CN117309709A - Exhaled gas marker detection method and device based on suspended particles - Google Patents
Exhaled gas marker detection method and device based on suspended particles Download PDFInfo
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Abstract
The invention discloses an exhaled gas marker detection method and device based on suspended particles, which are used for carrying out functional modification on the surfaces of the suspended particles so that target substances to be detected can be specifically combined to the surfaces of the suspended particles to generate quality change. And calculating the mass of the particles according to the displacement power spectral density signal of the suspended particles in the alternating electric field and the displacement power spectral density signal under the action of the electric charge quantity carried by the particles and the thermal noise. The invention can realize the quality detection capability of fg magnitude by means of the high-sensitivity mechanical detection performance of the suspended particles, and the marker detection capability reaches hundreds of molecular levels. By modifying the corresponding specific binding substances on the surfaces of the particles and matching with the corresponding gas path design, the quality change of the gas to be detected before and after the gas to be detected is introduced is compared, and the in-situ trace detection of the specific markers in the exhaled gas can be realized.
Description
Technical Field
The invention relates to the crossing field of aerosol detection and gas marker detection, in particular to an exhaled gas marker detection method and device based on aerosol.
Background
Screening and diagnosis of various diseases by disease biomarkers contained in exhaled breath has become a research hotspot in recent years. The exhaled breath of humans contains a number of volatile organic compounds (Volatile Organic Compounds, VOCs), which, according to the World Health Organization (WHO) definition, refer to various organic compounds having a boiling point of 50 ℃ to 260 ℃ at normal temperature. Generally, non-methane hydrocarbons (NMHCs), oxygen-containing organic compounds, halogenated hydrocarbons, nitrogen-containing organic compounds, sulfur-containing organic compounds, and the like are classified into several general classes. While the non-volatile molecules contained in exhaled air are predominantly present in the form of small droplets, which are believed to originate from the airway lining fluid of the lungs. When the temperature decreases, it condenses into an exhaled gas condensate (Exhaled Breath Condensate, EBC). Since many markers in EBC are derived directly from the lungs, it is easier to obtain information about the lungs relative to saliva. Currently, there have been studies to demonstrate that various lung cancer markers such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC) in blood can be detected in EBC, and that CEA concentration in EBC has a more diagnostic value for early lung cancer than in blood. Thus, detection of disease markers in exhaled breath has great potential in the noninvasive screening of early stage pulmonary disease.
Compared with other body fluid detection such as blood, urine, sweat and the like, the expiration detection is more and more important because of the advantages of safety, noninvasive property, convenience and the like. The traditional gas analysis method has the combination of gas chromatography-mass spectrometry (gas chromatography-mass spectrometry, GC-MS), is a quantitative analysis method, has extremely low detection limit, but is expensive in equipment and time-consuming in detection. Another device commonly used in the biomedical detection field is the electronic nose (electronic nose), which uses a gas sensor in combination with a detection circuit to give a qualitative or semi-quantitative result. However, the gas sensor used in the traditional electronic nose generally has a broad-spectrum response, and a sensor array is required to be formed and matched with a specific algorithm to obtain a result, so that the detection limit is poor; in addition, the commonly used MOS (Metal-Oxide-Semiconductor Field-Effect Transistor, MOSFET, abbreviated as MOS) sensor is sensitive to temperature, and needs to be preheated to hundreds of degrees centigrade when in use, so that detection can be performed, and the time is relatively long.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides an exhaled gas marker detection method and device based on suspended particles, which can improve the detection limit of markers in gas and achieve the aim of trace and rapid exhaled gas detection.
The aim of the invention is achieved by the following technical scheme:
a method of detecting exhaled breath markers based on aerosols, the method comprising the steps of:
step one: carrying out surface functionalization modification on the particles according to the target substance to be detected;
step two: capturing particles and suspending the particles in a vacuum cavity, wherein the vacuum degree in the vacuum cavity needs to meet the heat balance condition;
step three: applying a magnitude E to the suspended particles 0 Frequency omega dr The simple harmonic alternating current electric field of (2) to obtain suspended particles at a frequency omega dr Amplitude S of the displacement power spectral density response at x (ω dr ) The method comprises the steps of carrying out a first treatment on the surface of the The size of the simple harmonic alternating current electric field ensures that the motion range of the suspended particles under the action of the electric field is in the optical trap linear region;
step four: closing the electric field, under the action of thermal noise, obtaining suspended particles at a frequency omega dr Amplitude S of the displacement power spectral density response at th (ω dr ) And calculates a damping rate Γ at the vacuum level 0 ；
Step five: measuring the number N of charges carried by suspended particles q ；
Step six: calculating mass m of suspended particles 0 ；
Step seven: will beRestoring normal pressure in the vacuum cavity, introducing the gas to be detected into the position where the suspended particles are located, restoring the vacuum degree to the level in the second step, and repeating the third to sixth steps to obtain the mass m of the suspended particles at the moment 1 ；
Step eight: according to the mass change of the suspended particles before and after the gas to be detected is introduced, the mass of the target substance in the exhaled gas is rapidly and trace in-situ detected.
