and a microfluidic chip 300, wherein the conductive foam 303 is configured to be placed above the circuit board 401, and the microfluidic chip 300 is configured to be placed above the conductive foam 303. Furthermore, the housing 100'' has two injection tracks 103a and 103b.

[0043] The housing 100'' in the embodiments shown in Figures 1C to 1E includes a base 101 and a cover 102. The cover 102 can fix the microfluidic wafer 300 above the top plate 301. The base 101 has a base 101B and three walls 101L, 101W, and 101R. The base 101B and the walls 101L, 101W, and 101R define a receiving area 111, into which at least a portion of the circuit board 401 is adapted to be embedded. In the embodiments shown in Figures 1C to 1E, injection tracks 103a and 103b are disposed on the wall 101W. As shown in Figure 1E, when at least a portion of the circuit board 401 is embedded in the receiving area 111 of the base 101, the injection tracks 103a and 103b are connected to the space SP, so at least one microbead can be injected into the space SP via the injection tracks 103a and / or 103b.

[0044] In some embodiments, when at least a portion of the circuit board 401 is embedded in the receiving area 111 of the seat 101, one side of the microfluidic chip 300 abuts against the inner side of the wall 101W having injection tracks 103a and 103b, so that the injection tracks 103a and 103b are in close proximity to the injection space SP, so that the injected microbeads do not overflow outside the microfluidic chip 300.

[0045] In some embodiments, the injection track 103a has a non-zero angle a1 with a horizontal axis HL, and the injection track 103b also has a non-zero angle a2 with the horizontal axis HL (as shown by the dashed circle in Figure 1E). Since the arrangement of the injection tracks 103a and 103b inclined to the horizontal axis HL is more in line with the angle at which the user operates the injection device, it helps to improve the stability of the user's operation of the injection device and also allows the microspheres to enter the space SP more smoothly from the inclined injection track 103a and / or injection track 103b.

[0046] In some embodiments, injection tracks 103a and 103b each have an injection channel 106a and 106b on their inner sides near the wall 101W, and the radii of injection channels 106a and 106b are smaller than the radii of injection tracks 103a and 103b, respectively. In these embodiments, when at least a portion of the circuit board 401 is embedded in the receiving area 111 of the seat 101, the injection channels 106a and 106b are adjacent to and communicate with the space SP defined by the top plate 301 and the microelectrode array 302. Therefore, when the injection device is a syringe, the syringe barrel can be placed on the injection tracks 103a and 103b, and the syringe needle can be placed on the injection channels 106a and 106b, making the injection device more stable and allowing the microbeads to be injected more smoothly into the space SP.

[0047] In some embodiments, the receiving area 111 extends to the lower half of the wall 101W, and this extended area is located below the injection tracks 103a and 103b. In these embodiments, when at least a portion of the circuit board 401 is embedded in the receiving area 111 of the seat 101, a portion 401a of the circuit board 401 is embedded in the extended area, and one side of the microfluidic wafer 300 abuts against the inner side of the wall 101W having the injection tracks 103a and 103b. This provides greater stability to the microfluidic wafer 300, the conductive foam 303, and the circuit board 401, preventing injected microbeads from spilling outside the microfluidic wafer 300.

[0048] [Structure of microfluidic wafers]

[0049] The following description will continue using microfluidic wafer device 1001 as an example. However, it should be understood that the following description also applies to microfluidic wafer device 1001', microfluidic wafer device 1001'', and other microfluidic wafer devices that conform to the spirit of the present invention.

[0050] In some embodiments, the microfluidic chip 300 included in the microfluidic chip device 1001 has a special structure, which allows the microfluidic chip device 1001 to be used with a control device and a computing device. Under the control of the computing device and the control device, the process of injecting microbeads into the microfluidic chip 300 is easier, more stable and more precise (details to follow). The structure of the microfluidic chip 300 in some embodiments is now described.

[0051] In some embodiments, the microfluidic chip 300 may be the microfluidic chip disclosed in Republic of China (Taiwan) Patent Application No. 112109315, filed on March 14, 2023, the full text of which is incorporated herein by reference.

