A single particle elemental and isotopic analysis system and method

Abstract

The application discloses a single-particle element and isotope analysis system and method, and the system comprises a mass spectrometer, a high-speed ion counting detector, a high-speed oscilloscope and a data processing system; the mass spectrometer and the high-speed ion counting detector are connected through corresponding connecting lines; the high-speed ion counting detector and the high-speed oscilloscope are connected through corresponding connecting lines; and the high-speed oscilloscope and the data processing system are connected through corresponding connecting lines.The method is as follows: the high-speed ion counting detector counts the number of received ions and outputs in the form of current; the oscilloscope continuously scans the signal at the output end of the detector by adopting a time window and nanosecond-level acquisition speed, and saves the signal meeting the trigger condition in the time window; and the data processing system processes the data stored by the oscilloscope to obtain multi-dimensional information of single particles and statistical results of particles in the same batch.The application can be applied to the field of analysis and detection instruments, and can obtain the signal detailed profile of single particles, element and isotope analysis, particle size and other results.

Description

Technical Field

[0001] This invention relates to the field of mass spectrometry, and more particularly to a system and method for elemental and isotopic analysis of single particles. Background Technology

[0002] Nanoparticles, ranging from nanometers to micrometers, play a crucial role in the entire geodynamic system, yet our understanding of them remains incomplete. While elemental and isotopic information about particulate matter contains rich details about sample origin and transport processes, individual particles exhibit significant specificity. Furthermore, isotopic information at the whole-sample level masks the differences in elemental and isotopic composition between individual particles, neglecting their unique characteristics. Therefore, establishing a multi-dimensional and accurate method for analyzing the elemental and isotopic composition of particulate matter at the individual particle level is of great significance for exploring the origin and cycle of particulate matter, as well as its interactions with the environment and organisms.

[0003] Single-particle (cell) inductively coupled plasma mass spectrometry (spICP-MS) is a high-temporal-resolution ICP-MS analytical mode that provides a new approach for elemental and isotope analysis of single particles (cells). Existing spICP-MS detectors are low-dead-time ion counters, typically represented by secondary electron multipliers. Limited by the traditional testing requirements of mass spectrometers, these ion counters rely on a dwell / integration time of tens to hundreds of milliseconds, counting the number of ion peaks per unit dwell / integration time and outputting the results in CPS format. The fundamental principle of spICP-MS is based on the fact that particles (cells) generate a pulse signal peak within one or several dwell / integration times. This pulse signal peak is significantly higher than the instantaneous signals of background and dark noise for a short period. Statistical analysis of these pulse signal peaks yields the statistical results for single-particle analysis. However, the use of dwell / integration time brings many intractable problems to single-particle analysis: (1) After each dwell / integration time, a certain amount of time is needed to count the number of ion peaks, resulting in a blind time during which the detector output signal cannot be collected, causing signal loss, which is fatal for single-particle (cell) events lasting only a few hundred microseconds; (2) Short dwell / integration time leads to decreased sensitivity and stability. The shortest dwell / integration time of a mature mass spectrometer detector can only be set to tens of microseconds. A single-particle event is divided into several intervals for displaying contour details, but the number of ion peaks counted within a short dwell / integration time is limited. The sub-signal intensity is very low, which significantly reduces the signal-to-noise ratio, making it difficult to detect small particle samples. Moreover, when the residence / integration time is set to an extremely short time, the overall stability of the detector system is very poor, and the analysis results fluctuate greatly. (3) Long residence / integration time will greatly increase the probability of split particle events and multiple particle simultaneous arrival events, which will cause errors in the test results on the one hand, and cause the analytical throughput of the method to decrease rapidly on the other hand. (4) The optimization process of residence / integration time is very difficult. High stability, high sensitivity and high resolution accurate acquisition of single particle profiles are two contradictory directions for residence / integration time, which are difficult to achieve at the same time. The existence of these problems seriously restricts the ability of spICP-MS to perform multi-element / isotope analysis of single particles (cells), limits the development of single particle (cell) analysis related technologies, and the solution of related major scientific problems. Therefore, developing a high-throughput, high-sensitivity, high-accuracy and high-precision single particle (cell) analysis method is the top priority to solve the above problems. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention constructs an "Event Triggered Capture" (ETSC) system that combines a high-speed oscilloscope with a mass spectrometer. The purpose of this invention is to provide high-throughput, high-sensitivity, high-accuracy, and high-precision analysis of elements and isotopes in individual particles (cells).