Further, in the second step, the vacuum degree meeting the heat balance condition is 10 mbar-50 mbar, and the mass center motion equivalent temperature of the suspended particles is the ambient temperature.
Further, the suspended particles obtained in step three and step four are at a frequency ω dr Amplitude S of the displacement power spectral density response at x (ω dr ) And S is th (ω dr ) Is obtained by demodulating continuous response amplitude values through a phase-locked loop and taking an average value.
Further, in the fourth step, the damping rate Γ 0 Is obtained by Lorentz fitting the displacement power spectrum density of the suspended particles.
Further, in the sixth and seventh steps, the calculation formula of the mass of the suspended particles is as follows:
wherein q e Is the meta-charge, τ is the sampling time, k B Is Boltzmann constant, T is temperature, R s =[S x (ω dr )-S th (ω dr )]/S th (ω dr ) Is the ratio of the magnitude of the power spectral density response under the action of electric field force and thermal noise.
Further, in the fifth step, the number N of charges carried by the suspended particles is measured q The method comprises the following steps:
applying a frequency omega to a pair of parallel electrodes dr To form an alternating electric field, the position of the suspended particles being within the electric field coverage; demodulation of omega dr The signal at the location obtains suspended particlesThe response amplitude of the electric field force is utilized to adjust the charge quantity of the particles through ultraviolet light excitation or high-voltage corona discharge, and the charge quantity N of the particles can be measured according to the change of the response amplitude q 。
Further, the particles in the first step are standard optical uniform medium spheres with known mass, the shape is spherical, the size is hundred nanometers, and the material is silicon dioxide or gold.
Further, the substance for performing surface functionalization modification on the microparticles in the first step includes antigen, antibody, enzyme, single-stranded DNA and single-stranded RNA.
Further, the manner of capturing and suspending the particles in the second step is optical suspension, magnetic suspension or electric suspension.
An exhaled air marker detection device based on suspended particles is used for realizing an exhaled air marker detection method based on the suspended particles; the device comprises a vacuum cavity particle suspension and detection unit and a detection gas loading unit;
the vacuum cavity particle suspension and detection unit comprises a high-voltage direct-current power supply, a bare wire electrode, a vacuum cavity, a capturing light laser, an objective lens, a parallel electrode, a collecting lens, a four-quadrant photoelectric detector, a lock-in amplifier, a signal generator and a power amplifier;
the capture laser emits capture laser, the capture laser is focused through the objective lens to form a capture light field, and particles are captured in the vacuum cavity; scattered light formed by the captured light field passing through the particles is emitted to a detection unit through the collection lens, collected by the four-quadrant photoelectric detector, and transmitted to the phase-locked amplifier for collection and analysis; the signal generator is used for generating a resonance signal with specific frequency, and the resonance signal is loaded on the parallel electrodes through the power amplifier to form a simple harmonic electric field on one hand, and is synchronously input into the lock-in amplifier as a reference signal on the other hand; the high-voltage direct-current power supply performs corona discharge in the vacuum cavity through the two bare wire electrodes, so that the regulation and control of the charge quantity carried by the particles are realized;
the detection gas loading unit comprises a drying pipe, a filter plug, a third electromagnetic valve, a fourth electromagnetic valve, a metering ring, a first electromagnetic valve, a first air pump, a second electromagnetic valve and a detection gas circuit; the electromagnetic valve III and the electromagnetic valve IV are two-position three-way electromagnetic valves, a first interface of the electromagnetic valve III is connected with the filter plug, the filter plug is connected with the drying pipe, a second interface of the electromagnetic valve III is connected with one end of the detection gas circuit, and the other end of the detection gas circuit is inserted into a particle suspension position in the vacuum cavity; the interface III of the electromagnetic valve III is connected with one end of the metering ring; the first connector of the electromagnetic valve is connected with the other end of the metering ring, the second connector is communicated with the air pump I through a pipeline, and the third connector is connected with the air pump II through a pipeline; the electromagnetic valve I is arranged on a pipeline which is communicated with the air pump I through a connector II of the electromagnetic valve IV, and the electromagnetic valve II is arranged on a pipeline which is communicated with the air pump II through a connector III of the electromagnetic valve IV.
The beneficial effects of the invention are as follows:
the invention provides a method and a device for highly sensitive, in-situ, rapid and trace detection of exhaled gas markers through functionalized modified suspended particles. After the surface of the suspended particles is functionally modified, an alternating electric field is applied to the suspended particles, and a displacement power spectrum of the suspended particles is obtained. The mass of the suspended particles can be calculated by combining displacement power spectrum data when no electric field is applied. The quality detection capability of fg magnitude can be realized by means of the high-sensitivity mechanical detection performance of the suspended particles, and the marker detection capability reaches hundreds of molecular levels. Because the size and the mass of the suspended particles are small and sensitive to mass change, the ultra-low detection limit of the target substance can be realized. In order to measure the mass of the suspended particles more accurately, the invention adopts an electric field force-thermal noise response ratio calibration method to obtain a smaller measurement error than that of the traditional power spectrum density fitting method. In addition, the method of the invention detects the quality change, and can compare the quality change before and after the gas to be detected is introduced to realize the rapid screening of the target substances, so the method can be widely applied to the in-situ and rapid trace detection of various target substances.
