LU102172B1 - On-Line Detection Device For Microfluidic Impedance Organism - Google Patents
On-Line Detection Device For Microfluidic Impedance Organism Download PDFInfo
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- LU102172B1 LU102172B1 LU102172A LU102172A LU102172B1 LU 102172 B1 LU102172 B1 LU 102172B1 LU 102172 A LU102172 A LU 102172A LU 102172 A LU102172 A LU 102172A LU 102172 B1 LU102172 B1 LU 102172B1
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Abstract
The present invention discloses an on-line detection device for a microfluidic impedance organism, and belongs to the field of biological detection. In the on-line detection device for a microfluidic impedance organism, a microfluidic chip system, an impedance detection processing system and a master device system are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, detection and result display can be realized by only injecting a detection substance, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operation performance is good; nano magnetic particles are coupled with antibodies, biological antibodies are fixed to gold interdigital electrodes under the action of a magnetic field generator, so that biological antigen is effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, thus the detection sensitivity is improved; when the gold interdigital electrodes do not act, the biological antibodies are separated from the gold interdigital electrodes, which facilitates the cleaning of a micro-channel and realizes the recycling of a microfluidic chip.
Description
ON-LINE DETECTION DEVICE FOR MICROFLUIDIC IMPEDANCE ORGANISM LU102172 Technical Field The present invention relates to the field of biological detection, and more particularly to an on- line detection device for a microfluidic impedance organism. Background Safety incidents caused by bacteria and viruses have posed a major threat to public health and social and economic development. For example, in 2013, the Australian Government Department of Agriculture, Fisheries and Forestry issued a statement stating that the concentrated whey protein powder products produced by the Fonterra Co-operative Group (the world's largest dairy product processing enterprise) may contain excessive Escherichia coli O157:H7, and then the New Zealand authorities immediately announced a global recall of 1,000 tons of dairy products suspected of being chemically contaminated. In early August 2017, the “poisoned eggs” scandal broke out in Europe, that is, eggs were widely contaminated by insecticides which may cause liver injury and thyroid function damage when used in large amount, and nearly 20 countries in Europe were affected.
Therefore, the study of a rapid biological detection technology is of great significance to the prevention and effective control of safety incidents induced by biological bacteria and viruses. In the past few decades, people have made great efforts in rapid detection of organisms, and researched a variety of detection technologies and biosensors. In addition to the conventional bacteria culture counting method, multiple other methods, for example, nucleic acid-based (such as PCR, LAMP, NASBA, RPA and Helicase), immunology-based (such as LFD, ELISA and ELFA) biosensors (such as optical, electrochemical and mass spectrometry-based biosensors) are used for rapid detection of biological bacteria and viruses.
However, these technologies or devices are either complicated in operation or expensive in instrument, cannot realize intelligent on-line rapid detection, and cannot meet the requirements of people for convenience, high efficiency, rapidity and intelligence in research, detection and daily life applications.
Summary
1. Technical Problem to Be Solved In view of the problem existing in the prior art, the purpose of the present invention is to provide an on-line detection device for a microfluidic impedance organism, in which a microfluidic chip system, an impedance detection processing system and a master device system are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, detection and result display can be realized by only injecting a detection substance, the detection sensitivity is high, 1 the operation is simple, the cost is low, and the overall operation performance is good; nano magnetic particles are coupled with antibodies, biological antibodies are fixed to gold interdigitar 02172 electrodes under the action of a magnetic field generator, so that biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, thus the detection sensitivity is improved; when the gold interdigital electrodes do not act, the biological antibodies are separated from the gold interdigital electrodes, which facilitates the cleaning of a micro-channel and realizes the recycling of a microfluidic chip.
