Analysis system and analysis method

Abstract

To provide an analytical system and an analytical method which are able to quickly and automatically capture, recognize and detect samples with a simpler device structure, obtain spectrum and mass spectrum information of sample particles, improve detection efficiency and reduce cost.SOLUTION: The analytical system includes: a fluid system where a solution containing sample particles is stored or flowing; an optical tweezer arranged towards the fluid system and configured to capture the sample particles in the fluid system; an optical detector configured to detect optical information of the sample particles in the fluid system; and a mass spectrometer arranged at a succeeding stage of the fluid system. The sample particles in the fluid system are at least partially driven by the optical tweezer toward the mass spectrometer.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to the field of analytical technology, and more particularly to an analytical system and an analytical method. [Background technology]

[0002] Optical tweezers are optical traps formed by a strongly focused laser beam. They can capture and move cells using optical gradient forces, and can even penetrate into the interior of cells to control organelles. They are widely used in cell biology research.

[0003] Research has shown that by combining optical tweezers with analytical instruments, it is possible to accurately capture cells from a solution and obtain information about the material composition, molecular structure, molecular energy levels, etc. In response to this, many researchers have proposed various analytical systems and methods based on optical tweezers.

[0004] In 2015, Yinmei Li et al. published a paper entitled "Current Research Status of Optical Tweezers Technology," which described the Raman spectrum detection of single vesicles by combining optical tweezers and Raman spectrum detection technology to capture and measure the Raman signal of single cells or vesicles using Raman optical tweezers, thereby obtaining information on the composition or structure of materials in cells. However, it was not possible to obtain information on the material composition at the molecular level.

[0005] Patent document 1 proposes a method and device for biochemically detecting and analyzing subcellular regions of single cells, combining optical tweezers technology with a mass spectrometer, capturing and separating separated cells or organelles using force generator (such as optical tweezers) technology, and transporting the separated cells and organelles via a microchannel to a sensitive detector based on optics or ionization (such as a mass spectrometer) for detection, thereby completing cell separation, packaging, transport, and detection in a single device.

[0006] Ali et al., in Non-Patent Document 1, disclosed a method for selecting and measuring a target single cell using Raman spectroscopy and mass spectroscopy sequentially, which can simultaneously provide pharmacodynamic and pharmacokinetic information of the single cell. However, in the above process, both the manipulation and transfer of the single cell require manual labor, resulting in a low level of automation. In addition, there is a risk of a mismatch between the test throughput of Raman spectroscopy and that of mass spectroscopy, which may significantly limit the test efficiency.

[0007] Although the combined analysis of single-cell spectra and mass spectra is important for biological research, drug development, tumor treatment, and other fields, there is currently no single-cell analysis instrument that can automatically detect the spectral and mass spectral information of single cells. Traditional single-cell combined spectral-mass analysis techniques are limited by the complexity of manual labor, are difficult to implement, and have low analytical efficiency, making them difficult to popularize in certain application fields. Therefore, improvements to traditional cell analysis techniques are needed to address the above-mentioned problems. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] US Patent US7767435B2 [Non-patent literature]

[0009] [Non-Patent Document 1] Ali et al., “Single-Cell Screening of Tamoxifen Abundance and Effect Using Mass Spectrometry and Raman-Spectroscopy”, Anal.Chem.,2019,91,2710 Summary of the Invention

[0010] In view of the above problems of the prior art, the technical solution of the present invention provides an analytical system and analytical method that can automatically capture, identify, and detect samples with a simpler device structure to obtain spectral and mass spectral information of sample particles, thereby improving detection efficiency and reducing costs. [Means for solving the problem]

[0011] A first aspect of the present invention provides an analysis system including a flow path system in which a solution containing sample particles is stored or flows, optical tweezers that are installed toward the flow path system and capture sample particles in the flow path system, an optical detector that detects optical information of the sample particles in the flow path system, and a mass spectrometer that is installed downstream of the flow path system, and in which sample particles are transported to the mass spectrometer in the flow path system at least partially driven by the optical tweezers. [Effects of the Invention]