Drawings
Fig. 1 is a schematic diagram of an aerosol-based exhaled breath marker detection method according to an embodiment of the present invention.
FIG. 2 is a schematic illustration of a particle surface functionalization modification process.
FIG. 3 is a graph showing the shift Power Spectral Density (PSD) response of particles under the action of electric field force and thermal noise.
Fig. 4 is a schematic diagram of a measurement process of the number of charges carried by particles.
FIG. 5 is a graph showing the displacement PSD response of particles before and after introducing a test gas.
FIG. 6 is a graph showing the displacement PSD response of particles detecting different concentrations of a target substance.
FIG. 7 is a standard curve of suspended particle mass versus target substance concentration.
Fig. 8 is a schematic diagram of an aerosol-based exhaled breath marker detection device according to an embodiment of the present invention.
In the figure, a high-voltage direct current power supply 1, a bare wire electrode 2, a vacuum cavity 3, a capturing light laser 4, an objective lens 5, particles 6, a parallel electrode 7, a collecting lens 8, a four-quadrant photodetector 9, a lock-in amplifier 10, a signal generator 11, a power amplifier 12, a sample gas inlet 13, a drying tube 14, a filter plug 15, a solenoid valve three 16, a solenoid valve four 17, a metering ring 18, a solenoid valve one 19, a gas pump one 20, a gas outlet 21, a carrier gas inlet 22, a gas pump two 23, a solenoid valve two 24 and a detection gas path 25.
Detailed Description
The objects and effects of the present invention will become more apparent from the following detailed description of the preferred embodiments and the accompanying drawings, it being understood that the specific embodiments described herein are merely illustrative of the invention and not limiting thereof.
As one embodiment, as shown in fig. 1, the method for detecting an exhaled breath marker based on suspended particles of the present embodiment includes the following steps:
step one: and carrying out functional modification on the surfaces of the particles according to the target substances to be detected.
The surface-modified substance may be an antigen, an antibody, an enzyme, single-stranded DNA, single-stranded RNA, or an aptamer, depending on the type of the target marker in the gas to be measured. The particles are optical uniform medium spheres, the shapes of the particles are spherical, and the materials are silicon dioxide or gold.
Step two: and a cleaning device air path.
The device gas path cleaning step should be carried out before the microspheres are captured, and the cleaning gas is dry and clean nitrogen.
Step three: the particles in the vacuum chamber are captured and suspended by the optical trap.
Step four: vacuumizing to keep the suspended particles and the gas in the vacuum cavity in a heat balance state;
the thermal equilibrium state indicates that the vacuum degree is between 10 mbar and 50 mbar, and the resonance peak can be generated at the displacement power spectrum density of the particles, and meanwhile, the sufficient heat exchange between the particles and the surrounding air can be kept.
Step five: applying frequency omega to suspended particles by parallel electrodes dr Measuring the particle frequency omega by the simple harmonic electric field of (2) dr A shifted Power Spectral Density (PSD) response signal S x (ω dr )。ω dr Is near the resonance frequency omega of the particles 0 Nearby selection, typically ω 0 ±10kHz。
In this embodiment, the parallel electrode structure is composed of two horizontally placed steel needles, and the pitch of the steel needles is about 3 mm. One electrode is connected with the simple harmonic signal after power amplification, and the other electrode is grounded. The simple harmonic electric field can be decomposed into three orthogonal axis components that respectively produce responses on the triaxial displacement power spectral density signals of the particles. Applying a magnitude U to the parallel electrodes dr At a frequency of omega dr A simple harmonic electric field is generated at the position of the particles.
Amplitude S of aerosol displacement PSD response x (ω dr ) The measurement method of (2) is as follows:
the parallel electrodes are arranged in the x-axis direction (parallel to the polarization direction of the captured light), and the displacement PSD of the particles in the x-axis direction is driven by the electric field force and is at the frequency omega dr Where a response spike is generated (as shown in fig. 3). In order to avoid peak errors caused by insufficient FFT points, a phase-locked loop is used(PLL) demodulating ω dr The continuous response amplitude at the position is averaged to obtain the frequency omega of the particles in the x-axis direction dr Amplitude S of displacement PSD response at x (ω dr ). It should be noted that S measured here x (ω dr ) In effect, is the response resulting from the combined action of the electric field force and the thermal noise force.
