Method and device for improving capture rate of solid conical glass pore channel single particle detection, processor and computer readable storage medium thereof

Abstract

The invention relates to a treatment method for improving the capture rate and preventing blockage in solid conical glass pore channel single particle detection. The treatment method comprises the following steps: preparing a solid conical glass pore channel; constructing a solid conical glass pore channel detection system; constructing a device for preventing blockage and increasing the capture rate; and detecting the particles and performing data analysis. The invention further relates to a device for improving the capture rate and anti-blocking processing of solid conical glass pore channel single particle detection, a processor and a computer readable storage medium thereof. According to the processing method and device for improving the capture rate and preventing blockage of single particle detection of the solid conical glass pore channel, the processor and the computer readable storage medium, complete blockage caused by particle aggregation at a pore opening is prevented through mechanical vibration of the vibrator on the electrolytic tank, and vibration can increase the driving force borne by particles; and the particle capture rate is further improved. Compared with an existing solid conical glass tube single particle detection technology, the method can remarkably prevent pore channel blockage and improve the particle capture rate.

Description

Technical Field

[0001] The present invention relates to the field of nanopore detection technology, in particular to the field of solid-state conical glass channel detection technology, and specifically refers to a processing method, device, processor and computer-readable storage medium for improving the capture rate and anti-clogging of single particle detection in solid-state conical glass channels. Background Art

[0002] Nanopore detection technology is a highly sensitive detection method based on single-molecule analysis. It detects the physical and chemical properties of target molecules by analyzing the current changes caused by molecules passing through nanopores. Its core is to use the signals generated by the interaction between nanoscale pores and molecules for detection. As an important method of nanopore detection technology, solid-state conical glass tubes have high mechanical strength, chemical stability and easy processing. They are suitable for long-term experimental detection in complex chemical environments. Compared with the nanoscale of biological nanopores, their pore size can be further expanded to the micrometer scale. At present, solid-state conical glass tubes are widely used in single-molecule detection, single-particle detection, biosensors, gene sequencing and material science.

[0003] The detection principle of the solid-state conical glass tube is that when voltage is applied at both ends of the conical glass tube, the ions in the electrolyte solution will form a stable baseline current through the orifice, and the conical structure causes the ion flow to contract at the conical end, increasing the local electric field strength of the fluid. When molecules or particles pass through the orifice, the ion flow will be partially blocked, resulting in a current change, and then a current blocking signal is obtained. This current signal can reflect the size, charge, shape and other characteristics of the molecules or particles.

[0004] The traditional solid-state conical glass tube detection of single particles is basically to enhance the electrophoretic force on the particle by applying a bias voltage, thereby driving the particle through the solid-state conical glass channel. However, when the particle size is highly close to the channel size, the particle concentration is too high or too low, and the particles themselves have different charges, the driving force on the particles will be insufficient during the detection process, and then the particles will completely block the channel, resulting in no current signal, or incomplete blockage but a decreased capture rate, which will ultimately affect subsequent experimental analysis. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of the above-mentioned prior art and to provide a processing method, device, processor and computer-readable storage medium for improving the capture rate and anti-clogging of single particle detection in solid-state conical glass channels, which meet the requirements of anti-clogging, high capture rate and a wide range of applications.

[0006] In order to achieve the above-mentioned object, the processing method, device, processor and computer-readable storage medium for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel of the present invention are as follows:

[0007] The method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging is mainly characterized in that the method comprises the following steps:

[0008] (1) Preparing a solid tapered glass channel;

[0009] (2) Construct a solid-state tapered glass channel detection system;

[0010] (3) Constructing devices to prevent clogging and increase capture rate;

[0011] (4) Detect particles and perform data analysis.

[0012] Preferably, the step (1) specifically comprises the following steps:

[0013] (1.1) removing organic impurities on the surface of the solid glass tube by piranha solution or acetone solution to obtain a clean solid glass tube;

[0014] (1.2) placing a clean solid glass tube in a P-2000 laser glass tube drawing instrument, and adjusting the panel parameters of the laser glass tube drawing instrument to obtain two sections of solid conical glass channels with the same and appropriate apertures;

[0015] (1.3) One section of the solid conical glass channel was used to observe its channel cross section using a scanning electron microscope, and the other section was used for experimental testing.