[0052] In these embodiments, the side and top views of the microfluidic wafer 300 are depicted in Figures 2A and 2B, respectively. The microfluidic wafer 300 includes a top plate 301 and a microelectrode array 302, wherein the microelectrode array 302 is disposed below the top plate 301, defining a space SP between the top plate 301 and the microelectrode array 302, and at least one microbead LO can be injected into the space SP and move within the space SP. In some embodiments, the microfluidic wafer 300 may further include two hydrophobic layers 22 and 24, wherein the hydrophobic layer 22 is disposed below the top plate 301 and in direct contact with the top plate 301, and the hydrophobic layer 24 is disposed above the microelectrode array 302, and the aforementioned space SP for microbead movement can be defined by the hydrophobic layers 22 and 24. The hydrophobic layers 22 and 24 may be formed of a material with hydrophobic properties.

[0053] The microelectrode array 302 includes a plurality of microelectrode elements 1 connected in series, and these microelectrode elements 1 are arranged in a scale of [missing information]. A two-dimensional array, in which and All are positive integers greater than 1. The computing device also knows that these microelectrode elements 1 are arranged in a scale of A two-dimensional array. Each microelectrode element 1 includes a microfluidic electrode 11, a multifunctional electrode 13 (which, depending on the operation performed, can serve as a heating electrode, an insulating layer, or a magnetic field providing layer), and a control circuit 15. Each microfluidic electrode 11 is disposed below the top plate 301, each multifunctional electrode 13 is disposed below the corresponding microfluidic electrode 11 (i.e., the microfluidic electrode 11 belonging to the same microelectrode element 1), and each control circuit 15 is disposed below the corresponding multifunctional electrode 13 (i.e., the multifunctional electrode 13 belonging to the same microelectrode element 1). In some embodiments, the microelectrode array 302 may further include a microelectrode interface 20 disposed above the microelectrode elements 1 and below the hydrophobic layer 24. The microelectrode interface 20 is used to interface the hydrophobic layer 24 and may be a silicon dioxide (SiO2) insulating layer.

[0054] The present invention does not limit the size of each microelectrode element 1 to any specific size. However, in some embodiments, the area of ​​the upper surface of each microelectrode element 1 may be approximately 2,500 square micrometers (μm²). Furthermore, the present invention also does not limit the spacing between these microelectrode elements 1 to any specific value. In some embodiments, the spacing between one microelectrode element 1 and another microelectrode element 1 may be approximately 1 micrometer (μm).

[0055] Each square in Figure 2B represents a microelectrode element 1. Each microelectrode element 1 has two input terminals (i.e., a first input terminal and a second input terminal) and two output terminals (i.e., a first output terminal and a second output terminal). The microelectrode elements 1 are connected in series in a manner that forms a first input / output chain and a second input / output chain. The first input terminals of each microelectrode element 1 other than the first microelectrode element 1 are coupled to the first output terminal of the preceding microelectrode element 1, thereby forming the first input / output chain. In this way, the microelectrode elements 1 other than the first microelectrode element 1 receive input signals DI1 (e.g., sample operation setting S2) through one or more microelectrode elements 1 arranged in front, while the microelectrode elements 1 other than the last microelectrode element 1 provide output signals DO1 (e.g., stored capacitance value C1) through microelectrode elements 1 arranged behind. Similarly, the second input terminals of each microelectrode element 1 other than the first microelectrode element 1 are coupled to the second output terminal of the preceding microelectrode element 1, thereby forming the second input / output chain. In this way, each microelectrode element 1 other than the first microelectrode element 1 receives input signal DI2 (e.g., heating control setting S1, magnetic field control setting S3) through one or more microelectrode elements 1 arranged in front, while each microelectrode element 1 other than the last microelectrode element 1 provides output signal DO2 (e.g., stored capacitance value) through microelectrode elements 1 arranged behind.

[0056] In these embodiments, the circuit block diagram of each microelectrode element 1 can be depicted as shown in Figure 2C. Each microelectrode element 1 includes a microfluidic electrode 11, a multifunctional electrode 13, and a control circuit 15. The control circuit 15 of each microelectrode element 1 includes a microfluidic control and position sensing circuit 151, a temperature and magnetic field control circuit 153, and two storage circuits 155 and 157. In each microelectrode element 1, the microfluidic control and position sensing circuit 151 is coupled to the microfluidic electrode 11 and the storage circuit 155, and the temperature and magnetic field control circuit 153 is coupled to the multifunctional electrode 13 and the storage circuit 157. For each microelectrode element 1, the first input terminal and the first output terminal belong to the storage circuit 155, while the second input terminal and the second output terminal belong to the storage circuit 157. This means that the first input / output chain is formed by connecting the storage circuits 155, and the second input / output chain is formed by connecting the storage circuits 157.

