CN110988087A - Microfluidic impedance type biological online detection device - Google Patents
Microfluidic impedance type biological online detection device Download PDFInfo
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Abstract
The invention discloses an online detection device of a microfluidic impedance type organism, which belongs to the field of biological detection, and is a portable intelligent device by effectively integrating a microfluidic chip system, an impedance detection processing system and a main equipment system, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, the detection and the result display can be realized only by injecting a detection object, and the online detection device has the advantages of high detection sensitivity, simple operation, low cost and good overall operability; the nano magnetic particles are coupled with the antibody, the biological antibody is fixed on the gold interdigital electrode under the action of the magnetic field generator, so that the biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, so that the detection sensitivity is improved; when the gold interdigital electrode does not act, the biological antibody is separated from the gold interdigital electrode, so that the cleaning of the micro-channel is facilitated, and the recycling of the micro-fluidic chip is realized.
Description
Technical Field
The invention relates to the field of biological detection, in particular to a microfluidic impedance type biological online detection device.
Background
Security incidents caused by bacterial viruses have constituted a significant threat to public health and socioeconomic development. If the publication of the Australia agriculture and forestry fisheries department in 2013 states that the concentrated mature protein powder product produced by the New Zealand constant natural group (the largest chocolate dairy product processing enterprise worldwide) may contain over-standard Escherichia coli O157: H7, the New Zealand authority immediately announces that 1000 tons of suspected pollution chocolate corresponding dairy products are recalled globally. In 8 months in 2017, the eggs are smelled by the explosion of toxic eggs in Europe, the eggs are polluted in a large range by insecticides, liver damage and thyroid gland function damage can be caused by the large-scale use of the insecticides, and nearly twenty countries in Europe are affected.
Therefore, the research on the rapid biological detection technology has great significance for preventing and effectively controlling the safety events induced by the biological bacteria and viruses. In the past decades, great efforts have been made to rapidly detect organisms, and various detection techniques and biosensors have been studied. In addition to conventional bacterial culture enumeration, there are a variety of other methods, such as nucleic acid-based (e.g., PCR, LAMP, NASBA, RPA and helinase), immunological-based (e.g., LFD, ELISA and ELFA) and biosensors (e.g., optical, electrochemical and mass spectrometry-based biosensors) for rapid detection of biological bacteria and viruses.
However, these techniques or devices are either complex to operate or expensive in instruments, and cannot realize intelligent online rapid detection, and also cannot meet the requirements of people on convenience, high efficiency, rapidness and intelligence in research and detection and life application.
Disclosure of Invention
1. Technical problem to be solved
Aiming at the problems in the prior art, the invention aims to provide the online detection device for the microfluidic impedance organisms, which effectively integrates a microfluidic chip system, an impedance detection processing system and a main equipment system into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, the detection and the result display can be realized only by injecting a detection object, and the online detection device has the advantages of high detection sensitivity, simple operation, low cost and good overall operability; the nano magnetic particles are coupled with the antibody, the biological antibody is fixed on the gold interdigital electrode under the action of the magnetic field generator, so that the biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, so that the detection sensitivity is improved; when the gold interdigital electrode does not act, the biological antibody is separated from the gold interdigital electrode, so that the cleaning of the micro-channel is facilitated, and the recycling of the micro-fluidic chip is realized.
2. Technical scheme
In order to solve the above problems, the present invention adopts the following technical solutions.
The utility model provides a biological on-line measuring device of micro-fluidic impedance formula, includes micro-fluidic chip system, impedance detection processing system and main equipment system, micro-fluidic chip system and main equipment system all are connected with impedance detection processing system, micro-fluidic chip system includes injector and micro-fluidic chip, impedance detection processing system includes impedance detection module and signal processing circuit, main equipment system includes power module, central processing unit, memory module, display module, integrated circuit and outer end interface module, micro-fluidic chip includes from last cover piece layer, channel layer and the stratum basale that down distributes once, channel layer fixed connection is between cover piece layer and stratum basale, seted up inlet and liquid outlet on the cover piece layer, include sample cistern, waste cistern, microchannel and filter membrane in the channel layer, the microchannel is located between sample cistern and the waste cistern, the micro-fluidic chip system, the impedance detection processing system and the main equipment system are effectively integrated into a portable intelligent device, so that the processes of enrichment, reaction, detection, analysis and the like can be automated, the detection and the result display can be realized only by injecting a detection object, and the detection sensitivity is high, the operation is simple, the cost is low, and the overall operability is good; the nano magnetic particles are coupled with the antibody, the biological antibody is fixed on the gold interdigital electrode under the action of the magnetic field generator, so that the biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, so that the detection sensitivity is improved; when the gold interdigital electrode does not act, the biological antibody is separated from the gold interdigital electrode, so that the cleaning of the micro-channel is facilitated, and the recycling of the micro-fluidic chip is realized.