[0016] Preferably, the step (1.1) is specifically:

[0017] (1.1.1) Soak the solid glass tube in acetone solution for 24 hours to remove organic impurities on the surface of the solid glass tube;

[0018] (1.1.2) Rinse the soaked solid glass tube repeatedly with deionized water for 5 times;

[0019] (1.1.3) Dry the solid glass tube in an oven to obtain a clean solid glass tube.

[0020] Preferably, the step (2) specifically comprises the following steps:

[0021] (2.1) Prepare Ag / AgCl electrode by immersing silver wire in sodium hypochlorite solution;

[0022] (2.2) preparing an electrolyte;

[0023] (2.3) Add the particle sample to be tested into the electrolytic cell at a certain concentration and perform ultrasonic treatment before the experiment to make the sample completely dispersed in the electrolyte;

[0024] (2.4) injecting the prepared electrolyte into the interior of the solid conical glass channel, removing the bubbles in the tip of the channel, and inserting and fixing the conical end of the solid conical glass channel into the electrolytic cell;

[0025] (2.5) connecting the solid conical glass channel and the battery through the Ag / AgCl electrode;

[0026] (2.6) Place the entire device in a Faraday cage on a shock-proof table, and then connect the current amplifier to the computer via a data conversion cable.

[0027] Preferably, the step (2.1) is specifically as follows:

[0028] The silver wire was immersed in a sodium hypochlorite solution for 24 hours, taken out, rinsed repeatedly with deionized water for 3 times, and dried in an oven to obtain an Ag / AgCl electrode.

[0029] Preferably, the step (2.4) is specifically as follows:

[0030] (2.4.1) Use a microinjector to inject the prepared electrolyte into the interior of the solid conical glass channel, and remove the bubbles in the tip of the channel by standing, shaking or centrifuging to completely fill the channel with electrolyte;

[0031] (2.4.2) Insert and secure the tapered end of the solid tapered glass channel into the electrolytic cell.

[0032] Preferably, the step (2.5) is specifically as follows:

[0033] (2.5.1) Connect one end of the two Ag / AgCl electrodes to the working electrode and counter electrode of the current amplifier respectively.

[0034] (2.5.2) Insert the other end of the Ag / AgCl electrode connected to the working electrode into the solid conical glass channel, insert the other end of the Ag / AgCl electrode connected to the counter electrode into the electrolytic cell, and connect the solid conical glass channel and the battery through the Ag / AgCl electrode.

[0035] Preferably, the step (3) specifically comprises the following steps:

[0036] (3.1) Arrange a vibrator outside the electrolytic cell so that the vibrator strikes the side of the electrolytic cell;

[0037] (3.2) Control the vibration size and frequency by adjusting the vibrator position and parameter panel.

[0038] Preferably, the step (4) is specifically as follows:

[0039] (4.1) Under the experimental conditions of high sample concentration and low sample concentration, the presence or absence of applied vibration is taken as the only variable, and the initial time when the current signal becomes stable, the blockage of the current signal, and the change in the number of current signals in the same time are observed.

[0040] The device for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging is characterized in that the device comprises:

[0041] a processor configured to execute computer executable instructions;

[0042] A memory stores one or more computer executable instructions. When the computer executable instructions are executed by the processor, the various steps of the above-mentioned method for improving the capture rate of single particle detection in solid-state conical glass channels and preventing clogging are implemented.

[0043] The processor for improving the capture rate of single particle detection and anti-clogging processing in solid-state conical glass channels is characterized in that the processor is configured to execute computer-executable instructions. When the computer-executable instructions are executed by the processor, the various steps of the above-mentioned method for improving the capture rate of single particle detection and anti-clogging processing in solid-state conical glass channels are implemented.