[0012] According to this technical solution, optical tweezers can be used to capture and control single sample particles from a solution, and an optical detector can be used to identify and detect the optical information of the sample particles. During use, the optical tweezers can capture the sample particles while the optical detector simultaneously detects the sample particles captured by the optical tweezers and acquires their optical information. Alternatively, the optical detector can first detect the sample particles and acquire their optical information, and then the optical tweezers can capture a single sample particle from the sample particles. Finally, the optical tweezers can move the sample particles at least partially, sending the single sample particle to a mass spectrometer for detection. This analytical technique can automatically detect the optical and mass spectral information of the sample particles. Because the optical tweezers are used to capture the sample particles directly in the flow system and detect and move them in situ, there is no need to manually transport the sample particles. This eliminates the need for manual transfer of the sample particles, and the test throughput of the optical detector can be matched with that of a mass spectrometer. The process of identifying, capturing, controlling, and detecting single sample particles can be completed quickly, accurately, and automatically.

[0013] In a preferred technical solution of the present invention, the sample particles may be one or a combination of several types of cells, organelles, and single-cell microorganisms.

[0014] In a preferred technical solution of the present invention, the flow path system includes a reservoir for storing a solution and a fluid passage communicating with the reservoir, and the optical tweezers move relative to the reservoir and the fluid passage, thereby moving sample particles from the reservoir to the fluid passage at least partially by utilizing an optical gradient force.

[0015] According to this technical solution, optical tweezers are used to capture and fix a single sample particle in a reservoir. The relative movement of the optical tweezers and the fluid channel displaces the optical trap created by the optical tweezers in the fluid channel, and the sample particle fixed in the optical trap is also moved into the fluid channel under the driving force of the optical gradient force. By separately installing the reservoir and the fluid channel, it is possible to prevent unseparated and unidentified sample particles from entering the mass spectrometer along with the solution. Meanwhile, by using the optical gradient force to transport the sample particle from the reservoir to the fluid channel, optical information of the sample particle can be obtained before or during transport.

[0016] In a preferred embodiment of the present invention, the fluid passage has a fluid flowing toward an outlet end, an ionizer is disposed at the outlet end of the fluid passage, and an ion inlet of the mass spectrometer is disposed opposite the ionizer.

[0017] According to this technical solution, the optical tweezers move between the reservoir and the inlet of the fluid passage to send a single sample particle into the inlet of the fluid passage, where the sample particle flows together with the fluid in the fluid passage to the outlet of the ionizer, and the ionized sample particle directly enters the ion inlet of the mass spectrometer for detection, thereby shortening the transport distance of the optical tweezers. Transporting the sample particles with the fluid not only ensures that the separation, identification, and optical detection of the sample particles are completed, but also further improves the transport speed of the sample particles, increases the transport throughput of the sample particles in the flow path system, and improves the detection efficiency of the analysis system.

[0018] In a preferred technical solution of the present invention, the flow path system further includes a nozzle opening formed in the fluid passage and located downstream of the reservoir, and an inkjet actuator provided corresponding to the nozzle opening, so that droplets containing sample particles are ejected one by one through the nozzle opening.

[0019] According to this technical proposal, the single cell printer (SCP) technology uses a piezoelectric inkjet to generate microdroplets that contain a single cell, enabling the separation of different cell individuals and significantly improving detection throughput. However, since cells cannot be positioned or screened during the printing process, empty droplets or droplets containing multiple cells may be generated. On the other hand, optical tweezers and an optical detector are located upstream of the flow path, and sample particles in the reservoir are captured, separated, identified, and detected before being transported to the fluid path by the optical tweezers. By setting the transport speed of the optical tweezers and the printing speed of the inkjet actuator, droplets containing single sample particles can be ejected one by one from the nozzle orifice.