Furthermore, the gold interdigital electrode comprises a pair of pins extending out, and the impedance detection module is connected with the gold interdigital electrode through the pins and is used for detecting an impedance signal generated by combination of a biological antibody and an antigen on the gold interdigital electrode; and the detected impedance signal is further processed by a signal processing circuit and then transmitted to the master device system.
Further, the impedance detection module comprises an AD5933 impedance detection chip.
Furthermore, the signal processing circuit comprises a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit, the amplitude of the voltage required by the A/D conversion circuit is generally 2V, and the voltage signal output by the gold interdigital electrode is relatively small, so that the voltage signal output by the gold interdigital electrode needs to be amplified, the voltage value output by the voltage amplification circuit is an analog signal, cannot be directly sent to the main equipment system for processing, and also needs to be sent to the main equipment system for result analysis after being processed by the A/D conversion circuit.
Further, the central processing unit is a programmable processor and comprises a quantitative detection model, a detection driving instruction and a threshold alarm model;
the quantitative detection model is a linear regression equation of the impedance signal Y and the concentration C of the detection object in the sample liquid, wherein Y is β C + x, β and x are constants, the concentration of the detection object is reflected through the measured impedance value, and the threshold alarm model can give out an instruction alarm when the measured concentration of the detection object exceeds a certain threshold.
Furthermore, the memory module comprises an operating system, a detection driver and a data storage, wherein the detection driver is connected with the impedance detection processing system through a port, the operating system can select an android or ios operating system to provide visual interface operation for a user, the detection driver is used for driving the AD5933 impedance detection chip to output excitation voltage with certain frequency and is used for detecting impedance signals on the gold interdigital electrode, and the impedance data of the impedance signals processed by the signal processing circuit are also stored in the memory module, so that the impedance signals can be conveniently transmitted to the central processing unit to carry out quantitative detection and threshold judgment on the concentration of a detected object.
Further, the display module includes a display screen and a speaker, the display screen can perform visualization operation, such as sending instructions, the display screen can also display the concentration of the detected object, and when the detected concentration exceeds a threshold value, the speaker 342 gives an alarm.
Furthermore, the power module is an external power adapter based on a switching power supply technology, and the output voltage of the power module is 12V and is used for supplying power to the whole device.
Furthermore, the integrated circuit comprises a voltage stabilizing circuit, a clock circuit, an IO circuit and a data register.
Furthermore, the outer end interface module is connected with other electronic equipment and is used for transmitting impedance data.
3. Advantageous effects
Compared with the prior art, the invention has the advantages that:
(1) according to the scheme, the micro-fluidic chip system, the impedance detection processing system and the main equipment system are effectively integrated into a portable intelligent device, so that the automation of the processes of enrichment, reaction, detection, analysis and the like can be realized, the detection and the result display can be realized only by injecting a detection object, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operability is good; the nano magnetic particles are coupled with the antibody, the biological antibody is fixed on the gold interdigital electrode under the action of the magnetic field generator, so that the biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by using a filter membrane, so that the detection sensitivity is improved; when the gold interdigital electrode does not act, the biological antibody is separated from the gold interdigital electrode, so that the cleaning of the micro-channel is facilitated, and the recycling of the micro-fluidic chip is realized.
(2) The gold interdigital electrode comprises a pair of pins extending out, and the impedance detection module is connected with the gold interdigital electrode through the pins and is used for detecting an impedance signal generated by combination of a biological antibody and an antigen on the gold interdigital electrode; and the detected impedance signal is further processed by a signal processing circuit and then transmitted to the master device system.