Step six: closing the electric field to measure the damping rate gamma of the particles under the action of thermal noise force 0 At omega dr Amplitude S of PSD response at th (ω dr )。
Amplitude S of particle displacement PSD response under thermal noise force th (ω dr ) The measurement method of (2) is as follows: the voltage applied to the parallel electrodes is turned off, the electric field is eliminated, and the particles are acted by thermal noise force only, and the frequency omega in the x-axis direction can be measured by the method in the fifth step dr Amplitude S of displacement PSD response at th (ω dr ) The damping rate Γ can be obtained by lorentz fitting 0 。
Step seven: measuring the charge N carried by the particles q 。
The amount of charge N carried by the particles q The measurement method of (2) is as follows: first, the frequency omega is applied through the electrode dr Forms a simple harmonic electric field by the driving voltage of the (E) and then demodulates omega by a phase-locked amplifier dr The response signal at the position can obtain a step-like amplitude signal (shown in fig. 4) through a plurality of discharging processes. The minimum difference between the steps is the amplitude response caused by a single charge, from which the number N of charges obtained by the particles can be measured q 。
Step eight: calculating the mass m of the suspended particles by using the measured parameters 0 。
Method for measuring mass m of suspended particles, wherein the formula is. Wherein q is e Is the meta-charge, τ is the sampling time, k B Is Boltzmann constant, T is temperature, R s The calculation formula is R, which is the ratio of the electric field force to the power spectral density response value under the action of thermal noise s =[S x (ω dr )-S th (ω dr )]/S th (ω dr )。
Step nine: and (3) returning to normal pressure, introducing the gas to be tested into the area where the suspended particles are located, and returning the vacuum degree to the level in the third step.
The method for introducing the gas to be detected comprises the steps of firstly pumping the gas to be detected into a gas path through a gas pump, then using clean dry nitrogen as carrier gas after the gas to be detected is fully filled in a metering ring, pushing sample gas in the metering ring into the position of suspended particles, and completing detection.
Step ten: repeating the steps four to seven, and calculating to obtain the mass m of the suspended particles at the moment 1 ；
Step eleven: by variation of mass m of suspended particles 1 -m 0 And calculating to obtain the content of the target substance to be detected.
The content of the target substance to be measured, and the actual measured value is the mass. Detection using a known concentration gradient of the marker sample gas can yield a mass-concentration standard curve for the marker detection, as shown in fig. 7.
In the gas marker detection method of the embodiment, the measurement error of the mass is within 5 percent, and the femtocells (10) -18 kg) other target substance content. And different kinds of gas markers, even microorganisms, can be detected according to the species of the modified substances on the surfaces of the microspheres.
As shown in fig. 2, the modification process for the surface functionalization of the microparticles is described. For example, the target antigen detection is taken as an example, the nano-particles with good uniformity can be obtained by purchasing commercial products, and the corresponding functional groups are modified on the surfaces of the particles to be connected with antibodies corresponding to the target antigen, so that the modification of the antibodies is completed. The microsphere modified with the antibody is captured and suspended by an optical trap, the gas containing the target antigen is introduced, and the target antigen is bound by the antibody to generate mass change so as to detect the content of the target antigen in the gas to be detected.
As shown in fig. 3, the displacement PSD response of the particles is determined by the electric field force and thermal noise. Omega due to thermal noise present at all times after application of the electric field dr Amplitude atS x (ω dr ) In effect, is the combined response of the electric field force and the thermal noise force. After the electric field is turned off, only the PSD response of the thermal noise force is shown in the graph, at which ω dr Amplitude S of response at th (ω dr ) And S is connected with x (ω dr ) The difference gives a response value that is generated only by the action of the electric field force: s is S el (ω dr ) = S x (ω dr ) -S th (ω dr )。
As shown in fig. 4, the measurement of the charge number of the particles is performed. Extraction of x-axis at frequency omega using PLL dr The response signal under the simple harmonic electric field, under the condition of unchanged electric field intensity, the signal amplitude is in direct proportion to the charge quantity carried by the particles. The air in the vacuum chamber is applied with a high voltage of about 1kV by the electrode, and plasma is generated during corona discharge. Electrons and positive ions in the plasma can be separated in opposite directions under the action of a high-voltage electric field and adsorbed on the surfaces of the particles, so that the charge quantity of the particles is changed. The removal of the high voltage signal stops the corona discharge and the number of charges on the particles is stably maintained. The discharge process is performed a plurality of times, and the charge amount carried by the particles can be adjusted. The upper half of FIG. 4 shows the demodulated signal amplitude, the smallest signal step difference being the single charge q e The charge amount of the particles varies with the discharge process, and the final charge amount of the particles is 7q e . The lower part of fig. 4 shows the demodulated phase change.
As shown in fig. 5, the displacement PSD response of the particles changes significantly before and after the introduction of the gas to be measured. This is because the surface of the particles incorporates additional substances that change the density, refractive index, and dielectric constant of the particles, resulting in a change in PSD.
As shown in fig. 6, the displacement PSD response of the particles to gas samples containing different concentrations of target markers is shown. The higher the target substance content, the more the PSD resonance peak shifts to the right. The left curves are more coincident because the mass change caused by the low concentration sample is insufficient to account for the apparent PSD shift.
As shown in FIG. 7, a standard curve of the mass of the suspended particles and the concentration of the target marker was obtained by the method of this example. The curve is calculated from the displacement PSD response described in fig. 6. The mass change caused by the low concentration sample is not enough to be detected, so that the slope of the standard curve corresponding to the target marker with higher concentration is larger, and the concentration detection Limit (LOD) of the marker can be calculated according to the standard curve. For the method of the present invention, the larger the molecular weight of the target marker, the lower the detection limit that can be achieved.
As shown in fig. 8, one of structures of the aerosol-based exhaled breath marker detection device for realizing the aerosol-based exhaled breath marker detection method is: comprising the following steps: and the vacuum cavity particle suspension and detection unit and the detection gas loading unit.