[0044] The computer-readable storage medium is characterized in that a computer program is stored thereon, and the computer program can be executed by a processor to implement the various steps of the above-mentioned processing method for improving the capture rate of single particle detection in solid-state conical glass channels and preventing clogging.

[0045] The present invention adopts the processing method, device, processor and computer-readable storage medium for improving the capture rate and preventing blockage of single particle detection in solid-state conical glass channels, and mechanically vibrates the electrolytic cell by a vibrator to prevent particles from agglomerating at the orifice and causing complete blockage, and the vibration can increase the driving force on the particles, thereby improving the particle capture rate. Compared with the existing solid-state conical glass tube detection single particle technology, the present invention can significantly prevent channel blockage and improve the particle capture rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 The present invention is a flow chart of a processing method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging.

[0047] Figure 2 A schematic diagram of a solid-state tapered glass channel device for constructing a method for improving the capture rate of single particle detection in a solid-state tapered glass channel and preventing clogging of the present invention.

[0048] Figure 3aA schematic diagram of signals under high particle concentration and no vibration conditions for the method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging of the present invention.

[0049] Figure 3b A schematic diagram of signals under high particle concentration and vibration conditions for the method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging of the present invention.

[0050] Figure 4a A schematic diagram of signals under low particle concentration and no vibration conditions for the method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging of the present invention.

[0051] Figure 4b A schematic diagram of signals under low particle concentration and vibration conditions for the method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging of the present invention.

[0052] Figure 5 A graph showing the number of current signals with or without vibration per unit time under experimental conditions of low-concentration particle samples of the present invention for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging.

[0053] Reference numerals:

[0054] 1 Ag / AgCl electrode

[0055] 2 Solid tapered glass channel

[0056] 3 Polystyrene microspheres

[0057] 4 Electrolytic Cell

[0058] 5 Working electrode

[0059] 6 Electrode Phase

[0060] 7 Anti-vibration table

[0061] 8 Faraday Cage

[0062] 9 Current Amplifier

[0063] 10 Computer DETAILED DESCRIPTION

[0064] In order to more clearly describe the technical content of the present invention, further description is given below in conjunction with specific embodiments.

[0065] The method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging of the solid-state conical glass channel of the present invention comprises the following steps:

[0066] (1) Preparing a solid tapered glass channel;

[0067] (2) Construct a solid-state tapered glass channel detection system;

[0068] (3) Constructing devices to prevent clogging and increase capture rate;

[0069] (4) Detect particles and perform data analysis.

[0070] As a preferred embodiment of the present invention, the step (1) specifically comprises the following steps:

[0071] (1.1) removing organic impurities on the surface of the solid glass tube by piranha solution or acetone solution to obtain a clean solid glass tube;

[0072] (1.2) placing a clean solid glass tube in a P-2000 laser glass tube drawing instrument, and adjusting the panel parameters of the laser glass tube drawing instrument to obtain two sections of solid conical glass channels with the same and appropriate apertures;

[0073] (1.3) One section of the solid conical glass channel was used to observe its channel cross section using a scanning electron microscope, and the other section was used for experimental testing.

[0074] As a preferred embodiment of the present invention, the step (1.1) is specifically as follows:

[0075] (1.1.1) Soak the solid glass tube in acetone solution for 24 hours to remove organic impurities on the surface of the solid glass tube;

[0076] (1.1.2) Rinse the soaked solid glass tube repeatedly with deionized water for 5 times;

[0077] (1.1.3) Dry the solid glass tube in an oven to obtain a clean solid glass tube.

[0078] As a preferred embodiment of the present invention, the step (2) specifically comprises the following steps:

[0079] (2.1) Prepare Ag / AgCl electrode by immersing silver wire in sodium hypochlorite solution;

[0080] (2.2) preparing an electrolyte;

[0081] (2.3) Add the particle sample to be tested into the electrolytic cell at a certain concentration and perform ultrasonic treatment before the experiment to make the sample completely dispersed in the electrolyte;

[0082] (2.4) injecting the prepared electrolyte into the interior of the solid conical glass channel, removing the bubbles in the tip of the channel, and inserting and fixing the conical end of the solid conical glass channel into the electrolytic cell;

[0083] (2.5) connecting the solid conical glass channel and the battery through the Ag / AgCl electrode;

[0084] (2.6) Place the entire device in a Faraday cage on a shock-proof table, and then connect the current amplifier to the computer via a data conversion cable.