[0020] In a preferred technical solution of the present invention, the fluid passage includes a first fluid passage and a second fluid passage, the outlet of the reservoir, the nozzle opening and the inkjet actuator are all connected to the first fluid passage, the ionizer is connected to the second fluid passage, and the second fluid passage has a passage opening, which is arranged corresponding to the nozzle opening and receives the droplets discharged from the nozzle opening.

[0021] According to this technical solution, droplets containing single sample particles formed by printing using an inkjet actuator pass through the nozzle opening into the second fluid passage and are ionized in the second fluid passage. This allows single sample particles to be ionized in single droplets without mutual influence, and the ionized single sample ions enter the mass spectrometer directly through the second fluid passage for detection, resulting in faster and more accurate detection. In particular, the second fluid passage may be formed as a nano-tip, and a high voltage (1-5 kV) is applied to the sample droplets via electrodes. Under the action of the high-voltage electric field, droplets containing single sample particles are ejected from the tip of the second fluid passage and become an electrospray. As long as the sample ions in the electrospray enter the sampling port of the mass spectrometer, mass spectrometry detection can be performed.

[0022] In a preferred technical solution of the present invention, the flow path system further includes a target plate disposed below the nozzle opening.

[0023] According to this technical solution, droplets containing a single sample particle are printed and formed by an inkjet actuator and dropped onto a target plate from a nozzle opening. Multiple droplets can be arranged on one target plate at the same time, allowing the multiple droplets on the target plate to be ionized and then subjected to mass spectrometry detection. In particular, the target plate on which the droplets are arranged can be used as the target plate of a matrix-assisted laser desorption ionization device to complete ionization in the matrix-assisted laser desorption ionization device.

[0024] In preferred technical versions of the present invention, the ionization device is an electrospray ion source (ESI), an atmospheric pressure chemical ionization source (APCI), an inductively coupled plasma ionization source (ICP), or a matrix-assisted laser desorption ion source (MALDI).

[0025] In a preferred technical solution of the present invention, the optical detector is one or a combination of a Raman spectrometer, an infrared spectrometer, a fluorescence spectrometer, or an optical microscope.

[0026] As a preferred technical solution of the present invention, the analysis system further includes an image recognition system for identifying sample particles from the solution.

[0027] According to this technical solution, an image recognition system can be used to extensively select and identify sample particles in a solution before capturing them, further improving the efficiency of capturing sample particles by optical tweezers and the detection speed of an optical detector.

[0028] A second aspect of the present invention is a capturing step of capturing sample particles in a solution stored or flowing in a flow channel system using optical tweezers; an optical analysis step for detecting optical information of the sample particles; and a mass spectrum detection step of transporting the sample particles to a mass spectrometer at least partially driven by optical tweezers, and detecting mass spectrum information of the sample particles.

[0029] In a preferred technical solution of the present invention, the optical analysis step is carried out simultaneously with the capture step or before the capture step. [Brief explanation of the drawings]

[0030] [Figure 1] 1 is a structural schematic diagram of an analysis system according to an embodiment of the present invention. [Figure 2] 1 is a structural schematic diagram of a preferred analysis system according to an embodiment of the present invention. [Figure 3] 1 is a structural schematic diagram of an analysis system according to a preferred embodiment of the present invention. [Figure 4] FIG. 2 is a structural schematic diagram of an analysis system according to another preferred embodiment of the present invention. [Figure 5] 1 is a flowchart of a first operating mode of an analysis method according to an embodiment of the present invention; [Figure 6] 1 is a flowchart of a second operating mode of the analysis method according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0031] Hereinafter, several embodiments of the present invention will be described with reference to the drawings. Those skilled in the art should understand that these embodiments are only used to explain the technical principles of the present invention, and do not limit the protection scope of the present invention.

[0032] [First embodiment] 1 is a structural schematic diagram of the analysis system according to this embodiment. As shown in FIG. 1, the analysis system includes a flow channel system 100, optical tweezers 200, an optical detector 300, and a mass spectrometer 400.