(3) The signal processing circuit comprises a voltage conversion circuit, a voltage amplification circuit and an A/D conversion circuit, the amplitude of the voltage required by the A/D conversion circuit is generally 2V, the voltage signal output by the gold interdigital electrode is relatively small, so the voltage signal output by the gold interdigital electrode needs to be amplified, the voltage value output by the voltage amplification circuit is an analog signal, the analog signal cannot be directly sent to a main equipment system for processing, and the analog signal must be sent to the main equipment system for result analysis after being processed by the A/D conversion circuit.
(4) The central processing unit is a programmable processor and comprises a quantitative detection model, a detection driving instruction and a threshold alarm model, wherein the quantitative detection model is a linear regression equation of an impedance signal Y and the concentration C of a detected object in sample liquid, Y is β C + x, β and x are constants, the concentration of the detected object is reflected through a detected impedance value, and the threshold alarm model can give an instruction alarm when the detected concentration of the detected object exceeds a certain threshold.
(5) The memory module comprises an operating system, a detection driver and a data storage, the detection driver is connected with the impedance detection processing system through a port, the operating system can select an android or ios operating system, visual interface operation is provided for a user, the detection driver is used for driving the AD5933 impedance detection chip to output excitation voltage with certain frequency and is used for detecting impedance signals on the gold interdigital electrode, impedance data of the impedance signals after being processed by the signal processing circuit are also stored in the memory module, and the impedance data are conveniently transmitted to the central processing unit to carry out quantitative detection and threshold judgment on the concentration of a detected object.
Drawings
FIG. 1 is a block diagram of the system of the present invention;
FIG. 2 is a schematic structural diagram of a microfluidic chip according to the present invention;
FIG. 3 is a flow chart of the impedance signal processing of the present invention;
FIG. 4 is a flow chart of the detection according to the present invention.
The reference numbers in the figures illustrate:
1 microfluidic chip system, 11 sample injector, 12 microfluidic chip, 2 impedance detection processing system, 21 impedance detection module, 22 signal processing circuit, 3 main equipment system, 31 power supply module, 32 central processing unit, 33 memory module, 34 display module, 35 integrated circuit, 36 outer end interface module, 4 cover sheet layer, 41 liquid inlet, 42 liquid outlet, 5 channel layer, 51 sample liquid tank, 52 waste liquid tank, 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 drawings in the embodiments of the invention will be combined; the technical scheme in the embodiment of the invention is clearly and completely described; obviously; the described embodiments are only some of the embodiments of the invention; but not all embodiments, are based on the embodiments of the invention; all other embodiments obtained by a person skilled in the art without making any inventive step; all fall within the scope of protection of the present invention.
In the description of the present invention, it should be noted that the terms "upper", "lower", "inner", "outer", "top/bottom", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplification of description, but do not indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus should not be construed as limiting the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "disposed," "sleeved/connected," "connected," and the like are to be construed broadly, e.g., "connected," which may be fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
Example 1:
referring to fig. 1, an on-line detection apparatus for micro-fluidic impedance type organisms includes a micro-fluidic chip system 1, an impedance detection processing system 2 and a main device system 3, wherein the micro-fluidic chip system 1 and the main device system 3 are both connected to the impedance detection processing system 2, the micro-fluidic chip system 1 is used as a set of detection platform for sample introduction, enrichment, capture, reaction and detection of a detected biological sample, the micro-fluidic chip system 1 includes a sample injector 11 and a micro-fluidic chip 12, and the sample injector 11 can select a micro-syringe or a pipette for introducing the detected sample liquid into the micro-fluidic chip 12 for detection.