[0085] As a preferred embodiment of the present invention, the step (2.1) is specifically as follows:

[0086] The silver wire was immersed in a sodium hypochlorite solution for 24 hours, taken out, rinsed repeatedly with deionized water for 3 times, and dried in an oven to obtain an Ag / AgCl electrode.

[0087] As a preferred embodiment of the present invention, the step (2.4) is specifically as follows:

[0088] (2.4.1) Use a microinjector to inject the prepared electrolyte into the interior of the solid conical glass channel, and remove the bubbles in the tip of the channel by standing, shaking or centrifuging to completely fill the channel with electrolyte;

[0089] (2.4.2) Insert and secure the tapered end of the solid tapered glass channel into the electrolytic cell.

[0090] As a preferred embodiment of the present invention, the step (2.5) is specifically as follows:

[0091] (2.5.1) Connect one end of the two Ag / AgCl electrodes to the working electrode and counter electrode of the current amplifier respectively.

[0092] (2.5.2) Insert the other end of the Ag / AgCl electrode connected to the working electrode into the solid conical glass channel, insert the other end of the Ag / AgCl electrode connected to the counter electrode into the electrolytic cell, and connect the solid conical glass channel and the battery through the Ag / AgCl electrode.

[0093] As a preferred embodiment of the present invention, the step (3) specifically comprises the following steps:

[0094] (3.1) Arrange a vibrator outside the electrolytic cell so that the vibrator strikes the side of the electrolytic cell;

[0095] (3.2) Control the vibration size and frequency by adjusting the vibrator position and parameter panel.

[0096] As a preferred embodiment of the present invention, the step (4) is specifically as follows:

[0097] (4.1) Under the experimental conditions of high sample concentration and low sample concentration, the presence or absence of applied vibration is taken as the only variable, and the initial time when the current signal becomes stable, the blockage of the current signal, and the change in the number of current signals in the same time are observed.

[0098] The device for improving the capture rate of single particle detection and anti-blocking treatment in a solid-state conical glass channel of the present invention is characterized in that the device comprises:

[0099] a processor configured to execute computer executable instructions;

[0100] A memory stores one or more computer executable instructions. When the computer executable instructions are executed by the processor, the various steps of the above-mentioned method for improving the capture rate of single particle detection in solid-state conical glass channels and preventing clogging are implemented.

[0101] The processor for improving the capture rate of single particle detection and anti-clogging processing in solid-state conical glass channels of the present invention is characterized in that the processor is configured to execute computer-executable instructions, and when the computer-executable instructions are executed by the processor, the various steps of the above-mentioned method for improving the capture rate of single particle detection and anti-clogging processing in solid-state conical glass channels are implemented.

[0102] The computer-readable storage medium of the present invention is characterized in that a computer program is stored thereon, and the computer program can be executed by a processor to implement the various steps of the above-mentioned method for improving the capture rate of single particle detection in solid-state conical glass channels and preventing clogging.

[0103] In a specific embodiment of the present invention, a method for preventing blockage and improving capture rate when detecting single particles in a solid-state tapered glass channel is provided, the method comprising the following steps:

[0104] (1) Preparing a solid tapered glass channel;

[0105] (2) Construct a solid-state tapered glass channel detection system;

[0106] (3) Constructing devices to prevent clogging and increase capture rate;

[0107] (4) Detect particles and perform data analysis.

[0108] In the step (1), the solid conical glass channel is prepared by breaking a solid glass tube in a P-2000 laser glass tube drawing apparatus into two uniform solid conical glass channels.