[0057] Each microfluidic control and position sensing circuit 151 can receive a sample control signal (also referred to as a microfluidic control signal) EN_F and perform sample operations on the microspheres accordingly, and can receive a position sensing signal EN_S and sense the capacitance value between the top plate 301 and the microelectrode element 1 accordingly. Each storage circuit 155 can receive a clock signal CLK1 and receive and store an input signal DI1 (e.g., sample operation setting S2), and / or provide an output signal DO1 (e.g., stored capacitance value C1). Each temperature and magnetic field control circuit 153 can receive a heating control signal EN_T and heat the multifunctional electrode 13 accordingly, and can receive a magnetic field control signal EN_M and provide a magnetic field for the multifunctional electrode 13 accordingly. Each storage circuit 157 can receive a clock signal CLK2 and receive and store an input signal DI2 (e.g., heating control setting S1, magnetic field control setting S3), and / or provide an output signal DO2 (e.g., stored capacitance value).

[0058] In some embodiments, the microfluidic chip 300 may be the microfluidic chip disclosed in Republic of China (Taiwan) Patent Application No. 110119564 filed on May 28, 2021, or the microfluidic chip disclosed in Republic of China (Taiwan) Patent Application No. 111101835 filed on January 17, 2022, the full text of which is incorporated herein by reference.

[0059] In these embodiments, the side and top views of the microfluidic wafer 300 are depicted in Figures 2A and 2D, respectively. Each square in Figure 2D represents a microelectrode element 1. Compared to Figure 2B, each microelectrode element 1 in Figure 2D has an input terminal and an output terminal. The input terminals of each microelectrode element 1 other than the first microelectrode element 1 are coupled to the output terminal of the preceding microelectrode element 1. In this way, each microelectrode element 1 other than the first microelectrode element 1 receives an input signal DI (e.g., heating control setting S1, sample operation setting S2) through one or more microelectrode elements 1 arranged in front, while each microelectrode element 1 other than the last microelectrode element 1 provides an output signal DO (e.g., the stored capacitance value C1) through microelectrode elements 1 arranged behind.

[0060] In these embodiments, the circuit block diagram of each microelectrode element 1 can be depicted as shown in Figure 2E. Each microelectrode element 1 includes a microfluidic electrode 11, a multifunctional electrode 13, and a control circuit 15, and the control circuit 15 of each microelectrode element 1 includes a microfluidic control and position sensing circuit 151, a temperature control circuit 153', and a storage circuit 155. Each microfluidic control and position sensing circuit 151 is coupled to the corresponding microfluidic electrode 11 (i.e., the microfluidic electrode 11 belonging to the same microelectrode element 1), and each temperature control circuit 153' is coupled to the corresponding multifunctional electrode 13 (i.e., the multifunctional electrode 13 belonging to the same microelectrode element 1). The microfluidic control and position sensing circuit 151, the temperature control circuit 153', and the storage circuit 155 in the same microelectrode element 1 are coupled to each other. Each microfluidic control and position sensing circuit 151 can receive a sample control signal EN_F and perform sample operations on the microspheres accordingly, and can receive a position sensing signal EN_S and sense the capacitance value between the top plate 301 and the microelectrode element 1 accordingly. Each storage circuit 155 can receive a clock signal CLK1 and receive and store input data DI (e.g., heating control setting S1, sample operation setting S2), and / or provide output data DO (e.g., the stored capacitance value C1). Each temperature control circuit 153' can receive a heating control signal EN_T and cause the multifunctional electrode 13 to heat.

[0061] Microfluidic processing system

[0062] In some embodiments, the microfluidic chip device 1001 can be used in conjunction with a control device 1002 and a computing device 1003 to form a microfluidic processing system 1000, as shown in Figure 3. With the control of the control device 1002 and the computing device 1003, the process of injecting microbeads into the microfluidic chip 300 will be easier, more stable and more precise.

