Single cell biopsy and dynamic transcriptome tracking system and method
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- XIAMEN UNIV
- Filing Date
- 2026-04-30
- Publication Date
- 2026-07-24
Smart Images
Figure CN122445779A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of single-cell sequencing technology, and in particular to a single-cell biopsy and dynamic transcriptome tracking system and method. Background Technology
[0002] The advent and development of single-cell sequencing technology (scRNA-seq) can reveal hidden cellular subpopulations and their molecular characteristics in complex tissues. However, the core limitation of this technology lies in its "destructive" nature—cells must be lysed to obtain transcriptome information. This "endpoint method" freezes each cell at the moment of death, making it merely a static "time snapshot."
[0003] This limitation leads to two fundamental scientific problems that are difficult to solve: First, it is difficult to distinguish whether the observed differences in cell states are due to the inherent heterogeneity of the cell population or different stages of the same cell in a dynamic life process; second, for core biological processes such as cell fate determination, signal transduction cascade reactions, and cell responses to external stimuli, we can only speculate by comparing the starting point and the ending point in a "black box" manner, and we cannot directly observe their internal dynamic evolution mechanisms.
[0004] To unravel this "black box," the scientific community urgently needs a paradigm shift—from "destructive snapshots" to "non-destructive biopsies." The ideal solution should enable continuous tracking and multiple sampling of the same live cell over time without sacrificing cell viability. This requires not only the technical achievement of trace, non-destructive cytoplasmic extraction but also precise spatial localization at the subcellular scale, thereby capturing the spatiotemporal dynamics of the transcriptome at the whole-genome level.
[0005] The closest existing technologies include the following:
[0006] 1. Traditional high-throughput single-cell sequencing technologies: Mainstream platforms such as 10x Genomics and Smart-seq2 are inherently limited to endpoint-based detection. Once a cell is lysed, its life activities cease, making it impossible to continuously track the same cell and fundamentally eliminating the possibility of studying dynamic cellular processes.
[0007] 2. Live-cell imaging: This technique enables long-term dynamic tracking of live cells, making it a powerful tool for studying cellular dynamics. However, its limitation lies in its typical focus on a few pre-known, fluorescently labeled genes. This method cannot unbiasedly reveal overall changes in the transcriptome at the whole-genome level, and its scope and depth are far inferior to sequencing technology.
[0008] 3. Metabolic marker-based sequencing methods: To overcome the limitations of cell inactivation, some novel strategies utilize metabolic markers to "timestamp" newly synthesized RNA. While this method cleverly separates the upstream and downstream of the reaction and ensures cell viability, its conversion rate is usually low and the experimental cycle is long. More importantly, these metabolic marker strategies may potentially affect the spatial localization of mRNA, thereby interfering with the study of the fine subcellular spatial distribution within cells and making it difficult to achieve targeted tracking of specific subcellular structures.
[0009] Therefore, current mainstream single-cell time omics analysis methods have significant limitations: they cannot distinguish between the inherent heterogeneity of cell populations and different stages of the same cell in a dynamic process, and they lack integrated single-cell dynamic transcriptome biopsy systems. Summary of the Invention
[0010] The purpose of this invention is to solve the above-mentioned problems in the prior art and provide a single-cell biopsy and dynamic transcriptome tracking system and method, which can perform low-damage multiple longitudinal biopsies on the same single live cell, and combine downstream sequencing to construct a dynamic transcriptome atlas of a single cell on the time axis.
[0011] To achieve the above objectives, the present invention adopts the following technical solution:
[0012] A single-cell biopsy and dynamic transcriptome tracking method includes the following steps:
[0013] 1) Place the single cell to be tested in a cell culture dish and culture it;
[0014] 2) The single cell is punctured using a quartz nanocapillary to extract a trace amount of cytoplasm sample, the volume of which does not exceed 10% of the total volume of the single cell; wherein the tip diameter of the quartz nanocapillary is 100~1000nm and its surface is modified with amino grouping.
[0015] 3) Allow the single cells to recover in the culture environment;
[0016] 4) Apply specific stimulation to the recovered single cells;
[0017] 5) At one or more time points after the application of stimulation, the same single cell is punctured again using a quartz nanocapillary and a small amount of cytoplasmic sample is extracted, and the single cell is restored after each extraction.