The vacuum cavity particle suspension and detection unit comprises a high-voltage direct current power supply 1, a bare wire electrode 2, a vacuum cavity 3, a capturing optical laser 4, an objective lens 5, particles 6, a parallel electrode 7, a collecting lens 8, a four-quadrant photoelectric detector 9, a phase-locked amplifier 10, a signal generator 11 and a power amplifier 12. The trapping laser 4 emits trapping laser light, which is focused by the objective lens 5 to form a trapping optical field, and the particles 6 are trapped in the vacuum chamber 3. Scattered light formed by the captured light field through the particles 6 is emitted to a detection unit through a collection lens 8, collected by a four-quadrant photodetector 9, and transmitted to a lock-in amplifier 10 for collection and analysis. The signal generator 11 can generate resonance signals with different frequencies, the resonance signals are loaded on the parallel electrode 7 through the power amplifier 12 to form a simple harmonic electric field, the simple harmonic electric field is synchronously input into the phase-locked amplifier 10 as a reference signal, and the phase-locked amplifier 10 can extract signal components with the same frequency as the electric field from the input signals of the four-quadrant photoelectric detector 9. The high-voltage direct current power supply 1 performs corona discharge in the vacuum cavity 3 through the two bare wire electrodes 2, so as to realize regulation and measurement of the charge quantity carried by the particles 6.
The detection gas loading unit comprises a drying pipe 14, a filter plug 15, a third electromagnetic valve 16, a fourth electromagnetic valve 17, a metering ring 18, a first electromagnetic valve 19, a second electromagnetic valve 24, a first air pump 20, a second air pump 23 and a detection gas path 25. The electromagnetic valve III 16 and the electromagnetic valve IV 17 are two-position three-way electromagnetic valves, the first port of the electromagnetic valve III 16 is connected with the filter plug 15, and the filter plug 15 is connected with the drying pipe 14. The interface II of the electromagnetic valve III 16 is connected with one end of the detection air path 25, and the other end of the detection air path 25 is inserted into the particle suspension position in the vacuum cavity 3; the interface III of the electromagnetic valve III 16 is connected with one end of the metering ring 18; the first connector of the electromagnetic valve IV 17 is connected with the other end of the metering ring 18, the second connector is communicated with the first air pump 20 through a pipeline, and the third connector is connected with the second air pump 23 through a pipeline; the first electromagnetic valve 19 is arranged on a pipeline of the second interface of the fourth electromagnetic valve 17 communicated with the first air pump 20, and the second electromagnetic valve 24 is arranged on a pipeline of the third interface of the fourth electromagnetic valve 17 communicated with the second air pump 23.
Before capturing particles, the electromagnetic valve II 24 is in a conducting state, the electromagnetic valve III 16 and the electromagnetic valve IV 17 are in a dotted line gas path conducting state, clean dry nitrogen is used as cleaning gas, and the cleaning gas is pumped into a gas path through the air pump II 23 from the carrier gas inlet 22 until the cleaning gas completes cleaning of the detection gas path 25; the first electromagnetic valve 19 is in a conducting state, the third electromagnetic valve 16 and the fourth electromagnetic valve 17 are in a solid-line gas channel conducting state, the sample gas to be tested enters from the sample gas inlet 13 and is pumped into the gas channel through the first air pump 20, and after the metering ring 18 is completely filled, the first electromagnetic valve 19 is closed, so that sample injection of the gas to be tested is completed; the second electromagnetic valve 24 is in a conducting state, the third electromagnetic valve 16 and the fourth electromagnetic valve 17 are in a dotted line gas channel conducting state, clean dry nitrogen is used as carrier gas, the clean dry nitrogen is pumped into the gas channel from the carrier gas inlet 22 through the second air pump 23, and sample gas in the metering ring 18 is pushed into the detection gas channel 25 by the carrier gas to reach the position of suspended particles 6, so that gas detection is completed. The drying tube 14 is used for absorbing moisture in the gas to be detected, so that the quality change of suspended particles caused by the adsorption of water is avoided; the filter plug 15 is used for filtering out large particulate matters so as to avoid blocking the air pump.
A specific example is given below for a method of detecting an exhaled breath marker according to the present invention.
Example 1
Taking nano silicon dioxide particles for detecting immunoglobulin IgG as an example, the particles 6 to be captured are monodisperse silicon dioxide microsphere samples with the nominal diameter of 200 nm, and carboxyl groups and antibodies are modified for detecting the immunoglobulin IgG; the capturing optical laser 4 can adopt a 1064nm single-mode laser; setting a z-axis as an optical axis direction, and setting an x-axis as a direction parallel to light polarization; the high-voltage direct-current power supply 1 can output 1kV voltage, the bare wire electrode 2 can adopt enameled wires, and the insulating sheath at the tail end of the bare wire electrode is removed to expose the conductor part; the parallel electrode 7 consists of two horizontally placed steel needles, and the interval is 3 mm; the power amplifier 12 may output a 50 times amplified sinusoidal signal. The sample gas inlet 13 can be connected with an air bag or a blowing nozzle, the drying tube 14 is filled with active carbon and silica gel particles, and the filter plug 15 is provided with a fiber filter membrane with the pore diameter of 25 mu m. The gas path part is divided into three parts, namely a carrier gas inlet 22, a second air pump 23, a second electromagnetic valve 24 (conducting), a fourth electromagnetic valve 17 (conducting by a dotted line gas path), a metering ring 18, a third electromagnetic valve 16 (conducting by a dotted line gas path) and a detection gas path 25 to form a detection gas path; the sample gas inlet 13, the drying pipe 14, the filter plug 15, the electromagnetic valve III 16, the electromagnetic valve IV 17 (the solid gas path is conducted), the metering ring 18, the electromagnetic valve I19, the air pump I20 and the air outlet 21 form a sample gas inlet path; after the gas injection is completed, the metering ring 18 is filled with the gas to be measured, and the cleaning gas path is changed into the detection gas path.