[0063] Figure 3 depicts a schematic diagram of the architecture of the microfluidic processing system 1000. The microfluidic processing system 1000 includes a microfluidic chip device 1001, a control device 1002, and a computing device 1003. The control device 1002 may be a single-board computer, such as a Raspberry Pi. The computing device 1003 may be a smart mobile device, a notebook computer, a desktop computer, a server, or other computing-capable devices known to those skilled in the art to which this invention pertains. The computing device 1003 is electrically connected to the control device 1002, and the communication method between them includes one or more of the following: wireless transmission technology (e.g., Bluetooth, Wi-Fi), wired transmission technology (e.g., data cable), and other communication technologies or devices known to those skilled in the art to which this invention pertains. The control device 1002 is electrically connected to the microfluidic chip device 1001, and the communication method between the two includes one or more of the following: wireless transmission technology (e.g., Bluetooth, Wi-Fi), wired transmission technology (e.g., transmission line), and other communication technologies or devices known to those skilled in the art to which this invention pertains.

[0064] Next, we will describe the operations that can be performed by the microfluidic wafer device 1001, the control device 1002, and the computing device 1003, which are more relevant to the stable injection of microbeads.

[0065] [Apply sample manipulation to stabilize microbeads in a microfluidic wafer]

[0066] The computing device 1003 can control the microfluidic chip 300 through the control device 1002 to apply sample operations (e.g., stabilizing one or more microbeads, moving one or more microbeads, cutting microbeads, mixing microbeads) to one or more microbeads in the microfluidic chip 300. The following will explain how to stabilize microbeads in the microfluidic chip 300 by applying sample operations.

[0067] The computing device 1003 can generate a plurality of sample operation settings S2 according to a sample operation requirement (e.g., stabilizing the microbeads in a designated position), wherein each sample operation setting S2 corresponds one-to-one with the microelectrode elements 1. Each sample operation setting is read by the corresponding microelectrode element 1 (e.g., through the storage circuit 155 in Figures 2C and 2E), and each sample operation setting is used to instruct the corresponding microelectrode element 1 (e.g., through the microfluidic control and position sensing circuit 151 in Figures 2C and 2E) to enter a sample control state (i.e., active or inactive) corresponding to the sample operation setting within a sample operation time interval.

[0068] Figure 4A illustrates the sample operation settings S2 using a sample control pattern CP1, but its specific content is not intended to limit the scope of the invention. In Figure 4A, Each square represents The data read by each microelectrode element 1 Each sample operation setting (e.g., read in via storage circuit 155 in Figures 2C and 2E) represents an "operation" state, and each white square represents a "non-operation" state. For example, the sample operation setting corresponding to a white square can be a value of 0, while the sample operation setting corresponding to a gray square can be a value of 1.

[0069] The computing device 1003 transmits the sample operation settings S2 to the control device 1002, which then provides the sample operation settings S2 to the microfluidic chip 300. Please refer to the exemplary timing diagram shown in Figure 4B, but it is not intended to limit the scope of the invention. The computing device 1003, through the control device 1002, enables the clock signal CLK1 to the microfluidic chip 300 in a plurality of sub-time intervals within the time interval T1 (e.g., the voltage level of the clock signal CLK1 is high in these sub-time intervals of time interval T1). These sub-time intervals within the time interval T1 correspond one-to-one with the microelectrode elements 1. If the microelectrode array 302 includes... If there is one microelectrode element 1, then the time interval T1 has Each sub-time interval. Thus, when the control device 1002 provides the sample operation settings S2 within time interval T1, the microelectrode elements 1 will read the corresponding sample operation settings S2 within each sub-time interval of time interval T1. This invention does not limit the clock frequency of the clock signal CLK1. For example, the control circuit 15 can read the sample operation settings S2 when the clock frequency of the clock signal CLK1 is set to 100 kHz.