[0033] Here, the specific shape and structure of the flow path system 100 is not limited, and may be, for example, a housing structure that contains a fluid therein, or a plate-like structure with a grooved flow path on its surface. The fluid stored or flowing in the flow path system 100 includes a solution containing at least the sample particles 10, and the sample particles 10 are suspended in the solution. The flow path system 100 is formed into a light-transmitting structure that allows a light beam to pass through at the location where the solution is stored or flowing.

[0034] The optical tweezers 200 includes one or more laser generators 21 and emits one or more strongly focused lasers toward the fluid in the fluid flow system 100, forming an optical trap at the focused position of the one or more lasers in the fluid. A single particle (all particles in the solution, including sample particles 10) positioned in the optical trap is fixed in the optical trap by being constrained by an optical gradient force, thereby realizing the separation and capture of a single particle in the solution. Furthermore, the position of the optical trap in the fluid flow system 100 can be changed by moving the optical tweezers 200 and the fluid flow system 100 relative to each other, and the particle in the optical trap moves laterally due to the constraint of the optical gradient force. That is, the optical tweezers 200 drives the particle to move relative to the fluid flow system 100, thereby realizing particle transport within the fluid flow system 100 by the optical gradient force.

[0035] The optical detector 300 can identify and optically detect particles in a solution or particles trapped by the optical tweezers 200 by detecting the optical information of the particles. The optical detector 300 may be any device capable of identifying and detecting a single or multiple sample particles 10, such as a Raman spectrometer, an infrared spectrometer, a fluorescence spectrometer, or a combination of several types of optical microscopes. Preferably, the optical detector 300 is a Raman spectrometer, and the optical tweezers 200 can be the detection light source of the Raman spectrometer. When the optical tweezers 200 traps the sample particle 10, the Raman spectrometer can obtain information about the material components and molecular structure of the sample particle 10 based on the scattering spectrum between the laser beam of the optical tweezers 200 and the sample particle 10. This makes the device structure simpler and the detection process faster and more accurate.

[0036] The mass spectrometer 400 is provided downstream of the flow path system 100; for example, in the case of a flow path system 100 through which a fluid flows, the mass spectrometer 400 may be provided at the end of the fluid flow path to receive the ionized sample particles 10 and detect the material composition of the sample particles 10.

[0037] In this embodiment, the sample particle 10 may be any particle that can be captured by optical tweezers, such as an ion, a neutral particle, a single cell, an organelle, or a single-cell microorganism. While not particularly limited, the sample particle 10 may preferably be one or a combination of cells, organelles, and single-cell microorganisms. This allows the analytical system of this embodiment to function as an automated single-cell multidimensional analytical instrument, reducing the technical difficulty and implementation cost of comprehensive single-cell analysis while improving analytical speed. When applied to drug development and tumor treatment, spectral and mass spectral information can provide pharmacodynamic and pharmacokinetic information on single cells, respectively, enabling high-throughput drug sensitivity screening, overcoming the problem of tumor cell heterogeneity, and accelerating the research and development of anticancer drugs. When applied to fields such as biological research, spectral or immunofluorescence information can be used to quickly and accurately identify specific cells from a vast cell population. Furthermore, by manipulating the optical tweezers 200, all particles in a solution can be selected as needed, and mass analysis of the specific cells can be completed quickly and automatically. For example, circulating tumor cells can be quickly and accurately screened and analyzed from a large number of normal cells.