[0018] 6) Reverse transcription, amplification, library construction, and sequencing were performed on cytoplasmic samples extracted at each time point to obtain dynamic transcriptome data of the single cell at different time points.
[0019] The amination modification is APTES modification.
[0020] In this invention, the volume of cytoplasm extracted each time is 0.16~5pL.
[0021] The specific stimulus is glucose stimulation, which is achieved by adding a culture medium containing 1-5 mM glucose to the cell culture dish.
[0022] In this invention, after each extraction, the environment around the single cell is cleaned by replacing the culture medium in the cell culture dish, and the culture medium is restored to normal.
[0023] The library preparation method is either the Smart-seq2 single-cell whole transcription library preparation method, the 10x Genomics single-cell library preparation method, or a targeted sequencing panel.
[0024] The sequencing was performed using a high-throughput sequencing platform.
[0025] A single-cell biopsy and dynamic transcriptome tracking system for the method, comprising:
[0026] The mechanical positioning module includes an inverted optical microscope, a micromanipulator, and a capillary holder. The micromanipulator is fixed to the edge of the stage of the inverted optical microscope via a G-clamp. The capillary holder is mounted on the micromanipulator and is used to hold the quartz nanocapillaries. The capillary holder is located within the working distance below the objective lens of the inverted optical microscope, so that the tip of the quartz nanocapillary is in the same focal plane as the cells in the cell culture dish.
[0027] An electrochemical extraction circuit includes a working electrode, a reference / counter electrode, and an intelligent control module. The working electrode is made of conductive silver wire, placed inside the quartz nanocapillary, and connected to the working electrode interface of the intelligent control module via a wire. The reference / counter electrode is made of another conductive silver wire, inserted into the buffer solution of the cell culture dish, and connected to the reference / counter electrode interface of the intelligent control module via a wire. When the tip of the quartz nanocapillary is immersed in the buffer solution and penetrates into the cytoplasm, the working electrode, the capillary fluid, the cytoplasm, the buffer solution, and the reference / counter electrode together constitute a series electrolytic cell circuit.
[0028] The intelligent control module includes a microcontroller, a Bluetooth module, a relay, an adjustable power supply, and a real-time circuit monitoring unit. The microcontroller communicates wirelessly with a mobile terminal via the Bluetooth module to receive user-defined extraction parameters. The output of the microcontroller is connected to the relay to control its closing duration. The relay is connected in series between the adjustable power supply and the reference / counter electrode. The real-time circuit monitoring unit is connected to the working electrode and the reference / counter electrode via a standard resistor to collect the loop impedance in real time and feed it back to the microcontroller.
[0029] The power supply module provides operating power to the microcontroller and the real-time circuit monitoring unit.
[0030] The microcontroller is an Arduino Nano, the Bluetooth module is an HC-06 low-power Bluetooth module, and the relay is a JOC-3FF-SZ relay.
[0031] The micromanipulator includes an XYZ coarse adjustment positioning and fixing device and an XYZ fine adjustment controller, wherein the resolution of the fine adjustment controller is ≤10μm.
[0032] Compared with the prior art, the beneficial effects achieved by the technical solution of this invention are:
[0033] 1. Dynamic Tracking Capability: Existing single-cell sequencing technologies cannot capture continuous changes in cells over time, making it impossible to analyze the continuous response process of cells to stimuli (such as drugs and glucose metabolism). This invention breaks through the static limitations of traditional single-cell sequencing, achieving "movie-level" dynamic observation of the entire genome of a single cell, and is able to analyze the continuous changes in cell fate.
[0034] 2. High biocompatibility and low damage: Traditional handmade glass microneedles are typically large in diameter (micrometers) and have rough surfaces, which can easily lead to cell death or trigger non-specific stress responses during the puncture process, affecting the accuracy of subsequent dynamic data. Compared with traditional handmade glass microneedles, this invention uses quartz nanocapillaries modified with APTES, which significantly reduces mechanical damage and biochemical stress to cells during puncture, ensuring high cell survival rate and physiological activity after biopsy.