[0070] The computing device 1003 provides a sample control signal EN_F to the microfluidic chip 300 via the control device 1002, and the sample control signal EN_F is enabled during a time interval T2 (e.g., during time interval T2, the voltage level of the sample control signal EN_F is at a high level). Time interval T2 follows time interval T1. Additionally, the conductive foam 303 can receive a voltage signal VS, and the voltage signal VS is at a preset voltage level during time interval T2, thus causing the top plate 301 to have that preset voltage level during time interval T2. Time interval T2 is the aforementioned sample operation time interval. During time interval T2, the sample control signal EN_F is enabled and the top plate 301 has the preset voltage level. Therefore, each microelectrode element 1 will enter a sample operation state (i.e., active or inactive) during time interval T2 according to the corresponding sample operation setting. The activated microelectrode element 1 generates sufficient force to attract the microbeads under the action of dielectric wetting technology. In this way, the activated microelectrode element 1 can stabilize the microbeads within the time interval T2.

[0071] Furthermore, in some embodiments, the aforementioned mechanism for applying sample operations to stabilize microbeads in a microfluidic wafer can be implemented during the process of injecting microbeads into the microfluidic wafer 300. In these embodiments, the microelectrode elements 1 are divided into an injection control region CA and a non-injection control region NCA, which means that the sample operation settings S2 read by the microelectrode elements 1 are also divided into the injection control region CA and the non-injection control region NCA, as shown in Figure 4A. In these embodiments, the injection control region CA may be adjacent to at least one injection track on the sidewall (e.g., injection track 103a and / or injection track 103b).

[0072] In these embodiments, the sample operation settings read by the microelectrode elements 1 corresponding to the injection control region CA are such that the microelectrode elements 1 corresponding to the injection control region CA are activated during time interval T2, while the sample operation settings read by the microelectrode elements 1 corresponding to the non-injection control region NCA are such that the microelectrode elements 1 corresponding to the non-injection control region NCA are not activated during time interval T2. As mentioned above, the activated microelectrode elements 1 will generate sufficient force to attract the microbeads under the action of dielectric wetting technology. In this way, the activated microelectrode elements 1 can stabilize the injected microbeads in the injection control region CA adjacent to the injection track within time interval T2.

[0073] [Positioning Microbeads]

[0074] The microfluidic processing system 1000 can detect each microbead in the microfluidic chip 300 (specifically, in the space SP of the microfluidic chip 300) and position each microbead in the microfluidic chip 300 (i.e., determine the size and position of each microbead in the microfluidic chip 300). Through the positioning mechanism, if the microbeads in the microfluidic chip 300 are positioned during the injection process, it can be determined whether the microbeads have been accurately injected into the microfluidic chip 300.

[0075] Please refer to the exemplary timing diagram shown in Figure 4B. The computing device 1003 provides a position sensing signal EN_S to the microfluidic chip 300 via the control device 1002, and the position sensing signal EN_S is enabled for a time interval T3 (e.g., the voltage level of the position sensing signal EN_S is high during time interval T3). Since the position sensing signal EN_S is enabled during time interval T3, each microelectrode element 1 detects the capacitance value between the top plate 301 and itself during time interval T3 (e.g., through the microfluidic control and position sensing circuit 151 in Figures 2C and 2E); specifically, each microelectrode element 1 detects the capacitance value between the top plate 301 and the microfluidic electrode 11 it contains during time interval T3. The magnitude of each capacitance value C1 reflects whether there is liquid between the top plate 301 and the corresponding microelectrode element 1 (more specifically, between the top plate 301 and the corresponding microfluidic electrode 11). If the detected capacitance value is represented by the values ​​0 and 1, then the value 1 can represent that there is liquid between the top plate 301 and the microelectrode element 1 (more specifically, between the top plate 301 and the microfluidic electrode 11), while the value 0 can represent that there is no liquid between the top plate 301 and the microelectrode element 1 (more specifically, between the top plate 301 and the microfluidic electrode 11).

[0076] Additionally, the computing device 1003 enables a plurality of sub-time intervals within a time interval T4 via a clock signal CLK1 provided by the control device 1002 (e.g., the voltage level of the clock signal CLK1 is high during these sub-time intervals of time interval T4). Time interval T4 follows time interval T3. These sub-time intervals within time interval T4 correspond one-to-one with the microelectrode elements 1. If the microelectrode array 302 includes... If there is one microelectrode element 1, then the time interval T4 has Each sub-time interval. Since the clock signal CLK1 is enabled during these sub-time intervals of time interval T4, the microelectrode elements 1 will output the capacitance value C1 during each of these sub-time intervals of time interval T4 (e.g., through the storage circuit 155 in Figures 2C and 2E). This invention does not limit the clock frequency of the clock signal CLK1. For example, the control circuit 15 can output the capacitance value C1 when the clock frequency of the clock signal CLK1 is set to 100 kHz.