The detection step specifically comprises the following steps:
(1) Firstly, carboxylation modification of particles is carried out by a two-step method, an amino precursor is prepared by an amino silylation reagent, and then the nano silicon dioxide with carboxylated surface is obtained by the reaction of succinic anhydride and amino on the nano silicon dioxide amino precursor. Then, amidation is performed by EDC/NHS, and the amino group on the IgG secondary antibody is connected with the carboxyl group on the surface of the particle, so that the modification of the IgG secondary antibody is completed.
(2) And cleaning the air path. As shown in fig. 8, the second solenoid valve 24 is opened, the third solenoid valve 16 and the fourth solenoid valve 17 select a dotted line gas path, clean dry nitrogen is used as cleaning gas, and the cleaning gas is pumped into the gas path from the carrier gas inlet 22 through the second air pump 23 until the cleaning gas completes cleaning of the detection gas path 25.
(3) The 1064nm capturing optical laser 4 is opened, a stable capturing optical field is formed in the vacuum cavity 3, and the surface functionalized modified silica microspheres 6 obtained in the step (1) are sent into the vacuum cavity 3 to wait for the optical field to capture suspended particles.
(4) The vacuum pump was turned on to maintain the pressure in the vacuum chamber 3 at 10 mbar.
(5) Selecting a drive frequency omega around the aerosol resonance frequency dr Obtaining a drive response S of thermal noise force according to PSD th (ω dr ) And obtaining the damping rate gamma by Lorentz fitting 0 。
(6) The signal generator 11 generates a frequency omega dr Is loaded on the parallel electrode 7 through the power amplifier 12 to form a simple harmonic electric field in the x-axis direction, and the electric field strength E can be obtained according to the amplitude of the driving signal and the distance between the parallel electrodes 7 0 Is a value of (2).
(7) Demodulation of omega under the action of simple harmonic electric field by using phase-locked amplifier 10 dr X-axis displacement PSD response signal at the position to obtain S x (ω dr )。
(8) Recording of the demodulated signal continues. The high-voltage direct-current power supply 1 is started for 1s, particles are charged at the tail end of the enameled wire through corona discharge, and the particle charge quantity can be changed by repeating the discharge process as shown in fig. 4. After the minimum step difference is determined, the final particle has an amount of charge N q = 7；
(9) The mass of the suspended particles is calculated using a formula. Before introducing the gas to be measured, S th (ω dr ) =9.95e-8 V 2 /Hz，S x (ω dr ) = 5.38e-6 V 2 /Hz，Γ 0 = 6064 Hz，N q = 7，R s =S el (ω dr )/S th (ω dr ) = [S x (ω dr )-S th (ω dr )]/S th (ω dr ) The mass of the suspended particles before the gas to be measured is introduced can be calculated。
(10) And (3) recovering the vacuum cavity 3 to normal pressure, injecting the gas to be detected (opening the first electromagnetic valve 19, opening the third electromagnetic valve 16 and the fourth electromagnetic valve 17 to select a solid line gas path, allowing the gas to be detected to enter from the sample gas inlet 13 and be pumped into the gas path through the first air pump 20, completely filling the metering ring 18, closing the first electromagnetic valve 19), then pushing the gas to be detected containing IgG into a detection position by using clean dry nitrogen as carrier gas (opening the second electromagnetic valve 24, opening the third electromagnetic valve 16 and the fourth electromagnetic valve 17 to select a dotted line gas path, allowing the carrier gas to be pumped into the gas path through the second air pump 23 from the carrier gas inlet 22, and pushing the sample gas in the metering ring 18 into the detection gas path 25), wherein the IgG is combined with the second antibody modified on the surface of the suspended particles to generate quality change.
(11) Repeating the steps (4) - (8), and introducing the gas to be tested, S th (ω dr ) =8.24e-8 V 2 /Hz，S x (ω dr ) = 6.18e-6 V 2 /Hz，Γ 0 = 6679 Hz，N q = 15，R s =S el (ω dr )/S th (ω dr ) = [S x (ω dr )-S th (ω dr )]/S th (ω dr ) The mass of suspended particles after the gas to be measured is introduced can be calculated。
(12) According to the mass difference before and after the gas to be detected is introduced, the IgG content of the gas to be detected, which is combined with the suspended particles, can be obtained to be m 1 -m 0 = 0.84 fg。
A specific example is given below for the gas marker detection Limit (LOD) of the present invention.