[0035] 3. Standardization and Automation: Existing single-cell biopsies are mostly performed manually, resulting in poor reproducibility and difficulty in achieving high throughput and automation. This invention standardizes complex single-cell operations through an integrated hardware and software control system, lowering the technical threshold and improving experimental reproducibility and throughput. Attached Figure Description
[0036] Figure 1 This is a structural block diagram of the present invention.
[0037] Figure 2 This is a physical structural diagram of the system of the present invention.
[0038] Figure 3 This is a comparison diagram between traditional single-cell sequencing and the dynamic tracking method of this invention.
[0039] Figure 4 To illustrate the association between the calcium oscillation phenotype and genotype, we present the relative fluorescence intensity-time relationship diagram and the calcium oscillation gene correlation-gene sequence diagram within 90 minutes for different cells. Detailed Implementation
[0040] To make the technical problems, technical solutions and beneficial effects of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments.
[0041] Example 1
[0042] Figure 1 and Figure 2 The actual layout of the circuit hardware and mechanical structure of the present invention is presented, which intuitively demonstrates the physical connection and collaborative working method of each functional module.
[0043] like Figure 2 As shown in the physical diagram, the system comprises an intelligent control module (left) and a mechanical positioning module (right). The intelligent control module is built on a general-purpose circuit board, with an Arduino Nano microcontroller at its core. It integrates an HC-06 low-power Bluetooth module for wireless communication, a JOC-3FF-SZ relay module as an electronic switch, and an adjustable power supply module to provide a stable driving voltage. A real-time monitoring circuit is formed through the working electrode, reference / counter electrode, and a standard resistor. The mechanical positioning module employs a multi-level adjustment structure: an XYZ coarse-tuning positioning fixture enables large-range three-dimensional movement; an XYZ fine-tuning controller (10μm resolution) achieves subcellular-level precise alignment; a capillary holder securely fixes the quartz nanocapillary; and a G-clamp firmly mounts the device to the edge of the inverted optical microscope stage, compatible with most microscope models. During operation, the user sets the volume via software, and the signal is transmitted to the microcontroller via Bluetooth. This controls the relay to close and connect the electrode circuit, generating an electric field at the tip of the quartz nanocapillary to drive the cell into the tube. Simultaneously, the microcontroller monitors the circuit status in real time through a standard resistor, achieving fully intelligent operation from macroscopic mechanical positioning to microscopic electronic extraction.
[0044] Specifically, the single-cell biopsy and dynamic transcriptome tracking system described in this embodiment is built on an inverted optical microscope platform. Through the coordinated operation of a mechanical positioning module and an electro-controlled extraction module, it achieves non-destructive continuous sampling of live cells. The specific structural composition, connection relationships, and working principle of the system are as follows:
[0045] Mechanical Positioning Module: The main mechanical components of the system consist of a micromanipulator and an inverted optical microscope. The micromanipulator is rigidly fixed to the edge of the microscope stage using G-clamps, ensuring no relative displacement during operation. The micromanipulator is equipped with a capillary holder for securely holding the quartz nanocapillaries. Spatially, the capillary holder is positioned within the working distance below the microscope objective, ensuring that the tips of the quartz nanocapillaries and the culture dish on the stage are on the same focal plane, facilitating real-time observation of the relative position of the quartz nanocapillaries and cells through the microscope.
[0046] Construction of the electrochemical extraction circuit: The core extraction function of the system relies on a closed electrochemical circuit, and its connection method is as follows:
[0047] Working electrode (cathode): A section of conductive silver wire is placed inside a quartz nanocapillary. This silver wire is connected to the working electrode interface (i.e., the negative output terminal of the control box) in the aforementioned intelligent control module via a wire.
[0048] Reference / counter electrode (anode): A separate conductive silver wire is used, which is directly inserted into the culture dish containing the cells (buffer solution). This silver wire is connected to the reference / counter electrode interface of the intelligent control module (i.e., the positive output terminal of the control box) via a wire.
[0049] Circuit formation: When the tip of the quartz nanocapillary is immersed in the solution in the culture dish, the solution inside the quartz nanocapillary becomes conductive with the solution in the culture dish. At this point, the working electrode, the liquid inside the capillary, the cytoplasm, the liquid inside the culture dish, and the reference / counter electrode together form a series electrolytic cell circuit.