[0109] The preparation method of the solid-state tapered glass channel is specifically as follows:

[0110] (1.1) Soak the solid glass tube in acetone solution or piranha solution for 24 hours to remove organic impurities on the surface of the solid glass tube, then rinse the soaked solid glass tube repeatedly with deionized water for 5 times, and finally dry the solid glass tube in an oven to obtain a clean solid glass tube;

[0111] (1.2) Place a clean solid glass tube in a P-2000 laser glass tube drawing instrument. According to the measured particle size, adjust the panel parameters of the P-2000 laser glass tube drawing instrument to prepare two sections of solid conical glass channels with suitable apertures.

[0112] (1.3) One section of the solid conical glass channel is used to observe its channel cross-section using a scanning electron microscope to ensure that the pore size is compatible with the particles to be tested, and the other section is used for experimental testing.

[0113] In the step (2), the method for constructing a solid tapered glass channel is specifically as follows:

[0114] (2.1) The silver wire is immersed in a sodium hypochlorite solution for 24 h, taken out, rinsed three times with deionized water, and dried in an oven to obtain an Ag / AgCl electrode. The Ag / AgCl electrode refers to an Ag surface coated with AgCl, i.e., an electrode obtained by immersing Ag in a NaClO solution.

[0115] (2.2) preparing an electrolyte;

[0116] (2.3) Add the particle sample to be tested into the electrolytic cell at a certain concentration and perform ultrasonic treatment before the experiment to make the sample completely dispersed in the electrolyte;

[0117] (2.4) using a microinjector to inject the prepared electrolyte into the interior of the solid conical glass channel, removing bubbles in the tip of the channel by standing / vibrating / centrifuging, etc. to completely fill the channel with the electrolyte, and then inserting and fixing the conical end of the solid conical glass channel into the electrolytic cell;

[0118] (2.5) One end of the two Ag / AgCl electrodes are connected to the working electrode and the counter electrode of the current amplifier respectively, and then the other end of the Ag / AgCl electrode connected to the working electrode is inserted into the solid conical glass channel, and the other end of the Ag / AgCl electrode connected to the counter electrode is inserted into the electrolytic cell, and the solid conical glass channel and the battery are connected through the Ag / AgCl electrode;

[0119] (2.6) Place the entire device in a Faraday cage on a shock-proof table, and then connect the current amplifier to the computer via a data conversion cable.

[0120] In the step (3), the device for preventing clogging and increasing capture rate is specifically constructed as follows:

[0121] A vibrator is arranged outside the electrolytic cell so that the vibrator's striking point touches the side of the electrolytic cell. The vibration size and frequency are controlled by adjusting the vibrator's position and parameter panel. When the vibrator vibrates the outer wall of the electrolytic cell mechanically and uniformly, the electrolyte and sample inside the electrolytic cell will also oscillate uniformly, thereby increasing the driving force on the particles and preventing the particles from agglomerating and causing blockage of the solid conical glass channel, and increasing the capture rate.

[0122] The step (4) of detecting the particle sample and performing data analysis is specifically as follows:

[0123] Under the experimental conditions of high sample concentration and low sample concentration, the presence or absence of applied vibration was used as the only variable, and Clampfit was used to observe the initial time when the current signal stabilized, the blockage of the current signal, and the change in the number of current signals in the same time.

[0124] In an embodiment of the present invention, a method for preventing blockage and improving capture rate when detecting single particles in a solid-state tapered glass channel mainly comprises the following steps:

[0125] (1) Preparation of solid conical glass channels

[0126] The solid glass tube used in this embodiment is a borosilicate solid glass tube of model BF100-78-10 produced by Sutter Instruments, Inc., USA, and has an outer diameter of 1 mm, an inner diameter of 0.78 mm, and a length of 10 cm;

[0127] Soak the solid glass tube in acetone solution for 24 hours to remove organic impurities on the surface of the solid glass tube;

[0128] After the soaked solid glass tube is repeatedly washed with deionized water for 5 times, it is placed in an oven at 85°C until it is dried to obtain a clean solid glass tube;