[0005] This invention leverages the advantages of high-speed oscilloscopes, such as high throughput, large storage depth, and high acquisition frequency, to comprehensively collect signal profiles of specific elements and isotope signal clusters in single particles (cells) after mass spectrometry screening. It simultaneously achieves two major functions: high sensitivity, lossless signal acquisition, and single-particle (cell) event profile acquisition. Furthermore, the ETSC system possesses high analytical throughput capabilities; when used in conjunction with a multi-detector channel, high-ion extraction-efficiency MC-ICP-MS, it can achieve precise determination of element / isotope ratios in nanoparticles (cells) with sizes ranging from several nanometers. This invention solves the difficulties of multi-element / isotope analysis in single particles (cells) from both hardware and principle perspectives, providing a technical means to address major scientific problems related to single particles / single cells. This method also has guiding significance for the development of single-particle (cell) mass spectrometry instruments.

[0006] Specifically, this invention proposes a single-particle elemental and isotopic analysis system, the system comprising:

[0007] Mass spectrometer, high-speed ion counting detector, high-speed oscilloscope and data processing system;

[0008] The mass spectrometer and the high-speed ion counting detector are connected via corresponding connecting lines;

[0009] The high-speed ion counting detector is connected to the high-speed oscilloscope via corresponding connecting lines;

[0010] The high-speed oscilloscope is connected to the data processing system via corresponding connection cables.

[0011] A method for elemental and isotopic analysis of a single particle, applied to the aforementioned elemental and isotopic analysis system for a single particle, includes the following steps:

[0012] S1. Electrically connect the mass spectrometer to the high-speed ion counter detector; connect the input channel of each high-speed oscilloscope to one detection channel of the high-speed ion counter, and configure the trigger acquisition conditions of the high-speed oscilloscope;

[0013] S2. The particulate matter sample is processed into a colloidal / suspension, and then atomized using a nebulizer to convert the large volume of liquid into small droplets containing particulate matter, which are then sprayed into an ICP ionization system for ionization. A mass analyzer is used to screen out ion clusters composed of specific isotopes to obtain the screened ion clusters.

[0014] S3. Based on the trigger acquisition conditions of the high-speed oscilloscope, each high-speed oscilloscope channel collects the electrical signal transmitted by the corresponding high-speed ion counting detector and records the original signal profile generated by the ion clusters after screening within a dynamic time window; the original signal profile is simultaneously converted into a simplified signal by the high-speed oscilloscope.

[0015] S4. The data processing system statistically simplifies the multi-dimensional information of a single particle in the signal and the statistical information of a large number of particles in the same batch, and outputs the information.

[0016] The beneficial effects provided by this invention are:

[0017] (1) The analysis system (ETSC system) described in this invention is a system for acquiring single-particle (cell) events without signal loss. The acquisition rate of the ETSC system can reach or even exceed 500 picoseconds / point, and can completely record the pulse current signal generated by each ion bombarding the detector when the ions generated by a single particle (cell) arrive at the detector. Therefore, this method completely records the ion clusters of single particles (cells) after ICP ionization without any loss of counting signal, realizing more accurate and higher precision single-particle event collection. The obtained single-particle (cell) event profile is also used to remove erroneous events collected, further improving the accuracy of subsequent analysis results.

[0018] (2) The ETSC system described in this invention is a highly efficient system for identifying single-particle (cell) events. Compared with conventional systems, the ETSC system sets triggering conditions for single-particle (cell) events. Only when the ion clusters after ionization of a single particle (cell) generate densely occurring pulse peaks in the detector can they be specifically identified and stored by the oscilloscope. Signals that do not meet this condition cannot trigger the oscilloscope and therefore will not be saved, thus avoiding the acquisition of redundant background and reducing the difficulty of data processing.

