CN114361007B - Multidimensional regulating device for single-cell efficient ionization - Google Patents
Multidimensional regulating device for single-cell efficient ionization Download PDFInfo
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- CN114361007B CN114361007B CN202011092157.3A CN202011092157A CN114361007B CN 114361007 B CN114361007 B CN 114361007B CN 202011092157 A CN202011092157 A CN 202011092157A CN 114361007 B CN114361007 B CN 114361007B
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Abstract
The invention provides a multidimensional regulating device for single-cell efficient ionization. The invention relates to a sampling mechanism and a multidimensional adjustment displacement platform for adjusting the space pose of the sampling mechanism, wherein the sampling mechanism comprises an ionization picoliter sampling spray needle for extracting tissue fluid in cells and an electrode plate for providing ionization voltage, a preset distance exists between the ionization picoliter sampling spray needle and the electrode plate, the multidimensional adjustment displacement platform comprises a multidimensional large-step adjusting mechanism and a multidimensional fine adjusting mechanism, the multidimensional large-step adjusting mechanism is used for adjusting the distance between the ionization picoliter sampling spray needle and a quality detecting mechanism, and the multidimensional fine adjusting mechanism is used for adjusting the relative position relation between the spray needle and the electrode plate. According to the invention, by means of two regulation modes of precise regulation and large-step regulation, the regulation range is wide, and simultaneously, for mass spectrum sampling, the regulation range of microns is adopted, so that the sampling needle point can be accurately aligned with the position of the mass spectrum sampling nozzle.
Description
Technical Field
The invention relates to the technical field of single-cell measurement, in particular to a multidimensional regulating device for single-cell efficient ionization.
Background
Single cell analysis is of great interest because it can provide important information for disease detection, gene sequencing, and cell metabonomics. The full-automatic single-cell mass spectrum sample injector with the bulletin number of CN110197786A can be used with various mass spectrometers by extracting single-cell substances such as cytoplasm, cell nucleus and the like and then automatically sending the single-cell substances to a sample inlet of the mass spectrometer for component analysis, wherein the sample needle has wide adjustable distance and height range and can be used with various mass spectrometers, but has great operation difficulty in the sampling process. Meanwhile, in the process of sampling the needle point, the sampling needle point cannot be aligned with the sampling end of the mass spectrum. The in-situ single-cell in-situ lysis and on-line ionization detection mass spectrum interface device with the bulletin number of CN 107863286A adjusts target cells to be right below a microfluidic probe through an electric control objective table, integrates in-situ cell lysis, continuous flow control of lysate and driving of cell lysis component liquid, performs on-line real-time ionization and detection, can perform in-situ fixed-point treatment on cells on adherent cells or tissue slices cultured in a culture dish, realizes in-situ mass spectrum detection, and realizes in-situ full-component analysis on single cells. The utility model discloses a single-cell mass spectrum analyzer with a sample feeding system and a flow focusing device, which has the advantages of large sample flux and high analysis speed, can reduce cell loss in sample feeding and can improve the transmission efficiency of cell particles, and the publication number CN110333282A discloses a single-cell mass spectrum analyzer with a flow sample feeding mode and a flow focusing mode.
The existing single cell online analysis method mainly emphasizes the operation of continuous single cells. Emphasis on continuous sampling process in single cell analysis process, lack of operation of sampling single cell, in situ needle tip. In the prior art, the position of the picoliter sampling needle is not regulated, usually only 2-3 dimensions are needed, the manual operation or the precision is too low, and the position of a single cell is not regulated in the continuous sampling process. The ionization source for single cell operation is located at a distance from the sample inlet and is different in size, resulting in low ionization efficiency.
Disclosure of Invention
According to the technical problem, a multidimensional regulating device for single-cell efficient ionization is provided. The invention adopts the following technical means:
The multidimensional adjusting displacement platform comprises a sample injection mechanism and a multidimensional adjusting displacement platform for adjusting the space pose of the sample injection mechanism, wherein the sample injection mechanism comprises an ionization picoliter sample injection needle for extracting tissue fluid in cells and an electrode plate for providing ionization voltage, a preset distance exists between the ionization picoliter sample injection needle and the electrode plate, the multidimensional adjusting displacement platform comprises a multidimensional large-step adjusting mechanism and a multidimensional fine adjusting mechanism, the multidimensional large-step adjusting mechanism is used for adjusting the distance between the ionization picoliter sample injection needle and a quality detecting mechanism, and the multidimensional fine adjusting mechanism is used for adjusting the relative position relation between the needle and the electrode plate.