Referring to fig. 2, the microfluidic chip 12 includes a cover sheet layer 4, a channel layer 5 and a substrate layer 6 which are distributed from top to bottom, the channel layer 5 is fixedly connected between the cover sheet layer 4 and the substrate layer 6, the cover sheet layer 4 is provided with a liquid inlet 41 and a liquid outlet 42, the channel layer 5 includes a sample liquid tank 51, a waste liquid tank 52, a microchannel 53 and a filter membrane 54, the microchannel 53 is located between the sample liquid tank 51 and the waste liquid tank 52, the microchannel 53 is in a straight shape, and the structural parameters are as follows: a liquid inlet 41 with the length of 7mm, the width of 0.5mm and the depth of 100 μm is communicated with a sample liquid groove 51, a liquid outlet 42 is communicated with a waste liquid groove 52, the sample liquid groove 51 is used for storing sample liquid before detection, the waste liquid groove 52 is used for storing waste liquid after detection, the sample liquid is guided into the sample liquid groove 51 from the liquid inlet 41 through a sample injector 11, then reaction and detection are carried out in a micro-channel 53, and then the sample liquid is discharged through the waste liquid groove 52 and the liquid outlet 42, a filter membrane 54 is fixedly connected at the connection part of the sample liquid groove 51 and the micro-channel 53, the filter membrane 54 is used for filtering larger impurity particles in the sample liquid and reducing the influence on the detection result, the upper end of a substrate layer 6 is fixedly connected with a gold interdigital electrode 61, the gold interdigital electrode 61 is positioned in the micro-channel 53, a biological antibody 62 coupled with alloy nano magnetic beads is also arranged in the micro-channel 53, the lower end of, when a magnetic field is generated, the biological antibody 62 attracting and coupling the gold nano magnetic beads is fixed on the gold interdigital electrode 61, and when the magnetic field is removed, the biological antibody 62 is separated from the gold interdigital electrode 61.
Referring to fig. 2, the gold interdigital electrode 61 includes a pair of pins 6101 extending out, and the impedance detection module 21 is connected to the gold interdigital electrode 61 through the pins 6101 for detecting an impedance signal generated by the biological antibody 62 bonded to the antigen on the gold interdigital electrode 61; and the detected impedance signal is further processed by the signal processing circuit 22 and then transmitted to the main 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, 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, a voltage amplitude required by the a/D conversion circuit is generally 2V, and a voltage signal output by the gold interdigital electrode 61 is relatively small, so that the voltage signal output by the gold interdigital electrode 61 needs to be amplified, and a voltage value output by the voltage amplification circuit is an analog signal and cannot be directly sent to the host device system 3 for processing, and further needs to be sent to the host device system 3 for result analysis after being processed by the a/D conversion circuit.
Referring to fig. 1, the main device system 3 includes a power 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 driving instruction and a threshold value alarm model;
the quantitative detection model is a linear regression equation of an impedance signal Y omega and the concentration Cmg/ml of a detection object in sample liquid, wherein Y is β C + x, β and x are constants, the concentration of the detection object is reflected through a detected impedance value, and the threshold alarm model can give out an instruction alarm when the detected concentration of the detection object exceeds a certain threshold.
The memory module 33 comprises an operating system, a detection driver and data storage, the detection driver is connected with the impedance detection processing system 2 through a port, the operating system can select an android or ios operating system, visual interface operation is provided for a user, the detection driver is used for driving the AD5933 impedance detection chip to output excitation voltage with certain frequency and is used for detecting impedance signals on the gold interdigital electrode 61, the impedance data of the impedance signals processed by the signal processing circuit 22 are also stored in the memory module 33, and the impedance signals are conveniently transmitted to the central processing unit 32 to carry out quantitative detection and threshold judgment on the concentration of a detected object.
The display module 34 includes a display screen and a speaker, the display screen can perform visual operation, for example, send instructions, the display screen can also display the concentration of the detected object, when the detected concentration exceeds a threshold value, the speaker 342 gives an alarm, the power module 31 is an external power adapter based on the switching power supply technology, the output voltage of the power module 31 is 12V for supplying power to the whole device, the integrated circuit 35 includes a voltage stabilizing circuit, a clock circuit, an IO circuit and a data register, and the external interface module 36 is connected with other electronic devices and transmits impedance data.
The invention effectively integrates the micro-fluidic chip system 1, the impedance detection processing system 2 and the main equipment system 3 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 only by injecting a detection object, the detection sensitivity is high, the operation is simple, the cost is low, and the overall operability is good; through the coupling of the nano magnetic particles with the antibody, the biological antibody 62 is fixed on the gold interdigital electrode 61 under the action of the magnetic field generator 63, so that the biological antigen can be effectively and specifically enriched and captured, and larger impurity particles are filtered by the filter membrane 54, so that the detection sensitivity is improved; when the gold interdigital electrode 61 does not act, the biological antibody 62 is separated from the gold interdigital electrode 61, so that the micro-channel 53 is convenient to clean, and the micro-fluidic chip 12 can be recycled.