[0019] (3) The ETSC system described in this invention is a high-throughput single-particle (cell) analysis system. Compared with the detectors used in conventional methods, the frame-to-frame refresh time of the time window in the ETSC system is very short (~1μs), which can be regarded as a technique for continuously scanning the detector output signal; it has been verified that the ETSC system can identify more than 900 events per second when analyzing single-particle events, which is an analysis speed that is difficult for other systems to achieve.

[0020] (4) The ETSC system described in this invention is a highly sensitive single-particle (cell) analysis system. Compared with the traditional method that uses residence time, the oscilloscope in this system records single-particle (cell) events acquired by the detector without loss, and can identify nanoparticle (cell) signals in solution under the presence of high concentrations of ions, significantly reducing the interference of background ions; theoretically, the ETSC system achieves signal collection of a single ion; when the ETSC system is used in conjunction with a conventional MC-ICP-MS, the minimum particle size that can be reliably collected and analyzed reaches 8 nm, and the absolute detection mass reaches 2.80 atk.

[0021] (5) The ETSC system described in this invention is a high-accuracy and high-precision single-particle (cell) analysis system. Compared with traditional systems, this system can non-destructively acquire the ion signals generated by the transient process of a single particle (cell) detected by a high-speed detector. Therefore, it can more accurately analyze the number of elements and isotopes in the transient signals generated by a single particle (cell), thereby achieving more accurate and higher-precision particle size analysis and determination of element / isotope ratios.

[0022] (6) The ETSC system described in this invention is an easily implemented single-particle (cell) analysis system. Compared with other single-particle (cell) methods, this method does not change the basic structure of the mass spectrometer, but only requires changing the output mode of the detector. Therefore, this invention is applicable to all existing mass spectrometers based on high-speed ion counting detectors and has strong scalability. In addition, this invention does not involve complex mathematical calculations and data processing, making it user-friendly and facilitating the market promotion of this invention. Attached Figure Description

[0023] Figure 1 This is a basic structural diagram of the system of the present invention.

[0024] Figure 2 This is a single-particle event profile obtained by the present invention.

[0025] Figure 3 This invention provides a time-count cumulative plot of a single particulate matter, as well as the total count intensity, isotope ratio, and event duration.

[0026] Figure 4 This invention provides high-sensitivity analysis verification and small-diameter (10nm) single-particle events.

[0027] Figure 5 This is the original contour map of the error event identification and elimination capability and the simultaneous arrival of two particles obtained by the present invention.

[0028] Figure 6 This invention provides the particle size calculation capability.

[0029] Figure 7 It is the ability to calculate the quantity concentration obtained.

[0030] Figure 8 This refers to the measurement of the obtained isotope ratios. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be further described below with reference to the accompanying drawings.

[0032] This invention provides a single-particle elemental and isotopic analysis system, comprising:

[0033] Mass spectrometer, high-speed ion counting detector, high-speed oscilloscope and data processing system;

[0034] The mass spectrometer and the high-speed ion counting detector are connected via corresponding connecting lines;

[0035] The high-speed ion counting detector is connected to the high-speed oscilloscope via corresponding connecting lines;

[0036] The high-speed oscilloscope is connected to the data processing system via corresponding connection cables.

[0037] The mass spectrometer is equipped with: a nebulizer injection system, an ICP ionization system, and a mass analyzer.

[0038] The suspension or colloidal solution of particulate matter samples is dispersed into micron-sized droplets encapsulating individual particulate cells by the atomization injection system;

[0039] The particulate samples include metal-based nanoparticles, natural nanominerals with nano to micron sizes, single cells, and other samples existing in the form of microparticles / droplets.

[0040] The micron-sized droplets are introduced into the ICP ionization system for ionization, resulting in an ion cluster with sparse edges and a dense center.

[0041] The mass analyzer is used to screen out ion clusters composed of specific isotopes to obtain the screened ion clusters.

[0042] As one embodiment, the mass spectrometer is used to disperse a suspension / colloidal solution of particulate (cell) samples into micron-sized droplets encapsulating individual particles, and introduce them into an ICP for ionization. Each particle (cell) is ionized into an ion cluster with sparse edges and a dense center. Ion clusters composed of specific isotopes are screened out in the mass analyzer and transmitted to the back-end detector. In addition, this system is also suitable for other single-particle (cell) sample introduction methods such as laser ablation and microfluidic chips.