Further, the multidimensional large-stride adjusting mechanism comprises a head connecting piece and a plurality of supporting legs connected with the head connecting piece, the head connecting piece is connected with the bottom end of the multidimensional fine adjusting mechanism, and the bottoms of the supporting legs are connected through connecting rods.
Further, the top end of the head connecting piece is provided with a guide rail type structure, and the multidimensional fine adjusting mechanism can slide on the guide rail type structure, so that the position adjustment of the large stride is performed.
Further, the multidimensional fine adjustment mechanism comprises a three-dimensional adjustment base and a needle tip clamping mechanism located on the three-dimensional adjustment base, the three-dimensional adjustment base is installed on the multidimensional large-step adjustment mechanism, the three-dimensional adjustment base can conduct X-axis adjustment, Y-axis adjustment and Z-axis adjustment on the needle tip clamping mechanism, further, the space position of an ionization picoliter sample injection needle installed on the needle tip clamping mechanism can be adjusted, the needle tip clamping mechanism can adjust the pitching angle and the deflection angle of the ionization picoliter sample injection needle, the relative position relation between the ionization picoliter sample injection needle and an electrode slice is changed, and the electrode slice can conduct high-pressure transmission to ionize a single cell sample in the ionization picoliter sample injection needle.
Further, the electrode plate is electrified to be a direct-current high voltage or a high voltage with a sine wave, the range of the direct-current high voltage is 2-5 kV, and the frequency of the high voltage with the sine wave is 0.1-1 kHz.
The invention has the following advantages:
1. The adjusting modes of combining precise adjustment and large-step adjustment are designed, so that the adjusting modes of the picoliter sample injection needle and the mass detector under different environments are adjusted in a wider range by adopting the large-step adjustment under the condition of long distance. The design is added with a high-precision adjusting fine adjusting structure, so that mass spectrum injection can be realized, a micrometer adjusting and controlling range is adopted, and the injection needle point can be accurately aligned with the position of the mass spectrum injection nozzle.
2. The fine adjustment structure can be adjusted in X axis, Y axis, Z axis, angle adjustment of pitching and deflection, and all-round adjustment of five dimensions is done, avoids sampling needle point because the uncontrollable that the adjustment position caused, will adjust the precision and realize micron-order precision, change the distance wantonly, adjust ionization intensity.
3. The high-voltage electrode plate is close to the sampling needle but does not contact with the sampling needle, so that the discharge wire is prevented from contacting the inside of the sampling needle tip, and pollution to a single-cell sample is avoided. The needle tip is placed at the bottom end of the sample injection needle and is close to the sample injection needle, so that the needle tip can be conveniently discarded. Meanwhile, the position of the discharge electrode plate is close to the needle point, so that high voltage can be transmitted, and single cell samples in the sample injection needle can be ionized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to the drawings without inventive effort to a person skilled in the art.
FIG. 1 is a schematic diagram of the overall structure of the present invention.
Fig. 2 is a front view of the present invention.
Fig. 3 is a right side view of the present invention.
Fig. 4 is a top view of the present invention.
Fig. 5 is a simplified schematic of the structure of the present invention connected to a mass spectrometer.
In the figure: 001. a sample injection spray needle; 002. an X-axis fine adjustment mechanism; 003. a Y-axis fine adjustment mechanism; 004. a Z-axis fine adjustment mechanism; 005. a needle tip angle adjustment mechanism; 006. an electrode sheet; 007. a high-pressure support rod; 008. a large stride angle adjustment mechanism; 009. a large stride position adjustment mechanism; 010. connecting a supporting frame; 011. the high-voltage electrode is connected with the supporting frame; 012. a mass spectrum detector; 021. a multi-dimensional large stride adjustment mechanism; 022. a multidimensional fine adjustment mechanism; 023. and a sample feeding mechanism.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
As shown in fig. 1-5, the embodiment discloses a multidimensional adjustment device for single-cell efficient ionization, which comprises a sampling mechanism 023 and a multidimensional adjustment displacement platform for adjusting the space pose of the sampling mechanism, wherein the sampling mechanism comprises an ionization picoliter sampling needle 001 for extracting tissue fluid in cells and an electrode slice 006 for providing ionization voltage, a preset distance exists between the ionization picoliter sampling needle and the electrode slice, the multidimensional adjustment displacement platform comprises a multidimensional large-step adjustment mechanism 021 and a multidimensional fine adjustment mechanism 022, the multidimensional large-step adjustment mechanism is used for adjusting the distance between the ionization picoliter sampling needle and a mass detection mechanism, and the multidimensional fine adjustment mechanism is used for adjusting the relative position relation between the ionization picoliter sampling needle and the electrode slice, in the embodiment, the mass detection mechanism is a mass spectrometer 012.