2. Technical Solution To solve the above problem, the present invention adopts the following technical solution: An on-line detection device for a microfluidic impedance organism, comprising a microfluidic chip system, an impedance detection processing system and a master device system, wherein the microfluidic chip system and the master device system are both connected to the impedance detection processing system, the microfluidic chip system includes a sample injector and a microfluidic chip, the impedance detection processing system includes an impedance detection module and a signal processing circuit, the master device system includes a power source module, a central processing unit, a memory module, a display module, an integrated circuit and an external interface module, the microfluidic chip includes a cover layer, a channel layer and a substrate layer which are distributed from top to bottom in sequence, wherein the channel layer is fixedly connected between the cover layer and the substrate layer, and the cover layer is provided with a solution inlet and a solution outlet; the channel layer includes a sample solution groove, a waste solution groove, a micro-channel and a filter membrane, wherein the micro-channel is located between the sample solution groove and the waste solution groove, the filter membrane is fixedly connected to the joint between the sample solution groove and the micro-channel , the upper end of the substrate layer is fixedly connected with gold interdigital electrodes, the gold interdigital electrodes are located in the micro-channel , biological antibodies coupled with gold nano magnetic beads are also provided in the micro-channel , and the lower end of the substrate layer is fixedly connected with a magnetic field generator. In the present invention, the microfluidic chip system, the impedance detection processing system and the master device system are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, detection and result display can be realized by only injecting a detection substance, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operation performance is good; nano magnetic particles are coupled with antibodies, biological antibodies are fixed to gold interdigital electrodes under the action of the magnetic field generator, so that biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using the filter membrane, thus the detection sensitivity is improved; when the gold interdigital electrodes do not act, the biological 2 antibodies are separated from the gold interdigital electrodes, which facilitates the cleaning of the micro-channel and realizes the recycling of the microfluidic chip. LU102172 Further, the gold interdigital electrode comprises a pair of pins which stretch out, wherein the impedance detection module is connected to the gold interdigital electrode by the pins, and is used to detect an impedance signal generated by the binding of a biological antibody and antigen on the gold interdigital electrode; and the detected impedance signal is further processed by the signal processing circuit, and then is transmitted to the master device system.
Further, the impedance detection module comprises an AD5933 impedance detection chip.
Further, the signal processing circuit comprises a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit, wherein the voltage amplitude required by the A/D conversion circuit is 2V in general, and the voltage signal output by the gold interdigital electrode is relatively small, so there is a need to amplify the voltage signal output by the gold interdigital electrode. The voltage value output by the voltage amplification circuit is an analog signal, which cannot be directly sent to the master device system for processing, but must be processed by the A/D conversion circuit and then sent to the master device system for result analysis.
Further, the central processing unit is a programmable processor, and the central processing unit comprises a quantitative detection model, a detection drive instruction and a threshold alarm model, wherein the quantitative detection model is a linear regression equation of an impedance signal Y and a concentration C of a detection substance in the sample solution: Y=BC+x, where B and x are constants. The concentration of the detection substance is reflected through the measured impedance value, so the threshold alarm model may issue an instruction alarm when the measured concentration of the detection substance exceeds a certain threshold.
Further, the memory module comprises an operating system, a detection driver and a data storage, wherein the detection driver is connected to the impedance detection processing system through a port. The operating system may be an Android or ios operating system, which provides users with visual interface operations. The detection driver is used to drive the AD5933 impedance detection chip to output excitation voltage at a certain frequency, and is used to detect an impedance signal on the gold interdigital electrode. The impedance data after the impedance signal is processed by the signal processing circuit is also stored in the memory module, which is convenient to be transferred to the central processing unit for quantitative detection of the concentration of the detection substance and threshold judgment.
Further, the display module comprises a display screen and a loudspeaker, wherein the display screen can perform visual operations, such as sending instructions, and the display screen can also display the concentration of the detection substance. When the detection concentration exceeds a threshold, the loudspeaker 342 gives an alarm.
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Further, the power source module is an external power adapter based on the switch mode power supply technology, and the power source module has an output voltage of 12V, and 3 102172 used to supply power to the whole device.
Further, the integrated circuit comprises a voltage stabilizing circuit, a clock circuit, an 10 circuit and a data register.
Further, the external interface module is connected to other electronic devices and transmits impedance data.
3. Beneficial Effects Compared with the prior art, the present invention has the advantages that: (1) In this solution, a microfluidic chip system, an impedance detection processing system and a master device system are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, detection and result display can be realized by only injecting a detection substance, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operation performance is good; nano magnetic particles are coupled with antibodies, biological antibodies are fixed to gold interdigital electrodes under the action of a magnetic field generator, so that biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, thus the detection sensitivity is improved; when the gold interdigital electrodes do not act, the biological antibodies are separated from the gold interdigital electrodes, which facilitates the cleaning of a micro-channel and realizes the recycling of a microfluidic chip.
(2) The gold interdigital electrode comprises a pair of pins which stretch out, wherein the impedance detection module is connected to the gold interdigital electrode by the pins, and is used to detect an impedance signal generated by the binding of the biological antibody and antigen on the gold interdigital electrode; the detected impedance signal is further processed by the signal processing circuit, and then is transmitted to the master device system.