[0043] The high-speed ion counting detector is used to detect the screened ion clusters transmitted by the mass spectrometer and convert them into current / voltage pulses.

[0044] It should be noted that the mass spectrometer is equipped with a high-speed ion counting detector, which is used to collect the signals of the isotopic ions transmitted from the mass spectrometer. The high-speed ion counting detector converts an ion into a current / voltage pulse through the principle of secondary electron multiplication and outputs the signal from the output terminal.

[0045] The high-speed oscilloscope visualizes the current / voltage pulses as pulse signal peaks and converts the pulse signal peaks into simplified signals.

[0046] It should be noted that the output of the high-speed ion counting detector is connected to the channel of a high-speed oscilloscope. The high-speed oscilloscope has 4 to 8 input channels, each of which can be connected to a high-speed ion counting detector. The high-speed oscilloscope has an adjustable dynamic time window, which is set with trigger conditions matching single-particle (cell) ion clusters. When the ion cluster generated by a single particle (cell) reaches the high-speed ion counting detector and outputs a specific pulse signal, the high-speed oscilloscope records the original signal profile of the single-particle ion cluster within 1 to 2 ms of the dynamic time window at a nanosecond acquisition speed. The digital oscilloscope has online mathematical processing capabilities to convert the original signal profile into a simplified signal profile composed of -1 and 1 and save it.

[0047] The data processing system processes the simplified signal to obtain multi-dimensional information, including the particle size and isotope ratio of individual particles, and statistically analyzes a large number of particles in the same batch to obtain statistical results.

[0048] It should be noted that the data processing system processes the data stored in the oscilloscope to obtain multi-dimensional information such as the elements and isotope ratios of individual particles (cells), and statistically analyzes a large number of particles (cells) in the same batch to obtain statistical results.

[0049] As an example, the mass spectrometer should include all existing mass spectrometers using high-speed ion counting detectors and related detectors. In this invention, the most suitable example is the MC-ICP-MS instrument, which is used to demonstrate the effect of the invention.

[0050] As one embodiment, the high-speed oscilloscope includes existing commercial oscilloscopes and other hardware modules based on similar principles; the high-speed ion counting detector of claim 1 can be directly connected to the oscilloscope, or it can be first connected to hardware such as a signal amplifier and a signal discriminator before being connected to the oscilloscope to achieve better analysis results.

[0051] The high-speed oscilloscope continuously scans the signal output by the high-speed ion counting detector within a dynamic time window with adjustable duration, and displays and stores all data points within that time window when the trigger acquisition conditions are met. The trigger acquisition conditions include: the number of peaks per unit time reaching a preset threshold and the interval between adjacent peaks reaching a preset threshold.

[0052] As one embodiment, the high-speed oscilloscope records single-particle (cell) signals by continuously scanning the detector output signal with a dynamic time window of adjustable duration, and displaying and storing all data points within the time window when the trigger acquisition conditions are met, i.e., the original outline of the instantaneous signal of a single particle (cell). Other principles and hardware that achieve similar analysis effects are also included within the scope of this patent. The trigger conditions of the high-speed oscilloscope include the number of peaks per unit time as a threshold, the interval time between adjacent peaks as a threshold, and similar threshold settings as trigger conditions are also included within the scope of this invention.

[0053] It should also be noted that the online mathematical calculation function of the high-speed oscilloscope processes the original signal profile into a simplified signal diagram, including but not limited to processing it into the form of -1 and 1, as well as simplified signal diagrams obtained by other mathematical processing, and also includes cases where the original profile is used directly for data analysis without mathematical processing.

[0054] The raw and simplified signals obtained by the high-speed oscilloscope can be used to identify and eliminate erroneous single-particle (cell) events; the erroneous events include false positive events that affect accurate analysis, such as dissolved ion false triggering events, simultaneous arrival of multiple particles (cells) events, detector saturation events, and incomplete particulate (cell) events.