[0038] Specifically, a solution containing sample particles 10 is stored or flowing in a fluidic system 100, and a laser generator 21 of the optical tweezers 200 emits a laser beam toward the fluidic system 100. The laser beam is focused in the fluidic system 100 to form an optical trap, capturing and immobilizing a single sample particle 10 in the solution. Furthermore, an optical detector 300 identifies, detects, and analyzes the sample particles 10 in the solution or the sample particles 10 captured by the optical tweezers 200, providing optical information (such as material composition and material structure) of the captured sample particles 10. Based on the detection results of the optical detector 300, the optical tweezers 200 selects and captures the appropriate sample particle 10, and then uses the optical gradient force of the optical tweezers 200 to drive the single sample particle 10 and transport it to the fluidic system 100, where it flows into a downstream mass spectrometer 400 for further mass analysis.

[0039] In this embodiment, the optical tweezers 200 can capture and transport a single sample particle 10 from a solution, and simultaneously with or before the optical tweezers 200 capture and transport the single sample particle 10, the optical detector 300 can identify and detect the optical information of the sample particle 10, thereby allowing the optical detector 300 to preferentially detect particles in the solution, making it convenient to selectively capture a single target sample particle from a solution using the optical tweezers 200. Furthermore, the optical tweezers 200 can at least partially be used to laterally move the sample particle 10, allowing the single sample particle 10 to be sent to a mass spectrometer 400 for detection. Because the optical tweezers 200 are used to directly capture, detect, and transport the sample particle in situ, there is no need to manually transport the sample. The test-throughput mass analysis of the optical detector 300 can be fitted to a mass spectrometer, and the processes of identifying, capturing, controlling, and detecting the sample particle 10 can be completed quickly, accurately, and automatically.

[0040] In particular, the analytical system of this embodiment can complete the detection of both optical information and mass spectral information for a single sample particle 10 in a single analytical process, thereby simultaneously monitoring the optical properties and composition of the single sample particle 10, and particularly, in single-cell drug screening, simultaneously monitoring pharmacokinetics and pharmacodynamics at the single-cell level.

[0041] FIG. 2 is a schematic diagram showing the structure of a preferred analysis system in this embodiment.

[0042] As a preferred embodiment, as shown in FIG. 2, the flow path system 100 includes a reservoir 11 for storing a solution containing sample particles 10, and a fluid passage 12 communicating with the reservoir 11.

[0043] Here, both the fluid passage 12 and the reservoir 11 are formed with an optically transparent structure, and the fluid passage 12 has a fluid inlet 121 and a fluid outlet 122. A medium solution not containing sample particles 10 is continuously introduced into the fluid inlet 121, and the fluid outlet 122 is provided with an ionizer 13 and an ion inlet 41 of a mass spectrometer 400 installed corresponding to the ionizer 13. The ionizer 13 may be an electrospray ion source, an atmospheric pressure chemical ionization source, an inductively coupled plasma ionization source, or a matrix-assisted laser desorption ion source. Taking an electrospray ion source as an example, the fluid outlet 122 of the fluid passage 12 may be the tip of the jet tip of the electrospray ion source. After the fluid is ejected from the tip, it is ionized by the action of an electrode, and the ionized sample particles 10 enter the ion inlet 41 of the mass spectrometer 400 and are detected.

[0044] The reservoir 11 communicates with a reservoir communication port 123 in the middle of the fluid passage 12 (a portion excluding the fluid inlet 121 and the fluid outlet 122), and the solution in the reservoir 11 remains relatively stationary and is stored in the reservoir 11 when not driven by an external force. By separately installing the reservoir 11 and the fluid passage 12, it is possible to prevent sample particles 10 that have not been separated or identified from flowing together with the solution into the mass spectrometer 400 at the downstream side of the flow path system 100, and further, if the solution in the reservoir 11 remains stationary, it is possible to prevent disturbances in the solution from affecting the binding force of the optical tweezers 200.