Example two
The detection limit of the method can be obtained by detecting a series of concentration gradient samples of the target marker and establishing a particle mass-concentration standard curve. IgG is still used as a detection marker, and sample gas of concentration gradient is prepared in an atomized manner.
The implementation steps are as follows:
(1) Surface modification of the particulate sample was performed as described in example one;
(2) Preparing solutions with IgG concentration of 0, 10,20, 50, 100, 150 and nM respectively;
(3) The atomized sample solutions were used as the gas to be measured, and were detected according to the method described in example one, and the PSD responses obtained for different sample concentrations were shown in fig. 6.
(4) From the measurement results and the sample concentration, an aerosol mass-target substance concentration standard curve is established as shown in fig. 7.
(5) According to the fitting straight line intersection point of the low concentration interval and the high concentration interval, the IgG detection limit of the method provided by the invention under the current experimental parameters is better than 30nM, and the detection performance can be further improved by optimizing the secondary antibody modified concentration.
(6) Binding IgG molecular weight and Avofiladellov constant N based on minimal detectable mass differences A The number of molecules of the target substance that can be detected by the present invention can be calculated. Taking the example of fitting the intersection of straight lines and the mass difference Deltam corresponding to the 50 nM sample, the relative molecular mass M of IgG r =160 kDa, the number of IgG molecules that can be detected by the methods and devices described herein is:。
it will be appreciated by persons skilled in the art that the foregoing description is a preferred embodiment of the invention, and is not intended to limit the invention, but rather to limit the invention to the specific embodiments described, and that modifications may be made to the technical solutions described in the foregoing embodiments, or equivalents may be substituted for elements thereof, for the purposes of those skilled in the art. Modifications, equivalents, and alternatives falling within the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (10)
1. An exhaled breath marker detection method based on suspended particles, which is characterized by comprising the following steps:
step one: carrying out surface functionalization modification on the particles according to the target substance to be detected;
step two: capturing particles and suspending the particles in a vacuum cavity, wherein the vacuum degree in the vacuum cavity needs to meet the heat balance condition;
step three: applying a magnitude E to the suspended particles 0 Frequency omega dr Is of (1)Harmonic alternating current electric field, obtaining suspended particles at frequency omega dr Amplitude S of the displacement power spectral density response at x (ω dr ) The method comprises the steps of carrying out a first treatment on the surface of the The size of the simple harmonic alternating current electric field ensures that the motion range of the suspended particles under the action of the electric field is in the optical trap linear region;
step four: closing the electric field, under the action of thermal noise, obtaining suspended particles at a frequency omega dr Amplitude S of the displacement power spectral density response at th (ω dr ) And calculates a damping rate Γ at the vacuum level 0 ；
Step five: measuring the number N of charges carried by suspended particles q ；
Step six: calculating mass m of suspended particles 0 ；
Step seven: restoring normal pressure in the vacuum cavity, introducing the gas to be detected into the position where the suspended particles are located, restoring the vacuum degree to the level in the second step, and repeating the third to sixth steps to obtain the mass m of the suspended particles at the moment 1 ；
Step eight: according to the mass change of the suspended particles before and after the gas to be detected is introduced, the mass of the target substance in the exhaled gas is rapidly and trace in-situ detected.
2. The method for detecting the exhaled breath marker based on the suspended particles according to claim 1, wherein in the second step, the vacuum degree meeting the heat balance condition is 10 mbar to 50 mbar, and the mass center motion equivalent temperature of the suspended particles is the ambient temperature.
3. The method for detecting an exhaled breath marker based on suspended particles as claimed in claim 1, wherein the suspended particles obtained in the third and fourth steps are at a frequency ω dr Amplitude S of the displacement power spectral density response at x (ω dr ) And S is th (ω dr ) Is obtained by demodulating continuous response amplitude values through a phase-locked loop and taking an average value.
4. The aerosol-based exhaled breath of claim 1The method for detecting the body marker is characterized in that in the fourth step, the damping rate Γ is 0 Is obtained by Lorentz fitting the displacement power spectrum density of the suspended particles.
5. The method for detecting an exhaled breath marker based on suspended particles as claimed in claim 1, wherein in the step six and the step seven, a calculation formula of mass of suspended particles is as follows:
；
wherein q e Is the meta-charge, τ is the sampling time, k B Is Boltzmann constant, T is temperature, R s =[S x (ω dr )-S th (ω dr )]/S th (ω dr ) Is the ratio of the magnitude of the power spectral density response under the action of electric field force and thermal noise.
6. The method for detecting an exhaled breath marker based on suspended particles as claimed in claim 1, wherein in the fifth step, the number N of charges carried by the suspended particles is measured q The method comprises the following steps:
applying a frequency omega to a pair of parallel electrodes dr To form an alternating electric field, the position of the suspended particles being within the electric field coverage; demodulation of omega dr The signal at the position obtains the response amplitude of suspended particles to the electric field force, the charge quantity of the particles is regulated by ultraviolet excitation or high-voltage corona discharge, and the charge quantity N of the particles can be measured according to the change of the response amplitude q 。
7. The method for detecting the exhaled breath marker based on the suspended particles according to claim 1, wherein the particles in the first step are standard optical uniform medium spheres with known mass, the shapes are spherical, the sizes are hundred nanometers, and the materials are silicon dioxide or gold.