(8) The signal processing circuit comprises a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit, wherein the voltage amplitude required by the A/D conversion circuit is 2V in general, and the voltage signal output by the gold interdigital electrode is relatively small, so there is a need to amplify the voltage signal output by the gold interdigital electrode. The voltage value output by the voltage amplification circuit is an analog signal, which cannot be directly sent to the master device system for processing, but must be processed by the A/D conversion circuit and then sent to the master device system for result analysis.
(4) The central processing unit is a programmable processor, and the central processing unit comprises a quantitative detection model, a detection drive instruction and a threshold alarm model, wherein the quantitative detection model is a linear regression equation of an impedance signal Y and a concentration C of a detection substance in the sample solution: 4
Y=BC+x, where B and x are constants. The concentration of the detection substance is reflected through the measured impedance value, so the threshold alarm model may issue an instruction | 02172 alarm when the measured concentration of the detection substance exceeds a certain threshold.
(5) The memory module comprises an operating system, a detection driver and a data storage, wherein the detection driver is connected to the impedance detection processing system through a port. The operating system may be an Android or ios operating system, which provides users with visual interface operations. The detection driver is used to drive the AD5933 impedance detection chip to output excitation voltage at a certain frequency, and is used to detect an impedance signal on the gold interdigital electrode. The impedance data after the impedance signal is processed by the signal processing circuit is also stored in the memory module, which is convenient to be transferred to the central processing unit for quantitative detection of the concentration of the detection substance and threshold judgment.
Description of Drawings Fig. 1 is a block diagram of the system of the present invention; Fig. 2 is a structural schematic diagram of the microfluidic chip of the present invention; Fig. 3 is a flow chart showing processing of the impedance signal of the present invention; and Fig. 4 is a flow chart showing detection of the present invention.
In the figures, the reference numerals are as follows:
1. microfluidic chip system; 11. sample injector; 12. microfluidic chip; 2. impedance detection processing system; 21. impedance detection module; 22. signal processing circuit; 3. master device system; 31. power source module; 32. central processing unit; 33. memory module; 34. display module; 35. integrated circuit; 36. external interface module; 4. cover layer;
441. solution inlet ; 42. solution outlet; 5. channel layer; 51. sample solution groove; 52. waste solution groove; 53. micro-channel ; 54. filter membrane; 6. substrate layer; 61. gold interdigital electrode; 6101. pin; 62. biological antibody; 63. magnetic field generator.
Detailed Description The technical solution in the embodiments of the present invention will be clearly and fully described below in combination with the drawings in the embodiments of the present invention. Apparently, the described embodiments are merely part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those ordinary skilled in the art without contributing creative labor will belong to the protection scope of the present invention.
It should be noted in the description of the present invention that terms such as "upper", "lower", "inner", "outer", "top/bottom”, etc. indicate direction or position relationships shown based on the drawings, and are only intended to facilitate the description of the present 5 invention and the simplification of the description rather than to indicate or imply that the indicated device or element must have a specific direction or constructed and operated in > 102172 specific direction, and therefore, shall not be understood as a limitation to the present invention. In addition, the terms such as "first" and "second" are only used for the purpose of description, rather than being understood to indicate or imply relative importance.
It should be noted in the description of the present invention that, unless otherwise specifically regulated and defined, terms such as "installation," "provided with", "sleeved with", "connection", etc. shall be understood in broad sense. For example, "connection" may refer to fixed connection or detachable connection or integral connection, may refer to mechanical connection or electrical connection, and may refer to direct connection or indirect connection through an intermediate medium or inner communication of two elements. For those ordinary skilled in the art, the specific meanings of the above terms in the present invention may be understood according to specific conditions.
Embodiment 1 Referring to Fig. 1, an on-line detection device for a microfluidic impedance organism, comprising a microfluidic chip system 1, an impedance detection processing system 2 and a master device system 3, wherein the microfluidic chip system 1 and the master device system 3 are both connected to the impedance detection processing system 2. As a set of detection platform, the microfluidic chip system 1 is used for sample introduction, enrichment, capture, reaction and detection of detected biological samples. The microfluidic chip system 1 includes a sample injector 11 and a microfluidic chip 12, wherein the sample injector 11 may be a micro injector or pipettor, which is used to introduce the detected sample solution into the microfluidic chip 12 for detection.