[0077] Control device 1002 receives the capacitance value C1 from microfluidic wafer 300 and transmits the capacitance value C1 to computing device 1003. Computing device 1003 knows that the microelectrode elements 1 are arranged in a scale of... The computing device 1003 can calculate the size and position of each microbead in the microfluidic wafer 300 based on the capacitance value C1, given that the two-dimensional array of the microbeads corresponds one-to-one with each microelectrode element 1. This allows the computing device 1003 to determine whether the microbeads are accurately injected into the microfluidic wafer 300 and further decide whether related control is required.

[0078] For ease of understanding, Figure 4A also shows the size and position of the microbeads LO as determined by the computing device 1003 based on the capacitance value C1. Figure 4A clearly shows that the injected microbeads LO are stabilized in the injection control zone CA adjacent to the injection track.

[0079] [Real-time sensing and feedback]

[0080] In some embodiments, the computing device 1003 may store a testing specification corresponding to a biomedical procedure, and the testing specification may include the sample size required for the biomedical procedure, the dosage of the required reagents, and / or other requirements that the biomedical test must follow.

[0081] In these embodiments, after calculating the size and position of the microbeads LO based on the capacitance values ​​C1, the computing device 1003 can determine whether the volume of the microbeads LO in the microfluidic chip 300 meets the required testing specifications (e.g., if the microbeads LO are a sample, whether their volume has reached the specified sample amount; or, if the microbeads LO are a reagent, whether their volume has reached the specified dosage). If the volume of the microbeads LO in the microfluidic chip 300 meets the requirements of the testing specifications, the computing device 1003 can issue a termination message to remind the user to stop injecting microbeads into the space SP. Conversely, if the computing device 1003 determines based on the capacitance values ​​C1 that the volume of the microbeads LO in the microfluidic chip 300 has not yet reached the amount specified in the testing specifications, the computing device 1003 can send a prompt message to remind the user to continue injecting microbeads into the space SP.

[0082] Furthermore, the computing device 1003 can adjust the injection control area CA (e.g., increase the range of the injection control area CA, as shown in the sample control pattern CP2 in Figure 4C), generate sample operation settings based on the adjusted injection control area CA, and provide the adjusted sample operation settings to the microfluidic chip 300 through the control device 1002, so that the microfluidic chip 300 applies sample operations to the microbeads LO according to the adjusted sample operation settings. In this way, when the user continuously injects microbeads into the space SP, the microfluidic chip 300 more accurately stabilizes the continuously injected microbeads according to the adjusted sample operation settings. Similarly, the microfluidic chip 300 can detect capacitance values ​​again and output the re-detected capacitance values, allowing the computing device 1003 to make another judgment. The aforementioned process can be repeated multiple times until the computing device 1003 determines, based on the capacitance values, that the volume of the microbeads LO in the microfluidic chip 300 reaches the amount specified in the detection standard. Those skilled in the art to which this invention pertains can understand from the foregoing description how the computing device 1003, the control device 1002, and the microfluidic wafer 300 repeatedly operate to achieve the volume of the microbeads LO in the microfluidic wafer 300 as specified in the detection standard, and therefore will not be elaborated upon further.

[0083] [Other Forms of Microfluidic Processing Systems]

[0084] In some embodiments, the microfluidic processing system 1000 can be implemented as a portable miniature device, as shown in Figure 5. In these embodiments, the microfluidic processing system 1000 includes a microfluidic chip device 1001, a control device 1002, a computing device 1003, a circuit board 402, and a housing 200. The microfluidic chip device 1001 is electrically connected to the control device 1002 via the circuit board 402, and the control device 1002 communicates wirelessly with the computing device 1003. Both the control device 1002 and the circuit board 402 can be housed within the housing 200, forming a portable miniature device.

[0085] In some embodiments, the microfluidic chip device 1001 is detachably inserted into the circuit board 402. This allows the microfluidic chip device 1001 to be removed after use in a biomedical testing procedure, and another microfluidic chip device to be inserted into the circuit board 402 for another biomedical testing procedure.