[0055] The specific process by which the data processing system processes the simplified signal is as follows:

[0056] The data processing system first converts single-particle events into a cumulative count graph that changes over time;

[0057] Multidimensional information, including the particle size and isotope ratio of individual particles, can be directly obtained from the cumulative count plot that changes over time.

[0058] As one embodiment, the data processing system first converts a single particle (cell) event into a time-cumulative count map; the time-cumulative count map can directly obtain multi-dimensional information about a single particle (cell), such as the count signal value in a single mass spectrometer detector channel, the element / isotope count signal ratio between multiple channels, and the duration of a single particle (cell) event.

[0059] A method for elemental and isotopic analysis of a single particle, applied to a single-particle elemental and isotopic analysis system.

[0060] The method includes the following steps:

[0061] S1. Electrically connect the mass spectrometer to the high-speed ion counter detector; connect the input channel of each high-speed oscilloscope to one detection channel of the high-speed ion counter, and configure the trigger acquisition conditions of the high-speed oscilloscope;

[0062] It should be noted that the mass spectrometer is equipped with a high-speed ion counting detector. In practice, the high-speed oscilloscope is coupled to the detector of the mass spectrometer: each detector of the tuned mass spectrometer is directly connected to a detection channel of the high-speed oscilloscope, and the acquisition conditions of the oscilloscope are configured.

[0063] S2. The particulate matter sample is processed into a colloidal / suspension, and then atomized using a nebulizer to convert the large volume of liquid into small droplets containing particulate matter, which are then sprayed into an ICP ionization system for ionization. A mass analyzer is used to screen out ion clusters composed of specific isotopes to obtain the screened ion clusters.

[0064] S3. Based on the trigger acquisition conditions of the high-speed oscilloscope, each high-speed oscilloscope channel collects the electrical signal transmitted by the corresponding high-speed ion counting detector and records the original signal profile generated by the ion clusters after screening within a dynamic time window; the original signal profile is simultaneously converted into a simplified signal by the high-speed oscilloscope.

[0065] It should be noted that the oscilloscope acquires signals from single-particle (cell) samples: according to the set oscilloscope trigger acquisition conditions, each oscilloscope channel collects the current signal transmitted by the corresponding detector. The oscilloscope records the cluster-type raw signal generated by the ionization of single particles (cells) in a time window. Then, the oscilloscope's online mathematical processing function is used to quickly and in real time process the raw signal into a simplified signal diagram composed of -1 and 1.

[0066] S4. The data processing system statistically simplifies the multi-dimensional information of a single particle in the signal and the statistical information of a large number of particles in the same batch, and outputs the information.

[0067] It should be noted that the simplified signal map data obtained is imported into a computer program, and information such as the number of ion pulse peaks, isotope ratios, and duration of single particle (cell) events in all channels of the simplified map are statistically analyzed, and the results are output to a specified table. Furthermore, the information on individual particles (cells) collected in the table is summarized and statistically analyzed to obtain information such as element / isotope ratio precision, particle size distribution, and number concentration.

[0068] As one embodiment, the basic system structure diagram in this case is as follows: Figure 1 As shown.

[0069] The mass spectrometer 1 is equipped with multiple high-speed ion detectors 2, each of which is connected to a signal input channel of a high-speed oscilloscope 3, forming an ETSC system for single-particle analysis.

[0070] The ETSC system uses a dynamic time window to scan the detector output signal and specifically identifies ion clusters generated by single-particle events by setting the oscilloscope trigger conditions. In this case, the sample to be tested is a silver nanoparticle standard solution. The tuning and optimization of MC-ICP-MS are completed by the detector and the conventional ion counting system. The trigger condition of the high-speed oscilloscope is set to the rising edge signal formed by two ion pulse peaks observed by the ETSC system within 25ns. The dynamic time window length is set to 1ms.