Referring to Fig. 2, the microfluidic chip 12 includes a cover layer 4, a channel layer 5 and a substrate layer 6 which are distributed from top to bottom in sequence, wherein the channel layer 5 is fixedly connected between the cover layer 4 and the substrate layer 6, and the cover layer 4 is provided with a solution inlet 41 and a solution outlet 42; the channel layer 5 includes a sample solution groove 51, a waste solution groove 52, a micro-channel 53 and a filter membrane 54, wherein the micro-channel 53 is located between the sample solution groove 51 and the waste solution groove 52, and the micro-channel 53 is in the shape like the Chinese character one and has the structural parameters of: 7mm in length, and 0.5mm in width, 100 um in depth; the solution inlet 41 is in communication with the sample solution groove 51, the solution outlet 42 is in communication with the waste solution groove 52; the sample solution groove 51 is used to store sample solution before detection, the waste solution groove 52 is used to store waste solution after detection; the sample solution is introduced into the sample solution groove 51 from the solution inlet 41 by the sample injector 11, then is reacted and detected in the micro-channel 53, and then is discharged through the waste solution groove 52 and the solution outlet 42; the filter membrane 54 is fixedly connected to the joint between the 6 sample solution groove 51 and the micro-channel 53, the filter membrane 54 is used to filter large impurity particles in the sample solution, to reduce influence on the detection results; the 102172 upper end of the substrate layer 6 is fixedly connected with gold interdigital electrodes 61, the gold interdigital electrodes 61 are located in the micro-channel 53, biological antibodies 62 coupled with gold nano magnetic beads are also provided in the micro-channel 53, and the lower end of the substrate layer 6 is fixedly connected with a magnetic field generator 63, the magnetic field generator 63 including an electromagnetic coil, which makes the biological antibodies 62 coupled with gold nano magnetic beads be engaged and fixed to the gold interdigital electrodes 61 when a magnetic field is generated, and makes the biological antibodies 62 be disengaged from the gold interdigital electrodes 61 when the magnetic field is removed.
Referring to Fig. 2, the gold interdigital electrode 61 comprises a pair of pins 6101 which stretch out, wherein the impedance detection module 21 is connected to the gold interdigital electrode 61 by the pins 6101, and is used to detect an impedance signal generated by the binding of the biological antibody 62 and antigen on the gold interdigital electrode 61; and the detected impedance signal is further processed by the signal processing circuit 22, and then is transmitted to the master device system 3.
Referring to Fig. 1, the impedance detection processing system 2 includes an impedance detection module 21 and a signal processing circuit 22, wherein the impedance detection module 21 includes an AD5933 impedance detection chip; and the signal processing circuit 22 includes a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit. Referring to Fig. 3, the voltage amplitude required by the A/D conversion circuit is 2V in general, and the voltage signal output by the gold interdigital electrode 61 is relatively small, so there is a need to amplify the voltage signal output by the gold interdigital electrode 61. The voltage value output by the voltage amplification circuit is an analog signal, which cannot be directly sent to the master device system 3 for processing, but must be processed by the A/D conversion circuit and then sent to the master device system 3 for result analysis.
Referring to Fig. 1, the master device system 3 includes a power source module 31, a central processing unit 32, a memory module 33, a display module 34, an integrated circuit 35 and an external interface module 36.
The central processing unit 32 is a programmable processor, and the central processing unit 32 comprises a quantitative detection model, a detection drive instruction and a threshold alarm model, wherein the quantitative detection model is a linear regression equation of an impedance signal Y Q and a concentration C mg/ml of a detection substance in the sample solution: Y=BC+x, where B and x are constants. The concentration of the detection substance is reflected through the measured impedance value, so the threshold alarm model may issue an instruction 7 alarm when the measured concentration of the detection substance exceeds a certain threshold. LUt02172 The memory module 33 comprises an operating system, a detection driver and a data storage, wherein the detection driver is connected to the impedance detection processing system 2 through a port. The operating system may be an Android or ios operating system, which provides users with visual interface operations. The detection driver is used to drive the AD5933 impedance detection chip to output excitation voltage at a certain frequency, and is used to detect an impedance signal on the gold interdigital electrode 61. The impedance data after the impedance signal is processed by the signal processing circuit 22 is also stored in the memory module 33, which is convenient to be transferred to the central processing unit 32 for quantitative detection of the concentration of the detection substance and threshold judgment.