The multidimensional large-stride adjusting mechanism comprises a head connecting piece and a plurality of supporting legs connected with the head connecting piece, wherein the head connecting piece is connected with the bottom end of the multidimensional fine adjusting mechanism, and the bottoms of the supporting legs are connected through connecting rods. Most big stride adjustment mechanism can accomplish big stride position adjustment function and big stride angle adjustment function, and big stride position adjustment mechanism 009 mainly includes the top of head connecting piece is equipped with the guide tracked structure, the fine adjustment mechanism of multidimension can slide above that, and then carries out the position adjustment of big stride. The large-stride angle adjusting mechanism 008 is mainly formed by a leg structure, and the leg structure on the periphery is connected to the middle leg in a hinged manner, and can be a tripod type bracket.
The lower extreme of advance appearance needle is leaned on the electrode slice, the electrode slice is a sheetmetal, and it is connected with high voltage power supply, and the electrode slice passes through high voltage support pole 007 and high voltage electrode connection support frame 011 to be connected on the base of multidimensional fine adjustment mechanism. And applying high pressure on the metal sheet to form ion flow at the position of the injection needle. The electrode plate is electrified to be direct-current high voltage or high voltage with sine wave, the range of the direct-current high voltage is 2-5 kV, and the frequency of the high voltage with sine wave is 0.1-1 kHz.
The multi-dimensional fine adjustment mechanism comprises a three-dimensional adjustment base and a needle point clamping mechanism which is located on the three-dimensional fine adjustment base through a connecting support frame 010, the three-dimensional adjustment base is installed on the multi-dimensional large-step adjustment mechanism, the three-dimensional adjustment base can conduct X-axis adjustment, Y-axis adjustment and Z-axis adjustment on the needle point clamping mechanism through the X-axis fine adjustment mechanism 002, the Y-axis fine adjustment mechanism 003 and the Z-axis fine adjustment mechanism 004, further the space position of an ionization picoliter sample injection needle installed on the needle point clamping mechanism can be adjusted, the needle point clamping mechanism can conduct adjustment on the pitching angle and the deflection angle of the ionization picoliter sample injection needle through the needle point angle adjustment mechanism 005, so that the relative position relation between the ionization picoliter sample injection needle and an electrode slice is changed, the electrode slice can conduct high-pressure transmission to ionize single cell samples in the ionization picoliter sample injection needle, the electrode slice position and the needle point distance are kept fixed, the high-voltage electrode slice can conduct fine adjustment on the needle point position, the ionization picoliter sample injection needle point can be contacted with the sample, and ionization efficiency is effectively increased, and ionization efficiency is reduced. The invention can effectively and finely adjust the position of the picoliter sample injection needle, control the ionization efficiency and improve the high-efficiency ionization of single cells.