[0086] In other embodiments, the microfluidic processing system of the present invention may also employ other configurations. For example, two or more microfluidic chip devices may be detachably inserted into circuit board 402, or two or more microfluidic chip devices may be detachably inserted into two or more circuit boards.

[0087] In some embodiments, the functions of the computing device 1003 and the control device 1002 shown in Figure 3 can be integrated into a single control device. Those skilled in the art will understand from the foregoing how a control device integrating the functions of the computing device 1003 and the control device 1002 operates in conjunction with the microfluidic wafer device 1001; therefore, this will not be elaborated upon.

[0088] It should be noted that certain terms in the specification and claims of this invention (including: housing, circuit board, time interval) are preceded by "first" or "second". These "first" and "second" are used to distinguish these terms from each other. Unless otherwise specified, or if the order of these terms is not apparent from the context, the order of these terms is not restricted by the prefix "first" or "second".

[0089] In summary, the microfluidic chip device provided by this invention has injection tracks on the wall of the housing's base portion, such that when the circuit board of the microfluidic chip device is embedded in the receiving area of ​​the base portion, the space on the circuit board used to accommodate microbeads for the microfluidic chip is connected to at least one injection track. Therefore, the injection device can inject microbeads into the space of the microfluidic chip used to accommodate microbeads via the injection tracks. Since the injection device can be placed on the injection tracks, the injection device is more stable, allowing the microbeads to be injected more smoothly into the space, and the microfluidic chip will not be damaged during the injection process. Furthermore, the microfluidic chip device provided by this invention can be used in conjunction with a control device to form a microfluidic processing system, or it can be used in conjunction with a control device and a computing device to form a microfluidic processing system. The computing device and / or the control device distinguishes the microelectrode elements of the microfluidic chip into injection control areas (adjacent to the injection tracks) and non-injection control areas, so that the microfluidic chip stabilizes the injected microbeads under the action of dielectric wetting technology. Therefore, the microfluidic wafer device and microfluidic processing system provided by the present invention can easily, stably and accurately control the volume of microbeads injected into the digital microfluidic wafer, injecting microbeads of the required volume into the microfluidic wafer device, thereby making the results of biomedical testing more accurate.

[0090] The above embodiments are illustrative of some implementations of the present invention and to explain the technical features of the present invention, and are not intended to limit the scope and range of protection of the present invention. Any changes or equivalent arrangements that can be easily made by those skilled in the art to which this invention pertains are within the scope of the present invention, and the scope of protection of the present invention is determined by the claims.

[0091] 1: Microelectrode components 11: Microfluidic Electrode 13: Multifunctional Electrode 15: Control Circuit 20: Microelectrode interface 22, 24: Hydrophobic layer 100, 100', 100'': Shell 101: Seat 101B: Base 101R, 101L, 101W: wall 102: Cover 103, 103', 103a, 103b: Injection Tracks 106a, 106b: Injection channels 111: Storage Area 151: Microfluidic Control and Position Sensing Circuits 153: Temperature and Magnetic Field Control Circuit 153': Temperature control circuit 155: Storage Circuit 157: Storage Circuit 200: Housing 300: Microfluidic chip 301: Top Plate 302: Microelectrode array 303: Conductive foam 401: Circuit Board 401a: Part of a circuit board 402: Circuit Board 1000: Microfluidic Processing System 1001, 1001', 1001'': Microfluidic wafer devices 1002: Control device 1003: Computing device a1, a2: included angle C1: Capacitance value CLK1, CLK2: Clock signals CP1, CP2: Sample control patterns CA: Injection Control Area DI, DI1, DI2: Input signals DO, DO1, DO2: Output signals EN_S: Position sensing signal EN_F: Sample control signal EN_T: Heating control signal EN_M: Magnetic field control signal HL: Horizontal axis II: Line LO: Microbead NCA: Non-Injection Control Region S1: Heating control setting S2: Sample Operation Settings S3: Magnetic field control setting SP: Space T1, T2, T3, T4: Time intervals VS: Voltage signal

Claims

1. A microfluidic wafer device, comprising: a housing having at least one injection track; a circuit board; a conductive foam configured to be placed above the circuit board; and a microfluidic wafer configured to be placed above the conductive foam, and comprising: a top plate formed of a conductive material; and a microelectrode array disposed below the top plate, wherein a space is defined between the top plate and the microelectrode array; wherein... The conductive foam and the top plate extend beyond at least one side of the microelectrode array and are in contact with each other, wherein the at least one injection track is connected to the space so that at least one microbead can be injected into the space via the at least one injection track.