8. The method for detecting an exhaled breath marker based on suspended particles as claimed in claim 1, wherein the substance for surface functionalization modification of the particles in the first step comprises antigen, antibody, enzyme, single-stranded DNA, single-stranded RNA.
9. The method for detecting an exhaled breath marker based on suspended particles as claimed in claim 1, wherein the method for capturing the particles and suspending the particles in the second step is optical suspension, magnetic suspension or electric suspension.
10. An apparatus for detecting an exhaled breath marker based on suspended particles, characterized in that the apparatus is used for realizing the method for detecting an exhaled breath marker based on suspended particles according to any one of claims 1 to 9;
the device comprises a vacuum cavity particle suspension and detection unit and a detection gas loading unit;
the vacuum cavity particle suspension and detection unit comprises a high-voltage direct-current power supply, a bare wire electrode, a vacuum cavity, a capturing light laser, an objective lens, a parallel electrode, a collecting lens, a four-quadrant photoelectric detector, a lock-in amplifier, a signal generator and a power amplifier;
the capture laser emits capture laser, the capture laser is focused through the objective lens to form a capture light field, and particles are captured in the vacuum cavity; scattered light formed by the captured light field passing through the particles is emitted to a detection unit through the collection lens, collected by the four-quadrant photoelectric detector, and transmitted to the phase-locked amplifier for collection and analysis; the signal generator is used for generating a resonance signal with specific frequency, and the resonance signal is loaded on the parallel electrodes through the power amplifier to form a simple harmonic electric field on one hand, and is synchronously input into the lock-in amplifier as a reference signal on the other hand; the high-voltage direct-current power supply performs corona discharge in the vacuum cavity through the two bare wire electrodes, so that the regulation and control of the charge quantity carried by the particles are realized;
the detection gas loading unit comprises a drying pipe, a filter plug, a third electromagnetic valve, a fourth electromagnetic valve, a metering ring, a first electromagnetic valve, a first air pump, a second electromagnetic valve and a detection gas circuit; the electromagnetic valve III and the electromagnetic valve IV are two-position three-way electromagnetic valves, a first interface of the electromagnetic valve III is connected with the filter plug, the filter plug is connected with the drying pipe, a second interface of the electromagnetic valve III is connected with one end of the detection gas circuit, and the other end of the detection gas circuit is inserted into a particle suspension position in the vacuum cavity; the interface III of the electromagnetic valve III is connected with one end of the metering ring; the first connector of the electromagnetic valve is connected with the other end of the metering ring, the second connector is communicated with the air pump I through a pipeline, and the third connector is connected with the air pump II through a pipeline; the electromagnetic valve I is arranged on a pipeline which is communicated with the air pump I through a connector II of the electromagnetic valve IV, and the electromagnetic valve II is arranged on a pipeline which is communicated with the air pump II through a connector III of the electromagnetic valve IV.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003098083A (en) * | 2001-09-25 | 2003-04-03 | Matsushita Electric Works Ltd | Suspended particle detecting device |
| CN107831099A (en) * | 2017-11-23 | 2018-03-23 | 北京是卓科技有限公司 | The detection means and detection method of air particle |
| CN108827843A (en) * | 2018-06-15 | 2018-11-16 | 华中科技大学 | The mass concentration of stationary source particulate matter and the measuring device of fineness spectrum and method |
| CN112014260A (en) * | 2020-08-08 | 2020-12-01 | 之江实验室 | Method and device for rapidly detecting microorganisms by capturing particles through optical trap |
| CN113804606A (en) * | 2021-08-26 | 2021-12-17 | 之江实验室 | Suspended light trap nanoparticle quality measurement method based on electric field calibration |
| US20230135076A1 (en) * | 2022-04-01 | 2023-05-04 | Zhejiang Lab | Method and apparatus for electric field measurement based on a levitated particle |
-
2023
- 2023-11-23 CN CN202311568293.9A patent/CN117309709A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003098083A (en) * | 2001-09-25 | 2003-04-03 | Matsushita Electric Works Ltd | Suspended particle detecting device |
| CN107831099A (en) * | 2017-11-23 | 2018-03-23 | 北京是卓科技有限公司 | The detection means and detection method of air particle |
| CN108827843A (en) * | 2018-06-15 | 2018-11-16 | 华中科技大学 | The mass concentration of stationary source particulate matter and the measuring device of fineness spectrum and method |
| CN112014260A (en) * | 2020-08-08 | 2020-12-01 | 之江实验室 | Method and device for rapidly detecting microorganisms by capturing particles through optical trap |
| CN113804606A (en) * | 2021-08-26 | 2021-12-17 | 之江实验室 | Suspended light trap nanoparticle quality measurement method based on electric field calibration |
| US20230135076A1 (en) * | 2022-04-01 | 2023-05-04 | Zhejiang Lab | Method and apparatus for electric field measurement based on a levitated particle |
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