[0071] The specific operation steps of this invention are as follows:

[0072] (1) Coupling of high-speed oscilloscope and mass spectrometer detector: In this case, the traditional mass spectrometer detector structure and dissolved ion standard solution were first used to optimize signal intensity and stability, and tune instrument parameters. In the traditional structure, the signal output from the electron multiplier (SEM) is amplified and discriminated, and then input to a counter circuit board for ion counting statistical analysis per unit time. This unit time is defined as the integration time. The shortest integration time of the mass spectrometer used in this case is 100ms. Under this condition, the optimal instrument conditions for MC-ICP-MS were optimized. Under the optimal instrument parameter conditions, the magnetic field position of MC-ICP-MS was fixed to ensure that the two isotopes of silver ( 107 Ag and 109 The Ag signal can be monitored by two SEMs in time-resolved mode. 107 Ag strength value, 109 Ag strength value and 109 / 107 The Ag value should be set for 5–10 minutes to ensure that the standard deviation of the signal strength is within 1%. 109 / 107 The Ag value is close to 0.9290. Subsequently, the output of the detector is disconnected from the counter circuit, and a BNC cable is used to connect it to the detection channel of the oscilloscope, completing the connection of the hardware part of the invention.

[0073] (2) Introduction of single-particle samples: 0.5 g of solid particles were added to 50 mL of deionized water. Large particles larger than micrometers were removed by ultrasonic centrifugation. The supernatant after centrifugation was collected, and 0.1% (m / v) sodium citrate was added as a suspension stabilizer to prepare a solid suspension sample. The sample was then diluted with deionized water by 10 μL. 5 ~10 7The appropriate particulate number concentration is determined by dilution; liquid colloidal suspensions can be directly diluted to a suitable dilution factor for later use. The suspension sample is converted into small droplets containing solid particles via pneumatic atomization, sprayed into a vortex chamber, and introduced into the ICP to complete the particulate ionization process. During this process, each solid particle forms an ion cloud with sparse edges and a dense center within the ICP. Within the instrument, these ion clusters are focused by an ion lens, accelerated by an electric field, and filtered by a mass analyzer before finally reaching the high-speed ion counting detector.

[0074] (3) Oscilloscope acquires single-particle sample signal: Set the oscilloscope's time window length to 1ms, the trigger condition to multi-edge triggering, and the rising edge interval between adjacent pulse peaks to 25ns. After this condition is met five times, the oscilloscope is triggered to save and display the signal waveform before and after the current trigger point position for a total of 1ms. After the ion clusters mentioned in step (2) reach the detector, a large number of ions bombard the SEM, generating hundreds to thousands of pulse peaks in hundreds of microseconds. Each pulse peak represents an ion bombardment of the SEM detector. At this time, there are locally dense pulse peaks in the detector output signal. These densely existing pulse peaks trigger the oscilloscope to acquire and store the signal. The original contour map of a 60nm silver nanoparticle is as follows. Figure 2 As shown in -a. Subsequently, using the oscilloscope's real-time mathematical processing capabilities, the original contour was transformed into a simplified single-particle diagram that is easier to observe and calculate. Figure 2 -b) This simplified diagram provides a clearer view of individual events. Erroneous individual events are eliminated using the simplified diagram, and the remaining correct events are saved in a document for subsequent calculations and statistical analysis.

[0075] (4) Individual particle data processing: The simplified signal map data obtained in (3) is imported into a computer program written in Python to process and obtain a time-related time-count cumulative plot. The time-count cumulative plot obtained by processing the 60nm silver nanoparticles in step (3) is shown below. Figure 3 As shown, analyze the number of ion pulse peaks (total value), isotope ratio, and duration of single-particle events of ion clusters in all channels of the time-count cumulative graph, and output the results to a specified table;

[0076] (5) Data statistics and analysis: The information on individual particulate matter collected in the table in (4) is summarized and statistically analyzed to obtain information such as element / isotope ratio precision, particle size distribution, and number concentration.

[0077] The following are several operational examples demonstrating the beneficial effects of this invention:

[0078] (1) Connecting an oscilloscope to a mass spectrometer enables high-sensitivity analysis. Figure 4The original profile of 10 nm silver nanoparticles is shown with a total count intensity of 100 in the dual channels, which demonstrates the high sensitivity of the system. Calculations show that the method can theoretically observe single ions, and can detect silver nanoparticles with a minimum particle size of 8 nm when the total count intensity threshold is 50.