[0050] like Figure 1 As shown in the block diagram, the main functions of this invention include intelligent control and biopsy monitoring, which are coordinated and processed by a microcontroller. The specific workflow of the system is as follows:
[0051] First, during the user interaction and command generation phase, the system is equipped with a user interface to receive the target extraction volume set by the user. This volume signal is input to an embedded extraction volume-power-time conversion module, which has a built-in conversion algorithm to map the extraction volume to the corresponding power-time parameter. Subsequently, this power-time parameter is wirelessly transmitted to the microcontroller via Bluetooth Low Energy.
[0052] Secondly, during the control execution phase, the microcontroller, based on the received power-on time command, outputs a control signal through its RTX port to drive the relay. The relay, acting as a switching element, is connected in series between the adjustable power supply and the reference / counter electrode. Specifically, the adjustable power supply outputs a drive voltage; when the relay is closed, this voltage is applied to the reference / counter electrode; simultaneously, the working electrode in the system is grounded. By precisely controlling the relay's closing duration, precise timing control of the voltage applied across the electrodes is achieved, thereby driving the electrochemical reaction for single-cell extraction.
[0053] Finally, in the real-time feedback and monitoring phase, the system integrates a real-time circuit monitoring loop. This loop consists of a standard resistor, a working electrode, and a reference / counter electrode forming a series circuit. The real-time circuit monitoring module detects the voltage across the standard resistor, calculates the loop impedance change in real time using the voltage divider principle, and feeds this monitoring data back to the microcontroller. This design enables the system to monitor the circuit status in real time during the extraction process, ensuring the stability and safety of the extraction process. Furthermore, the power supply module provides a stable operating power supply for the microcontroller and monitoring module.
[0054] This invention utilizes the electroosmotic effect to achieve precise extraction of single-cell contents and combines it with mechanical displacement to achieve dynamic tracking. The specific operation process is as follows:
[0055] 1. Positioning and puncture: Using a microscope to observe the target cells, the displacement system (coarse and fine adjustment) of the micromanipulator is adjusted to control the movement of the quartz nanocapillary tip to the surface of the target cells, and a mechanical puncture action is performed to allow the quartz nanocapillary tip to enter the cytoplasm.
[0056] 2. Electrostatic Extraction: Upon activation of the intelligent control module, the system applies a DC bias voltage between the working electrode and the reference / counter electrode according to preset extraction parameters (such as voltage value and energizing time). Since the capillary wall is typically negatively charged, under the influence of the electric field, cations in the solution move towards the cathode (inside the capillary), causing solvent molecules to generate electroosmotic flow. This hydrodynamic process draws mRNA and cytoplasmic components from the cytoplasm into the quartz nanocapillary.
[0057] 3. Dynamic Longitudinal Tracking: After extraction, the voltage is removed, and the quartz nanocapillary is retracted. Due to the non-destructive extraction method, the cells remain viable. After the cells recover in normal culture medium, a specific stimulus is applied to the single cell (e.g., changing to a culture medium containing a low concentration of glucose). At one or more set time points after the stimulus (e.g., 0.5 h, 2.5 h), the displacement system is used again to locate the same cell, and the above puncture and electro-controlled extraction steps are repeated. After each extraction, the cell is allowed to recover, thereby obtaining cytoplasmic samples of the single cell along a continuous time axis before and after stimulation.
[0058] By combining the above-described structure and method, this system can continuously acquire cytoplasmic samples at different time points of the same cell, thereby achieving... Figure 3 The right side shows a single-cell longitudinal dynamic transcriptome tracing.
[0059] Figure 3 By comparing the experimental procedures, the fundamental differences between traditional single-cell sequencing (left) and the method of this invention (right) in analyzing the dynamic evolution of cells are intuitively demonstrated.
[0060] like Figure 3As shown on the left, traditional single-cell sequencing (scRNA-seq) follows a “destructive snapshot” strategy.
[0061] To construct an experiment with three time points (0h, 0.5h, and 2.5h) and three biological replicates at each time point, researchers must use nine independent cells. At each time point, the cells are lysed to extract their complete RNA for sequencing. The implicit assumption of this method is that cells at different time points are strictly comparable in genotype and physiological state. However, due to the pervasive heterogeneity among single cells, this data splicing based on different cells essentially records the static states of multiple cells discretely, rather than continuously observing the true evolutionary trajectory of the same cell. This necessitates relying on statistical algorithms such as pseudo-time for "smoothing interpolation" when reconstructing cell developmental trajectories, which may fabricate biologically non-existent intermediate states or incorrectly connect irrelevant cell lineages.