[0045] Specifically, when capturing and controlling the sample particle 10 in the reservoir 11, the optical tweezers 200 emits a laser beam toward the solution in the reservoir 11 to capture and fix a single sample particle 10 in the solution in the reservoir 11. Then, by relative movement between the optical tweezers 200 and the flow path system 100, preferably, the laser generator 21 of the optical tweezers 200 remains stationary while the flow path system 100 moves, slowly moving the optical trap created by the optical tweezers 200 in the flow path system 100 from the reservoir 11 into the fluid passage 12. The sample particle 10 held in the optical trap moves into the fluid passage 12 along with it, is carried by the medium solution continuously flowing in the fluid passage 12, and flows toward the fluid outlet 122, where it is ionized. The ionized sample particle 10 enters the mass spectrometer 400 below for mass spectrum detection.

[0046] In this embodiment, after capturing a sample particle 10 in the reservoir 11, the optical tweezers 200 simply moves to the reservoir communication port 123 between the reservoir 11 and the fluid passage 12, where the single sample particle 10 is transported to the reservoir communication port 123 of the fluid passage 12, where it flows along with the medium solution in the fluid passage 12 to the ionizer 13 at the fluid outlet 122. The ionized sample particle 10 then enters the ion inlet 41 of the mass spectrometer 400 and is detected. This shortens the transport distance of the optical tweezers 200, and transporting the sample particle 10 by fluid ensures the completion of separation, identification, and optical detection of the sample particle 10. This further improves the transport speed of the sample particle 10, increases the transport throughput of the sample particle 10 in the flow path system 100, and improves the detection efficiency of the analysis system.

[0047] In another embodiment, as shown in FIG. 3, the fluid passage 12 includes a first fluid passage 12a and a second fluid passage 12b.

[0048] Among these, the first fluid passage 12a is formed with a fluid inlet 121, a reservoir connection port 123, and a nozzle port 124 in that order, and the fluid in the first fluid passage 12a flows in from the fluid inlet 121, carries the sample particles 10 transported by the optical tweezers 200 as it flows through the reservoir connection port 123, and then flows out from the nozzle port 124. The nozzle port 124 is a through-hole that opens into the fluid passage 12, and an inkjet actuator 125 is provided opposite the nozzle port 124 to print the fluid in the fluid passage 12 into droplets. As a result, the fluid carrying the sample particles 10 in the first fluid passage 12a is printed by the inkjet actuator 125 as droplets that enclose a single sample particle 10, and these droplets flow out of the first fluid passage 12a one by one from the nozzle port 124.

[0049] The second fluid passage 12b has a passage opening 126 facing the inkjet actuator 125 across the nozzle opening 124 so as to receive droplets containing sample particles 10 ejected one by one from the nozzle opening 124. The end of the second fluid passage 12b is an ionizer 13 serving as an electrospray ion source. The air pressure at the end of the second fluid passage is lower than that at the passage opening 126, and the sample particles 10 flow together with the solution toward the ionizer 13 due to the air pressure difference. The end of the second fluid passage 12b is formed as a nano-tip, and a high voltage (1-5 kV) is applied to the sample particles 10 via electrodes. Under the action of the high-voltage electric field, droplets containing single sample particles 10 are ejected from the tip of the second fluid passage 12b to form an electrospray. As long as the sample ions in the electrospray enter the ion inlet 41 of the mass spectrometer 400, mass spectrometry detection can be performed.

[0050] In this embodiment, optical tweezers 200 and an optical detector 300 are provided upstream of the flow channel system 100. After the sample particles 10 in the reservoir 11 are captured, separated, identified, and detected, they are transported to the fluid channel 12 by the optical tweezers 200. By setting the transport speed of the optical tweezers 200 and the printing speed of the inkjet actuator 125, droplets containing single sample particles 10 can be ejected one by one from the nozzle opening 124. The droplets containing single sample particles 10 printed by the inkjet actuator 125 enter the passage opening 126 of the second fluid channel 12b from the nozzle opening 124 and are ionized in the second fluid channel 12b. This allows the single sample particles 10 to be ionized in a single droplet without mutual influence, and the ionized single sample ions enter the mass spectrometer 400 directly from the second fluid channel 12b for detection, which is faster and more accurate.