[0079] (2) The oscilloscope is connected to the mass spectrometer to eliminate erroneous events. Erroneous events such as simultaneous arrival of multiple particles, strong signals causing detector failure, and incomplete single-particle events can lead to deviations in the statistical analysis results of single particles. The ETSC system eliminates these erroneous events by observing the original profile map. Figure 5 An example of a simultaneous arrival of multiple particles observed by the ETSC system is shown; this event was removed in subsequent analysis steps.

[0080] (3) Connecting the oscilloscope to the mass spectrometer enables high-throughput analysis. Figure 1 The medium mass spectrometer 1 and the high-speed ion detector 2 are replaced with a waveform generator. The waveform generator continuously emits waveforms at 1ms intervals, each waveform consisting of 1000 pulse peaks and lasting 200μs. These waveforms are used to simulate single-particle events entering the signal output of detector 3 at a fixed frequency. The oscilloscope 3 can monitor 100 simulated single-particle events within 110ms. The calculated analytical throughput of this invention is 900 particle events per second.

[0081] (4) The oscilloscope and mass spectrometer are used together to achieve single particle size and number concentration analysis. Figure 6 The linear relationship between the total count intensity and particle size cube of silver nanoparticles at 20 nm, 60 nm, and 100 nm was demonstrated, proving the ability of this method to perform size analysis. Figure 7 The linear relationship between the number of single-particle events detected by the ETSC system per unit time and the concentration of particulate matter in the sample solution was demonstrated, proving the ability of this method to perform particulate matter number concentration analysis in samples.

[0082] (5) Using an oscilloscope and a mass spectrometer together enables high-precision analysis of single-particle isotopes. Figure 8 -a represents the isotope ratio distribution of the 200 100nm silver nanoparticles obtained, and the calculated standard deviation is 0.019; Figure 8 -b represents the standard error of the isotope ratio of 200 100 nm silver nanoparticles obtained from statistical analysis. The standard error of 200 particles can reach 1%.

[0083] The beneficial effects of this invention are:

[0084] (1) The analysis system (ETSC system) described in this invention is a system for acquiring single-particle (cell) events without signal loss. The acquisition rate of the ETSC system can reach or even exceed 500 picoseconds / point, thus it can completely record the pulse current signal generated by each ion bombarding the detector when the ions generated by a single particle (cell) arrive at the detector. Therefore, this method completely records the ion clusters of single particles (cells) after ICP ionization without any loss of counting signal, achieving more accurate and higher precision single-particle event collection. The obtained single-particle (cell) event profile is also used to remove erroneous events collected, further improving the accuracy of subsequent analysis results.

[0085] (2) The ETSC system described in this invention is a highly efficient system for identifying single-particle (cell) events. Compared with conventional systems, the ETSC system sets triggering conditions for single-particle (cell) events. Only when the ion clusters after ionization of a single particle (cell) generate densely occurring pulse peaks in the detector can they be specifically identified and stored by the oscilloscope. Signals that do not meet this condition cannot trigger the oscilloscope and therefore will not be saved, thus avoiding the acquisition of redundant background and reducing the difficulty of data processing.

[0086] (3) The ETSC system described in this invention is a high-throughput single-particle (cell) analysis system. Compared with the detectors used in conventional methods, the frame-to-frame refresh time of the time window in the ETSC system is very short (~1μs), which can be regarded as a technique for continuously scanning the detector output signal; it has been verified that the ETSC system can identify more than 900 events per second when analyzing single-particle events, which is an analysis speed that is difficult for other systems to achieve.

[0087] (4) The ETSC system described in this invention is a highly sensitive single-particle (cell) analysis system. Compared with the traditional method that uses residence time, the oscilloscope in this system records single-particle (cell) events acquired by the detector without loss, and can identify nanoparticle (cell) signals in solution under the presence of high concentrations of ions, significantly reducing the interference of background ions; theoretically, the ETSC system achieves signal collection of a single ion; when the ETSC system is used in conjunction with a conventional MC-ICP-MS, the minimum particle size that can be reliably collected and analyzed reaches 8 nm, and the absolute detection mass reaches 2.80 atk.