The display module 34 includes a display screen and a loudspeaker, wherein the display screen can perform visual operations, such as sending instructions, and the display screen can also display the concentration of the detection substance. When the detection concentration exceeds a threshold, the loudspeaker 342 gives an alarm. The power source module 31 is an external power adapter based on the switch mode power supply technology, and the power source module 31 has an output voltage of 12V, and is used to supply power to the whole device. The integrated circuit 35 comprises a voltage stabilizing circuit, a clock circuit, an 10 circuit and a data register. The external interface module is connected to other electronic devices and transmits impedance data.
In the present invention , the microfluidic chip system 1, the impedance detection processing system 2 and the master device system 3 are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, detection and result display can be realized by only injecting a detection substance, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operation performance is good; nano magnetic particles are coupled with antibodies, biological antibodies 62 are fixed to gold interdigital electrodes 61 under the action of the magnetic field generator 63, so that biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using the filter membrane 54, thus the detection sensitivity is improved; when the gold interdigital electrodes 61 do not act, the biological antibodies 62 are separated from the gold interdigital electrodes 61, which facilitates the cleaning of the micro-channel 53and realizes the recycling of the microfluidic chip 12.
The above only describes the specific embodiments of the present invention and the protection scope of the present invention is not limited to the above content. Any equivalent replacement or change made by those skilled in the art familiar with the technical field within the technical scope disclosed by the present invention according to the technical solution of the present invention and improve concept thereof shall be covered within the protection scope of the present invention.
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Claims (10)
1. An on-line detection device for a microfluidic impedance organism, comprising a microfluidic chip system (1), an impedance detection processing system (2) and a master device system (3), wherein the microfluidic chip system (1) and the master device system (3) are both connected to the impedance detection processing system (2); the microfluidic chip system (1) includes a sample injector (11) and a microfluidic chip (12), the impedance detection processing system (2) includes an impedance detection module (21) and a signal processing circuit (22), the master device system (3) includes a power source module (31), a central processing unit (32), a memory module (33), a display module (34), an integrated circuit (35) and an external interface module (36), the microfluidic chip (12) includes a cover layer (4), a channel layer (5) and a substrate layer (6) which are distributed from top to bottom in sequence, wherein the channel layer (5) is fixedly connected between the cover layer (4) and the substrate layer (6), and the cover layer (4) is provided with a solution inlet (41) and a solution outlet (42); the channel layer (5) includes a sample solution groove (51), a waste solution groove (52), a micro-channel (53) and a filter membrane (54), wherein the micro-channel (53) is located between the sample solution groove (51) and the waste solution groove (52), the filter membrane (54) is fixedly connected to the joint between the sample solution groove (51) and the micro-channel (53), the upper end of the substrate layer (6) is fixedly connected with gold interdigital electrodes (61), the gold interdigital electrodes (61) are located in the micro-channel (53), biological antibodies (62) coupled with gold nano magnetic beads are also provided in the micro-channel (53), and the lower end of the substrate layer (6) is fixedly connected with a magnetic field generator (63).
2. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the gold interdigital electrode (61) comprises a pair of pins (6101) which stretch out, wherein the impedance detection module (21) is connected to the gold interdigital electrode (61) by the pins (6101).
3. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the impedance detection module (21) comprises an AD5933 impedance detection chip.
4. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the signal processing circuit (22) comprises a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit.
5. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the central processing unit (32) is a programmable processor, and the central processing unit (32) comprises a quantitative detection model, a detection drive instruction and — athreshold alarm model, 9 wherein the quantitative detection model is a linear regression equation of an impedance signal Y (Q) and a concentration C (mg/ml) of a detection substance in the sample solutioh” 192172 Y=BC+x, where B and x are constants.
6. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the memory module (33) comprises an operating system, a detection driver and a data storage, wherein the detection driver is connected to the impedance detection processing system (2) through a port.
7. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the display module (34) comprises a display screen and a loudspeaker.
8. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the power source module (31) is an external power adapter based on the switch mode power supply technology, and the power source module (31) has an output voltage of 12V.
9. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the integrated circuit (35) comprises a voltage stabilizing circuit, a clock circuit, an 10 circuit and a data register.
10. The on-line detection device for a microfluidic impedance organism according to claim 1, wherein the external interface module (36) is connected to other electronic devices and transmits impedance data.
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