[0051] 4, the flow channel system 100 further includes a target plate 127, which is provided below the nozzle opening 124. A droplet containing a single sample particle 10 formed by printing with the inkjet actuator 125 is dropped onto the target plate 127 from the nozzle opening 124, and multiple droplets can be arranged simultaneously on one target plate 127, thereby enabling the multiple droplets on the target plate 127 to be ionized and then subjected to mass spectrometry detection.

[0052] In particular, the target plate 127 on which the droplets are arranged can be used as the target plate 127 of a matrix-assisted laser desorption / ionization device, and the ionization of a plurality of droplets on the target plate 127 can be completed in the matrix-assisted laser desorption / ionization device.

[0053] In a preferred embodiment of the present invention, the analysis system further includes an image recognition system (not shown) for identifying the sample particles 10 from the solution. The image recognition system may be an image recognition device such as an optical microscope or an optical camera, and the image recognition system allows for a wider range of identification and sorting of the sample particles 10 in the solution before capturing the sample particles 10, thereby further improving the efficiency of capturing the sample particles 10 by the optical tweezers 200 and the detection speed of the optical detector 300.

[0054] [Second embodiment] The second embodiment of the present invention is A capture step S1 of capturing sample particles in a solution stored or flowing in a flow channel system using optical tweezers; an optical analysis step S2 of detecting optical information of the sample particles; and a mass spectrum detection step S3 of transporting the sample particles to a mass spectrometer at least partially driven by the optical tweezers, and detecting mass spectrum information of the sample particles.

[0055] Preferably, the optical analysis step S2 is performed simultaneously with the capture step S1 or before the capture step S1.

[0056] The analytical method of this embodiment may be applied to the analytical system of the first embodiment, or to an analytical system combined with other optical tweezers, an optical detector, and a mass spectrometer. Figures 5 and 6 respectively show two operating modes of the analytical method of this embodiment, and the two operating modes of the analytical method of this embodiment will be described below using the analytical system of the first embodiment in Figure 2 as an example.

[0057] As shown in FIG. 5, when detecting and analyzing sample particles 10 in a reservoir 11, an optical analysis step S2 is first performed. For example, assuming that the optical detection device is a fluorescence microscope, a target sample particle (single cell) is first detected and found in the solution by fluorescence. Next, a capture step S1 is performed in which the optical tweezers 200 emits a laser beam toward the solution in the reservoir 11 to capture and fix a single sample particle 10 in the solution in the reservoir 11. Then, a mass spectrum detection step S3 is performed based on the identification and detection results of the optical analysis step S2. Relative movement occurs between the optical tweezers 200 and the fluid path system 100, and the sample particle 10 identified by the optical detector 300 is moved from the reservoir 11 to the fluid path 12 under the drive of an optical gradient force. The sample particle 10 is carried by the continuously flowing fluid in the fluid path 12 toward the fluid outlet 122, where it is ionized. The ionized sample particle 10 enters the mass spectrometer 400 below for mass analysis.

[0058] Alternatively, as shown in Fig. 6, when detecting and analyzing sample particles 10 in a liquid reservoir 11, a capture step S1 is first performed. A laser beam is emitted toward the solution in the liquid reservoir 11 by optical tweezers 200 to capture and fix a single sample particle 10 in the solution in the liquid reservoir 11. Simultaneously with performing the capture step S1, an optical analysis step S2 is performed in which the laser beam of the optical tweezers 200 is used as a detection light source and an optical detector 300 detects and analyzes the sample particle 10 captured by the optical tweezers 200, identifying the sample particle 10 in the solution and detecting optical information (such as material composition and material structure) of the sample particle 10. Thereafter, a mass spectrum detection step S3 is performed. Relative movement is generated between the flow path system 100, and the sample particles 10 identified by the optical detector 300 are moved from the reservoir 11 to the fluid path 12 under the drive of the optical gradient force, and the sample particles 10 flow within the fluid path 12 toward the fluid outlet 122, where they are ionized. The ionized sample particles 10 enter the mass spectrometer 400 below and undergo mass analysis.