[0088] (5) The ETSC system described in this invention is a high-accuracy and high-precision single-particle (cell) analysis system. Compared with traditional systems, this system can non-destructively acquire the ion signals generated by the transient process of a single particle (cell) detected by a high-speed detector. Therefore, it can more accurately analyze the number of elements and isotopes in the transient signals generated by a single particle (cell), thereby achieving more accurate and higher-precision particle size analysis and determination of element / isotope ratios.

[0089] (6) The ETSC system described in this invention is an easily implemented single-particle (cell) analysis system. Compared with other single-particle (cell) methods, this method does not change the basic structure of the mass spectrometer, but only requires changing the output mode of the detector. Therefore, this invention is applicable to all existing mass spectrometers based on high-speed ion counting detectors and has strong scalability. In addition, this invention does not involve complex mathematical calculations and data processing, making it user-friendly and facilitating the market promotion of this invention.

[0090] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A single-particle elemental and isotopic analysis system, characterized in that: The system includes: Mass spectrometer, high-speed ion counting detector, high-speed oscilloscope and data processing system; The mass spectrometer and the high-speed ion counting detector are connected via corresponding connecting lines; The high-speed ion counting detector is connected to the high-speed oscilloscope via corresponding connecting lines; The high-speed oscilloscope is connected to the data processing system via corresponding connection cables; The mass spectrometer is equipped with: a nebulizer injection system, an ICP ionization system, and a mass analyzer. The suspension or colloidal solution of particulate matter samples is dispersed into micron-sized droplets encapsulating individual particulate cells by the atomization injection system; The particulate samples include metal-based nanoparticles, natural nanominerals with nano to micron sizes, and samples in the form of single cells as microparticles / droplets. The micron-sized droplets are introduced into the ICP ionization system for ionization, resulting in an ion cluster with sparse edges and a dense center. The mass analyzer is used to screen out ion clusters composed of specific isotopes to obtain the screened ion clusters. The high-speed ion counting detector is used to detect the screened ion clusters transmitted by the mass spectrometer and convert them into the form of current / voltage pulses; The high-speed oscilloscope converts the current / voltage pulses into simplified signals; The data processing system processes the simplified signal to obtain multi-dimensional information, including the particle size and isotope ratio of individual particles, and statistically analyzes a large number of particles in the same batch to obtain statistical results. The high-speed oscilloscope continuously scans the signal output by the high-speed ion counting detector with a dynamic time window of adjustable duration, and displays and stores all data points within the time window when the trigger acquisition conditions are met. The triggering conditions for data collection include: the number of peaks per unit time reaching a preset threshold and the interval between adjacent peaks reaching a preset threshold.

2. The elemental and isotopic analysis system for a single particle as described in claim 1, characterized in that: The specific process by which the data processing system processes the simplified signal is as follows: The data processing system first converts single-particle events into a cumulative count graph that changes over time; Multidimensional information, including the particle size and isotope ratio of individual particles, can be directly obtained from the cumulative count plot that changes over time.

3. The elemental and isotopic analysis system for a single particle as described in claim 1, characterized in that: The duration of the dynamic time window is 0.4ms to 2ms.

4. A method for elemental and isotopic analysis of a single particle, applied to the elemental and isotopic analysis system for a single particle as described in any one of claims 1 to 3, characterized in that: The method includes the following steps: S1. Electrically connect the mass spectrometer to the high-speed ion counter detector; connect the input channel of each high-speed oscilloscope to one detection channel of the high-speed ion counter, and configure the trigger acquisition conditions of the high-speed oscilloscope; S2. The particulate matter sample is processed into a colloidal / suspension, and then atomized using a nebulizer to convert the large volume of liquid into small droplets containing particulate matter, which are then sprayed into an ICP ionization system for ionization. A mass analyzer is used to screen out ion clusters composed of specific isotopes to obtain the screened ion clusters. S3. Based on the trigger acquisition conditions of the high-speed oscilloscope, each high-speed oscilloscope channel collects the electrical signal transmitted by the corresponding high-speed ion counting detector and records the original signal profile generated by the ion clusters after screening within a dynamic time window; the original signal profile is simultaneously converted into a simplified signal by the high-speed oscilloscope. S4. The data processing system statistically simplifies the multi-dimensional information of a single particle in the signal and the statistical information of a large number of particles in the same batch, and outputs the information.

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