The above; but are merely preferred embodiments of the invention; the scope of the invention is not limited thereto; any person skilled in the art is within the technical scope of the present disclosure; the technical scheme and the improved concept of the invention are equally replaced or changed; are intended to be covered by the scope of the present invention.
Claims (10)
1. The utility model provides a biological on-line measuring device of micro-fluidic impedance which characterized in that: including micro-fluidic chip system (1), impedance detection processing system (2) and main equipment system (3), micro-fluidic chip system (1) and main equipment system (3) all are connected with impedance detection processing system (2), micro-fluidic chip system (1) includes injector (11) and micro-fluidic chip (12), impedance detection processing system (2) includes impedance detection module (21) and signal processing circuit (22), main equipment system (3) includes power module (31), central processing unit (32), memory module (33), display module (34), integrated circuit (35) and outer end interface module (36), micro-fluidic chip (12) includes from last cover slice layer (4), channel layer (5) and stratum basale (6) down once distribute, channel layer (5) fixed connection is between cover slice layer (4) and stratum basale (6), the cover plate layer (4) is provided with a liquid inlet (41) and a liquid outlet (42), the channel layer (5) comprises a sample liquid groove (51), a waste liquid groove (52), a micro channel (53) and a filter membrane (54), the micro channel (53) is positioned between the sample liquid groove (51) and the waste liquid groove (52), the filter membrane (54) is fixedly connected to the joint of the sample liquid groove (51) and the micro channel (53), the upper end of the substrate layer (6) is fixedly connected with a gold interdigital electrode (61), the gold interdigital electrode (61) is positioned in the micro channel (53), the inside of the micro channel (53) is also provided with a biological antibody (62) coupled with alloy nano magnetic beads, 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 micro-fluidic impedance type organisms according to claim 1, wherein: the gold interdigital electrode (61) comprises a pair of pins (6101) extending out, and the impedance detection module (21) is connected with the gold interdigital electrode (61) through the pins (6101).
3. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the impedance detection module (21) comprises an AD5933 impedance detection chip.
4. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the signal processing circuit (22) includes a voltage conversion circuit, a voltage amplification circuit, and an A/D conversion circuit.
5. The on-line detection device for micro-fluidic impedance type organisms 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 driving instruction and a threshold alarm model;
the quantitative detection model is a linear regression equation of an impedance signal Y (omega) and a concentration C (mg/ml) of a detection object in a sample solution, wherein Y is β C + x, and β and x are constants.
6. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the memory module (33) includes an operating system, a detection driver and a data store, the detection driver being connected to the impedance detection processing system (2) through a port.
7. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the display module (34) includes a display screen and a speaker.
8. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the power supply module (31) is an external power adapter based on a switching power supply technology, and the output voltage of the power supply module (31) is 12V.
9. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the integrated circuit (35) comprises a voltage stabilizing circuit, a clock circuit, an IO circuit and a data register.
10. The on-line detection device for micro-fluidic impedance type organisms according to claim 1, wherein: the outer end interface module (36) is connected with other electronic equipment and transmits impedance data.
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| CN201911168695.3A CN110988087A (en) | 2019-11-25 | 2019-11-25 | Microfluidic impedance type biological online detection device |
| LU102172A LU102172B1 (en) | 2019-11-25 | 2020-11-03 | On-Line Detection Device For Microfluidic Impedance Organism |
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| CN201911168695.3A CN110988087A (en) | 2019-11-25 | 2019-11-25 | Microfluidic impedance type biological online detection device |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112058325A (en) * | 2020-07-27 | 2020-12-11 | 中国计量大学 | Ultrasonic phased array microfluidic detection device and method based on immunomagnetic bead technology |
| CN114018985A (en) * | 2021-11-03 | 2022-02-08 | 中国计量大学 | Biological virus concentration detector based on internet of things technology |
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| CN114018985A (en) * | 2021-11-03 | 2022-02-08 | 中国计量大学 | Biological virus concentration detector based on internet of things technology |
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| LU102172B1 (en) | 2021-05-11 |
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