[0129] A clean solid glass tube is placed in a P-2000 laser glass tube drawing instrument (Sutter Instruments, Inc., USA), and the drawing instrument panel parameters are adjusted to HEAT=420, FILAMENT=4, VELCITY=25, DELAY=170, and PULL=20. According to the set parameters, the drawing instrument will first use a laser to heat the middle of the solid glass tube to a predetermined temperature to melt it, and then apply a pair of weak opposite pulling forces to both ends of the solid glass tube. The speed of the pull rod will gradually increase until it reaches the trigger point and completes the preset delay. Then, a strong hard pull is performed to break the solid glass tube, so that two sections of solid conical glass channels with the same and suitable apertures (about 6 μm in diameter) can be obtained;

[0130] One section of the solid conical glass channel was used to observe its channel cross-section through a scanning electron microscope to ensure that the pore size was compatible with the particles to be tested, and the other section was used for experimental testing.

[0131] (2) Construction of a solid-state conical glass channel detection system

[0132] Silver wires with a diameter of 0.5 mm and a length of 1 m were cut into 3 cm long each, and then the cut silver wires were placed in a sodium hypochlorite solution and soaked for 24 h, taken out, repeatedly rinsed with deionized water for 3 times, and placed in an oven for drying to obtain an Ag / AgCl electrode 1;

[0133] Prepare 4M KCl solution, and add PEG (molecular weight 6000) with a mass fraction of 10% to obtain the electrolyte used in the experiment;

[0134] Carboxyl-modified polystyrene microspheres 3 with a diameter of 5 μm were used as experimental samples. After the samples were ultrasonicated for 5 min, 0.25 μL and 0.5 μL of the microsphere stock solution (with a concentration of 50 mg / mL) were respectively added to an electrolytic cell 4 with a capacity of 0.5 mL, and the remaining capacity was added with the prepared electrolyte. The mixed sample-electrolyte was ultrasonicated for 5 min to make the sample evenly dispersed in the electrolyte.

[0135] Use a microinjector to inject 10 μL of electrolyte into the solid conical glass channel 2, and wait for the bubbles to be discharged for 5 minutes. The remaining bubbles that cannot be discharged autonomously are discharged by lightly tapping the outer surface of the solid conical glass channel with a finger, and finally the electrolyte is completely filled into the tip of the solid conical glass channel;

[0136] One end of the two Ag / AgCl electrodes are connected to the working electrode 5 and the counter electrode 6 of the current amplifier respectively, and then the other end of the Ag / AgCl electrode connected to the working electrode is inserted into the solid conical glass channel, and the other end of the Ag / AgCl electrode connected to the counter electrode is inserted into the electrolytic cell, and the solid conical glass channel and the battery are connected through the Ag / AgCl electrode;

[0137] The entire device is placed in a Faraday cage 8 on a shockproof table 7, and then the current amplifier 9 is connected to a computer 10 via a data conversion line.

[0138] (3) Constructing anti-clogging and capture rate-increasing devices

[0139] A vibrator is arranged outside the electrolytic cell, and the vibrator is adjusted to make the vibrator perform mechanical and uniform vibration on the outer wall of the electrolytic cell.

[0140] (4) Detect particles and perform data analysis

[0141] The current range was selected as 200 μA, the sampling rate was 100 kHz, and a positive voltage of 1800 mV was applied; the electrical signal was analyzed by Clampfit software.

[0142] (4.1) Experiments under high particle concentration conditions (0.5 μL)

[0143] like Figure 3a As shown, under no vibration conditions, it can be seen that the signal stabilizes after 1 minute, and the channel is completely blocked after the signal is stabilized for less than 1 minute, and no signal is generated. Reverse voltage is applied at the 5th minute, but the blockage cannot be improved, and the current baseline takes a long time to stabilize after the reverse voltage is applied.

[0144] like Figure 3b As shown, under vibration conditions, it can be seen that the signal stabilizes after 12 seconds, and no blockage occurs after the baseline stabilizes. The particles continue to pass through the hole stably and the signal continues to be generated.

[0145] Figure 3a and 3b This is a comparison chart, which aims to illustrate the stable downward signal after adding additional driving force. Among them, the downward bulge is the signal.