[0062] like Figure 3 As shown on the right, this invention uses non-destructive quartz nanocapillary biopsy technology to achieve longitudinal dynamic tracking of single cells.
[0063] In this method, researchers only need three live cells to continuously and minutely extract cytoplasm from the same cell at different time points (0h, 0.5h, 2.5h) using quartz nanocapillaries. Because the cells remain viable, the entire process is a direct record of the true state of the same cell across a continuous timeline. This method not only significantly reduces the number of cells required for experiments, but more importantly, it fully preserves the unique dynamic information of each cell, such as the oscillation frequency of gene expression, the temporal shift of peak occurrences, and the phase difference relationships between multiple genes. Through direct observation, this invention establishes a direct causal chain between cell state evolutions, effectively solving the core problem that traditional methods cannot overcome due to "time trajectory breaks."
[0064] Example 2: Dynamic tracking of glucose response in αTC1-6 cells based on the Smart-Biop-seq platform
[0065] I. Preparation of Quartz Nanocapillaries
[0066] Drawing: Using a laser drawing instrument, quartz capillaries are drawn into nanoneedles with a tip diameter of about 500 nm.
[0067] Amination modification via APTES: The drawn quartz nanocapillaries were immersed in a 5% APTES solution for 30 minutes, and then dried and cured at 150°C to impart aminated hydrophilic groups to the tip surface, thereby preparing quartz nanocapillaries (qNMC) with smooth surface, good biocompatibility and moderate rigidity.
[0068] II. Cell Culture and Hardware Preparation
[0069] Cells: αTC1-6 cells were seeded in cell culture dishes and cultured until they adhered to the culture vessel.
[0070] System: Launch the integrated control APP, connect the micromanipulator and the embedded motion controller, and calibrate the zero position of the quartz nanocapillary.
[0071] III. Gradient glucose stimulation and longitudinal biopsy
[0072] Baseline acquisition (T0): Using the APP to control the quartz nanocapillary to puncture a single cell, about 2 pL of cytoplasm was extracted (denoted as Sample-T0), and the cell remained viable.
[0073] Stimulation: The culture medium in the petri dish was replaced with a solution containing 1 mM glucose.
[0074] Dynamic sampling (T1 / T2): The same cell was punctured and cytoplasm was extracted again at 30 minutes (T1) and 60 minutes (T2) after stimulation (Sample-T1, Sample-T2).
[0075] Cleaning and recovery: After each extraction, the environment is cleaned by changing the solution in the culture dish to ensure that the cells are in normal culture medium to recover.
[0076] IV. Transcription, Library Construction, and Sequencing
[0077] The cytoplasmic samples extracted three times were subjected to reverse transcription (RT) and PCR amplification, respectively.
[0078] Sequencing libraries were constructed and sequenced using Illumina NovaSeq.
[0079] This invention successfully obtained dynamic gene curves of a single cell under low glucose stimulation, correlated with glucagon time, demonstrating the effectiveness of the dynamic transcriptome tracking method. Specifically, in order to accurately identify key effector molecules driving the high-secretion phenotype of single cells from a massive gene pool, this invention utilizes this system to construct a multidimensional association analysis framework of "functional phenotype-transcriptome".
[0080] like Figure 4 As shown in the left figure, the 15 lines represent 15 cells, and the vertical axis represents fluorescence intensity (indicating calcium oscillations, corresponding to glucagon secretion). This invention first used the Fluo-4 probe to monitor the intracellular calcium ion concentration ([Ca ions]) in 15 single cells in real time. 2+The dynamic trajectory of glucagon secretion was analyzed, and the slope of calcium signal change at 0.5 h was used as a direct proxy indicator for glucagon secretion activity. Subsequently, this functional parameter was subjected to Pearson correlation analysis with single-cell dynamic transcriptome data acquired by the system of this invention. Correlation map ( Figure 4 The right-hand figure shows that the expression levels of certain genes (such as Cox8a) are strongly positively correlated with calcium signal intensity, while most genes show no significant correlation. This result not only successfully achieves precise focusing from massive sequencing data to a single core target, but also statistically establishes the status of key genes as the hub connecting metabolic reprogramming and secretion execution, fully validating the practical value of this system in analyzing the dynamic evolution process and physiological response mechanism of single cells.