[0059] Although the technical solutions of the present invention have been described above in conjunction with the drawings, it is obvious to those skilled in the art that the scope of protection of the present invention is not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent modifications or substitutions to the relevant technical features, and all of these modifications or substitutions fall within the scope of protection of the present invention. [Explanation of symbols]

[0060] 100 fluidic system; 10 sample particles; 11 reservoir; 12 fluid passage; 12a first fluid passage; 12b second fluid passage; 121 fluid inlet; 122 fluid outlet; 123 reservoir communication port; 124 nozzle port; 125 inkjet actuator; 126 passage opening; 127 target plate; 13 ionizer; 200 optical tweezers; 21 laser generator; 300 optical detector; 400 mass spectrometer; 41 ion inlet

Claims

1. 1. An analytical system comprising: a flow path system in which a solution containing a plurality of sample particles is stored or flows; optical tweezers that are disposed toward the flow channel and capture a single sample particle from the plurality of sample particles in the flow channel; an optical detector that detects optical information of the single sample particle in the flow channel system while the single sample particle is trapped by the optical tweezers; a mass spectrometer installed downstream of the flow path system, identifying the plurality of sample particles and selecting a single target sample particle based on the optical information; An analytical system, wherein the single target sample particle is transported to the mass spectrometer at least partially by driving the optical tweezers in the flow path system.

2. The analytical system according to claim 1 , wherein the plurality of sample particles are one or a combination of cells, organelles, and single-cell microorganisms.

3. the flow path system includes a reservoir that stores the solution and a fluid passage that communicates with the reservoir; 2. The analytical system of claim 1, wherein the optical tweezers move the single sample particle from the reservoir to the fluid passage at least in part by utilizing an optical gradient force by moving relative to the reservoir and the fluid passage.

4. 4. The analysis system of claim 3, wherein the fluid passage has a fluid flowing toward an outlet end, an ionization device is installed at the outlet end of the fluid passage, and an ion inlet of the mass spectrometer is provided opposite the ionization device.

5. The flow path system includes: a nozzle orifice formed in the fluid passage and located downstream of the reservoir; an inkjet actuator provided corresponding to the nozzle opening, 5. The analytical system of claim 4, wherein the droplets each having a single sample particle are ejected one by one through the nozzle opening.

6. 6. The analytical system of claim 5, wherein the fluid passage includes a first fluid passage and a second fluid passage, the outlet of the reservoir, the nozzle opening, and the inkjet actuator are all connected to the first fluid passage, the ionizer is connected to the second fluid passage, and the second fluid passage has a passage opening, the passage opening is provided corresponding to the nozzle opening, and receives the droplets discharged from the nozzle opening.

7. The analytical system according to claim 5 , wherein the flow path system further includes a target plate provided below the nozzle opening.

8. 5. The analytical system of claim 4, wherein the ionization device is an electrospray ion source, an atmospheric pressure chemical ionization source, an inductively coupled plasma ionization source, or a matrix-assisted laser desorption ion source.

9. 2. The analytical system of claim 1, wherein the optical detector is one or a combination of a Raman spectrometer, an infrared spectrometer, a fluorescence spectrometer, or an optical microscope.

10. The analytical system of claim 1 further comprising an image recognition system for identifying the plurality of sample particles from the solution.

11. a capturing step of capturing a single sample particle from a plurality of sample particles in a solution stored or flowing in a flow channel system using optical tweezers; an optical analysis step of detecting optical information of the single sample particle while the single sample particle is trapped by the optical tweezers; a sorting step of identifying the plurality of sample particles and sorting a single target sample particle based on the optical information; and a mass spectrum detection step of transporting the single target sample particle to a mass spectrometer at least in part by driving the optical tweezers, and detecting mass spectrum information of the single target sample particle.

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