2. The microfluidic wafer device as claimed in claim 1, wherein the microelectrode array comprises a plurality of microelectrode elements connected in series, each microelectrode element being configured to read a corresponding sample operation setting in a first time interval, the conductive foam being configured to conduct electricity in a second time interval to give the top plate a preset voltage level, and each microelectrode element being further configured to enter a sample control state in the second time interval according to the corresponding sample operation setting.

3. The microfluidic wafer device as claimed in claim 2, wherein the microelectrode elements are divided into an injection control region and a non-injection control region, the sample operation settings read by the microelectrode elements corresponding to the injection control region are such that the microelectrode elements corresponding to the injection control region operate during the second time interval, and the sample operation settings read by the microelectrode elements corresponding to the non-injection control region are such that the microelectrode elements corresponding to the non-injection control region do not operate during the second time interval.

4. The microfluidic wafer device as claimed in claim 3, wherein the injection control region is adjacent to the at least one injection track.

5. The microfluidic wafer device as claimed in claim 1, wherein the microelectrode array includes a plurality of microelectrode elements connected in series, the microelectrode elements being configured to detect a plurality of capacitance values ​​between the top plate and the microelectrode elements one-to-one in a first time interval, and the microelectrode elements being further configured to output the capacitance values ​​one-to-one in a plurality of sub-time intervals in a second time interval.

6. A microfluidic processing system, comprising: a control device; and a microfluidic wafer device electrically connected to the control device, and comprising: a first housing having at least one injection track; a first circuit board; a conductive foam configured to be placed above the first circuit board; and a microfluidic wafer configured to be placed above the conductive foam, and comprising a top plate and a microelectrode array, wherein the top plate is formed of a conductive material, the microelectrode array is disposed below the top plate, and a space is defined between the top plate and the microelectrode array; wherein... The conductive foam and the top plate extend beyond at least one side of the microelectrode array and are in contact with each other, wherein the at least one injection track is connected to the space so that at least one microbead can be injected into the space via the at least one injection track.

7. The microfluidic processing system as claimed in claim 6, wherein the microelectrode array comprises a plurality of microelectrode elements connected in series, the control device is configured to provide a plurality of sample operation settings in a first time interval, and the microelectrode elements are configured to read the sample operation settings one-to-one in the first time interval, wherein, The conductive foam is configured to conduct electricity in a second time interval so that the top plate has a preset voltage level, and each of the microelectrode elements is further configured to enter a sample control state in the second time interval according to the corresponding sample operation setting.

8. The microfluidic processing system as claimed in claim 7, wherein the microelectrode elements are divided into an injection control region and a non-injection control region, wherein the sample operation settings read by the microelectrode elements corresponding to the injection control region cause the microelectrode elements corresponding to the injection control region to operate during a second time interval, and the sample operation settings read by the microelectrode elements corresponding to the non-injection control region cause the microelectrode elements corresponding to the non-injection control region to not operate during the second time interval.

9. The microfluidic processing system as claimed in claim 8, wherein the injection control region is adjacent to the at least one injection track.

10. The microfluidic processing system as claimed in claim 7, wherein the microelectrode elements are configured to detect a plurality of capacitance values ​​between the top plate and the microelectrode elements one-to-one in a first time interval, the microelectrode elements are further configured to output the capacitance values ​​one-to-one in a plurality of sub-time intervals in a second time interval, and the control device is configured to receive the capacitance values ​​in the second time interval.

11. The microfluidic processing system of claim 10, wherein the control device is further configured to determine a size and a position of each of the at least one microbead between the top plate and the microelectrode array based on the capacitance values.

12. The microfluidic processing system of claim 10, wherein the control device is further configured to transmit the capacitance values ​​to a computing device, such that the computing device determines a size and a position of each of the at least one microbead between the top plate and the microelectrode array based on the capacitance values.

13. The microfluidic processing system as claimed in claim 6 further comprises: a second circuit board electrically connected to the control device and the microfluidic wafer device; and a second housing configured to house the control device and the second circuit board.

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