Claims
1. A method for single-cell biopsy and dynamic transcriptome tracking, characterized in that, Includes the following steps: 1) Place the single cell to be tested in a cell culture dish and culture it; 2) The single cell is punctured using a quartz nanocapillary to extract a trace amount of cytoplasm sample, the volume of which does not exceed 10% of the total volume of the single cell; wherein the tip diameter of the quartz nanocapillary is 100~1000nm and its surface is modified with amino grouping. 3) Allow the single cells to recover in the culture environment; 4) Apply specific stimulation to the recovered single cells; 5) At one or more time points after the application of stimulation, the same single cell was punctured again using a quartz nanocapillary and a small amount of cytoplasmic sample was extracted, with the single cell being restored after each extraction. 6) Reverse transcription, amplification, library construction, and sequencing were performed on cytoplasmic samples extracted at each time point to obtain dynamic transcriptome data of the single cell at different time points.
2. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: The amination modification is APTES modification.
3. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: The volume of cytoplasm extracted each time is 0.16~5pL.
4. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: The specific stimulus is glucose stimulation, which is achieved by adding a culture medium containing 1-5 mM glucose to the cell culture dish.
5. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: After each extraction, the environment around the single cell is cleaned by changing the culture medium in the cell culture dish, and the culture medium is restored to normal.
6. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: The library preparation method is either the Smart-seq2 single-cell whole transcription library preparation method, the 10x Genomics single-cell library preparation method, or a targeted sequencing panel.
7. The single-cell biopsy and dynamic transcriptome tracking method as described in claim 1, characterized in that: The sequencing was performed using a high-throughput sequencing platform.
8. A single-cell biopsy and dynamic transcriptome tracking system for use in the method of any one of claims 1 to 7, characterized in that, include: The mechanical positioning module includes an inverted optical microscope, a micromanipulator, and a capillary holder. The micromanipulator is fixed to the edge of the stage of the inverted optical microscope via a G-clamp. The capillary holder is mounted on the micromanipulator and is used to hold the quartz nanocapillaries. The capillary holder is located within the working distance below the objective lens of the inverted optical microscope, so that the tip of the quartz nanocapillary is in the same focal plane as the cells in the cell culture dish. An electrochemical extraction circuit includes a working electrode, a reference / counter electrode, and an intelligent control module. The working electrode is made of conductive silver wire, placed inside the quartz nanocapillary, and connected to the working electrode interface of the intelligent control module via a wire. The reference / counter electrode is made of another conductive silver wire, inserted into the buffer solution of the cell culture dish, and connected to the reference / counter electrode interface of the intelligent control module via a wire. When the tip of the quartz nanocapillary is immersed in the buffer solution and penetrates into the cytoplasm, the working electrode, the capillary fluid, the cytoplasm, the buffer solution, and the reference / counter electrode together constitute a series electrolytic cell circuit. The intelligent control module includes a microcontroller, a Bluetooth module, a relay, an adjustable power supply, and a real-time circuit monitoring unit; the microcontroller communicates wirelessly with the mobile terminal via the Bluetooth module to receive user-defined extraction parameters; the output of the microcontroller is connected to the relay to control the relay's closing duration. The relay is connected in series between the adjustable power supply and the reference / counter electrode; the real-time circuit monitoring unit is connected to the working electrode and the reference / counter electrode through a standard resistor, and collects the loop impedance in real time and feeds it back to the microcontroller; The power supply module provides operating power to the microcontroller and the real-time circuit monitoring unit.
9. The single-cell biopsy and dynamic transcriptome tracking system as described in claim 8, characterized in that: The microcontroller is an Arduino Nano, the Bluetooth module is an HC-06 low-power Bluetooth module, and the relay is a JOC-3FF-SZ relay.
10. The single-cell biopsy and dynamic transcriptome tracking system as described in claim 8, characterized in that: The micromanipulator includes an XYZ coarse adjustment positioning and fixing device and an XYZ fine adjustment controller, wherein the resolution of the fine adjustment controller is ≤10μm.