In this embodiment, the needle tip clamping mechanism includes a main frame body and a screwing/loosening mechanism disposed on the main frame body, the root of the needle tip is fixed on a cylindrical fixing portion, the screwing/loosening mechanism is used for fixing the cylindrical fixing portion, and the screwing/loosening mechanism can be fixed by using a screw with low manufacturing cost, or a stably clamped claw, or a mechanism suitable for detaching or fixing the needle tip at any time, such as electric control. When the claw is selected, the embodiment is also matched with a corresponding clamp, and after the needle point is clamped by the clamp, the claw clamps the clamp, so that the needle point is fixed. The needle point clamping mechanism is internally provided with a rolling device, and the pitching angle and the deflection angle of the sample injection needle are adjusted through the rolling device.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (3)
1. The multidimensional adjusting device for single-cell efficient ionization is characterized by comprising a sample injection mechanism and a multidimensional adjusting displacement platform for adjusting the space pose of the sample injection mechanism, wherein the sample injection mechanism comprises an ionization picoliter sample injection needle for extracting tissue fluid in cells and an electrode plate for providing ionization voltage, a preset distance exists between the ionization picoliter sample injection needle and the electrode plate, the multidimensional adjusting displacement platform comprises a multidimensional large-step adjusting mechanism and a multidimensional fine adjusting mechanism, the multidimensional large-step adjusting mechanism is used for adjusting the distance between the ionization picoliter sample injection needle and a quality detecting mechanism, and the multidimensional fine adjusting mechanism is used for adjusting the relative position relation between the ionization picoliter sample injection needle and the electrode plate;
The multi-dimensional large-stride adjusting mechanism comprises a head connecting piece and a plurality of supporting legs connected with the head connecting piece, wherein the head connecting piece is connected with the bottom end of the multi-dimensional fine adjusting mechanism, and the bottoms of the supporting legs are connected through connecting rods;
The multi-dimensional fine adjusting mechanism comprises a three-dimensional adjusting base and a needle tip clamping mechanism located on the three-dimensional adjusting base, the three-dimensional adjusting base is installed on the multi-dimensional large-step adjusting mechanism, the three-dimensional adjusting base can conduct X-axis adjustment, Y-axis adjustment and Z-axis adjustment on the needle tip clamping mechanism, further, the space position of an ionization picoliter sample injection needle installed on the needle tip clamping mechanism can be adjusted, the needle tip clamping mechanism can adjust the pitching angle and the deflection angle of the ionization picoliter sample injection needle, the relative position relation between the ionization picoliter sample injection needle and an electrode slice is changed, and the electrode slice can conduct high-pressure transmission to ionize a single cell sample in the ionization picoliter sample injection needle.
2. The multi-dimensional adjusting device for single-cell high-efficiency ionization according to claim 1, wherein a guide rail structure is provided at the top end of the head connector, and the multi-dimensional fine adjusting mechanism can slide thereon to perform a large-stride position adjustment.
3. The multidimensional regulating device for efficient single-cell ionization according to claim 1 or 2, wherein the electrode pad is energized to a high voltage of direct current or a high voltage with sine wave, the high voltage of direct current ranges from 2 to 5 kV, and the high voltage frequency with sine wave ranges from 0.1 to 1 kHz.
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| CN202011092157.3A CN114361007B (en) | 2020-10-13 | 2020-10-13 | Multidimensional regulating device for single-cell efficient ionization |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103972019A (en) * | 2014-05-12 | 2014-08-06 | 清华大学 | Non-contact direct-current induction electrospray ionization device and method |
| CN209587579U (en) * | 2019-01-24 | 2019-11-05 | 李建刚 | A kind of adjustment structure for height of leveling instrument |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6495823B1 (en) * | 1999-07-21 | 2002-12-17 | The Charles Stark Draper Laboratory, Inc. | Micromachined field asymmetric ion mobility filter and detection system |
| US7405396B2 (en) * | 2005-05-13 | 2008-07-29 | Applera Corporation | Sample handling mechanisms and methods for mass spectrometry |
| US8901487B2 (en) * | 2007-07-20 | 2014-12-02 | George Washington University | Subcellular analysis by laser ablation electrospray ionization mass spectrometry |
| WO2011139274A1 (en) * | 2010-05-05 | 2011-11-10 | George Washington University | Methods for detecting metabolic states by laser ablation electrospray ionization mass spectrometry |
| WO2012024468A2 (en) * | 2010-08-19 | 2012-02-23 | Leco Corporation | Time-of-flight mass spectrometer with accumulating electron impact ion source |
| JP6554681B2 (en) * | 2014-06-02 | 2019-08-07 | 株式会社Humanix | Nanospray ionization / High performance chip |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103972019A (en) * | 2014-05-12 | 2014-08-06 | 清华大学 | Non-contact direct-current induction electrospray ionization device and method |
| CN209587579U (en) * | 2019-01-24 | 2019-11-05 | 李建刚 | A kind of adjustment structure for height of leveling instrument |
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