[0146] (4.2) Experiments with low particle concentration (0.25 μL)

[0147] like Figure 4a As shown, the recording was performed for 20 min under vibration-free conditions;

[0148] like Figure 4b As shown, the recording was performed for 20 min under vibration conditions;

[0149] Figure 4a and 4b The purpose is to illustrate that the number of downward signals generated increases significantly after adding additional driving force.

[0150] like Figure 5 As shown, the number of signals generated under the conditions of vibration and non-vibration within 5 to 15 minutes of the two experiments were counted respectively. There were 15 signals without vibration and 31 signals with vibration. In the same period of time, the number of current signals in the experiment with vibration is twice the number of current signals in the experiment without vibration.

[0151] The high concentration and low concentration experiments showed that the vibration device can effectively prevent particles from blocking the pores and effectively improve the particle capture rate.

[0152] The specific implementation scheme of this embodiment can refer to the relevant description in the above embodiment, which will not be repeated here.

[0153] It can be understood that the same or similar parts of the above embodiments can be referenced to each other, and the contents not described in detail in some embodiments can refer to the same or similar contents in other embodiments.

[0154] It should be noted that, in the description of the present invention, the terms "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance. In addition, in the description of the present invention, unless otherwise specified, the meaning of "plurality" refers to at least two.

[0155] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, segment or portion of code that includes one or more executable instructions for implementing the steps of a specific logical function or process, and the scope of the preferred embodiments of the present invention includes alternative implementations in which functions may not be performed in the order shown or discussed, including performing functions in a substantially simultaneous manner or in the reverse order depending on the functions involved, which should be understood by those skilled in the art to which the embodiments of the present invention belong.

[0156] It should be understood that the various parts of the present invention can be implemented by hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, a plurality of steps or methods can be implemented by software or firmware stored in a memory and executed by a suitable instruction execution device. For example, if implemented by hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function for a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc.

[0157] A person skilled in the art may understand that all or part of the steps in the method for implementing the above-mentioned embodiment may be completed by instructing related hardware through a program, and the corresponding program may be stored in a computer-readable storage medium, which, when executed, includes one of the steps of the method embodiment or a combination thereof.

[0158] In addition, each functional unit in each embodiment of the present invention may be integrated into a processing module, or each unit may exist physically separately, or two or more units may be integrated into one module. The above-mentioned integrated module may be implemented in the form of hardware or in the form of a software functional module. If the integrated module is implemented in the form of a software functional module and sold or used as an independent product, it may also be stored in a computer-readable storage medium.

[0159] The storage medium mentioned above can be a read-only memory, a magnetic disk or an optical disk, etc.

[0160] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0161] The present invention adopts the processing method, device, processor and computer-readable storage medium for improving the capture rate and preventing blockage of single particle detection in solid-state conical glass channels, and mechanically vibrates the electrolytic cell by a vibrator to prevent particles from agglomerating at the orifice and causing complete blockage, and the vibration can increase the driving force on the particles, thereby improving the particle capture rate. Compared with the existing solid-state conical glass tube detection single particle technology, the present invention can significantly prevent channel blockage and improve the particle capture rate.

[0162] In this specification, the present invention has been described with reference to specific embodiments thereof. However, it is apparent that various modifications and variations may be made without departing from the spirit and scope of the present invention. Therefore, the specification and drawings should be regarded as illustrative rather than restrictive.

Claims

1. A method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel, characterized in that: The method comprises the following steps: (1) Preparing a solid tapered glass channel; (2) Construct a solid-state tapered glass channel detection system; (3) Constructing devices to prevent clogging and increase capture rate; (4) Detect particles and perform data analysis.

2. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 1, characterized in that: The step (1) specifically comprises the following steps: (1.1) removing organic impurities on the surface of the solid glass tube by piranha solution or acetone solution to obtain a clean solid glass tube; (1.2) placing a clean solid glass tube in a P-2000 laser glass tube drawing instrument, and adjusting the panel parameters of the laser glass tube drawing instrument to obtain two sections of solid conical glass channels with the same and appropriate apertures; (1.3) One section of the solid conical glass channel was used to observe its channel cross section using a scanning electron microscope, and the other section was used for experimental testing.

3. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 2, characterized in that: The step (1.1) is specifically: (1.1.1) Soak the solid glass tube in acetone solution for 24 hours to remove organic impurities on the surface of the solid glass tube; (1.1.2) Rinse the soaked solid glass tube repeatedly with deionized water for 5 times; (1.1.3) Dry the solid glass tube in an oven to obtain a clean solid glass tube.

4. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 1, characterized in that: The step (2) specifically comprises the following steps: (2.1) Prepare Ag / AgCl electrode by immersing silver wire in sodium hypochlorite solution; (2.2) preparing an electrolyte; (2.3) Add the particle sample to be tested into the electrolytic cell at a certain concentration and perform ultrasonic treatment before the experiment to make the sample completely dispersed in the electrolyte; (2.4) injecting the prepared electrolyte into the interior of the solid conical glass channel, removing the bubbles in the tip of the channel, and inserting and fixing the conical end of the solid conical glass channel into the electrolytic cell; (2.5) connecting the solid conical glass channel and the battery through the Ag / AgCl electrode; (2.6) Place the entire device in a Faraday cage on a shock-proof table, and then connect the current amplifier to the computer via a data conversion cable.

5. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 4, characterized in that: The step (2.1) is specifically: The silver wire was immersed in a sodium hypochlorite solution for 24 hours, taken out, rinsed repeatedly with deionized water for 3 times, and dried in an oven to obtain an Ag / AgCl electrode.

6. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 4, characterized in that: The step (2.4) is specifically: (2.4.1) Use a microinjector to inject the prepared electrolyte into the interior of the solid conical glass channel, and remove the bubbles in the tip of the channel by standing, shaking or centrifuging to completely fill the channel with electrolyte; (2.4.2) Insert and secure the tapered end of the solid tapered glass channel into the electrolytic cell.

7. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 4, characterized in that: The step (2.5) is specifically: (2.5.1) Connect one end of the two Ag / AgCl electrodes to the working electrode and counter electrode of the current amplifier respectively. (2.5.2) Insert the other end of the Ag / AgCl electrode connected to the working electrode into the solid conical glass channel, insert the other end of the Ag / AgCl electrode connected to the counter electrode into the electrolytic cell, and connect the solid conical glass channel and the battery through the Ag / AgCl electrode.

8. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 1, characterized in that: The step (3) specifically comprises the following steps: (3.1) Arrange a vibrator outside the electrolytic cell so that the vibrator strikes the side of the electrolytic cell; (3.2) Control the vibration size and frequency by adjusting the vibrator position and parameter panel.

9. The method for improving the capture rate and preventing clogging of single particle detection in a solid-state conical glass channel according to claim 1, characterized in that: The step (4) is specifically as follows: (4.1) Under the experimental conditions of high sample concentration and low sample concentration, the presence or absence of applied vibration is taken as the only variable, and the initial time when the current signal becomes stable, the blockage of the current signal, and the change in the number of current signals in the same time are observed.

10. A device for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging, characterized in that: The device comprises: a processor configured to execute computer-executable instructions; A memory storing one or more computer executable instructions, wherein when the computer executable instructions are executed by the processor, the steps of the method for improving the capture rate of single particle detection in a solid-state conical glass channel and preventing clogging as described in any one of claims 1 to 9 are implemented.

11. A processor for improving the capture rate and anti-clogging of single particle detection in a solid-state conical glass channel, characterized in that: The processor is configured to execute computer executable instructions. When the computer executable instructions are executed by the processor, the various steps of the method for improving the capture rate and anti-clogging of single particle detection in solid-state conical glass channels described in any one of claims 1 to 9 are implemented.

12. A computer-readable storage medium, characterized in that: A computer program is stored thereon, and the computer program can be executed by a processor to implement the various steps of the method for improving the capture rate of single particle detection and anti-clogging in solid-state conical glass channels as described in any one of claims 1 to 9.

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