CN114361007A - Multidimensional adjusting device for efficient ionization of single cells - Google Patents
Multidimensional adjusting device for efficient ionization of single cells Download PDFInfo
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- CN114361007A CN114361007A CN202011092157.3A CN202011092157A CN114361007A CN 114361007 A CN114361007 A CN 114361007A CN 202011092157 A CN202011092157 A CN 202011092157A CN 114361007 A CN114361007 A CN 114361007A
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- 230000007246 mechanism Effects 0.000 claims abstract description 81
- 239000007921 spray Substances 0.000 claims abstract description 21
- 238000001514 detection method Methods 0.000 claims abstract description 9
- 238000006073 displacement reaction Methods 0.000 claims abstract description 8
- 238000002347 injection Methods 0.000 claims description 20
- 239000007924 injection Substances 0.000 claims description 20
- 230000003834 intracellular effect Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 230000003750 conditioning effect Effects 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 238000005070 sampling Methods 0.000 abstract description 23
- 238000001819 mass spectrum Methods 0.000 abstract description 6
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- 239000000523 sample Substances 0.000 description 32
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- 238000011065 in-situ storage Methods 0.000 description 6
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Abstract
The invention provides a multidimensional adjusting device for efficient ionization of single cells. The invention relates to a sample feeding mechanism and a multidimensional adjustment displacement platform for adjusting the spatial pose of the sample feeding mechanism, wherein the sample feeding mechanism comprises an ionization skin-liter sample feeding spray needle for extracting tissue fluid in cells and an electrode plate for providing ionization voltage, a preset distance is reserved between the ionization skin-liter sample feeding 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 skin-liter sample feeding spray needle and a quality detection mechanism, and the multidimensional fine adjusting mechanism is used for adjusting the relative position relation between the spray needle and the electrode plate. The invention combines the two adjusting modes of precise adjustment and large-step adjustment, has wide adjusting range, and simultaneously adopts micron adjusting range aiming at mass spectrum sampling, so that the sampling needle point can be accurately aligned with the mass spectrum sampling nozzle position.
Description
Technical Field
The invention relates to the technical field of single cell measurement, in particular to a multidimensional adjusting device for efficient ionization of single cells.
Background
Single cell analysis has attracted much attention because it can provide important information for disease detection, gene sequencing, and metabonomics. The full-automatic single-cell mass spectrum sample injector with the publication number of CN110197786A extracts single intracellular substances such as cytoplasm, cell nucleus and the like, and then automatically sends the substances to a sample inlet of a mass spectrometer for component analysis, and a sample injection 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 needle tip sample introduction, the sampling needle tip cannot be aligned to the sample introduction end of the mass spectrum. The CN107863286A Mass Spectrometry interface device for in-situ lysis and on-line ionization detection of living unicells integrates cell in-situ lysis, continuous flow control of lysate, and cell lysis component liquid driving, on-line real-time ionization and detection into a whole by adjusting target cells to be under a microfluidic probe through an electric control objective table, can perform in-situ fixed-point treatment on adherent cells or cells on tissue slices cultured in a culture dish, realizes in-situ mass spectrometry detection, and realizes in-situ full component analysis of unicells. CN110333282A discloses a single-cell analyzer with a flow sample introduction mode and a flow focusing mode, a sample introduction system and a flow focusing device, which has the advantages of large sample flux and high analysis speed, can reduce the cell loss in sample introduction and can improve the transmission efficiency of cell particles.
The existing single cell online analysis method mainly emphasizes the operation of continuous single cells. Emphasizes the continuous sample introduction process in the single cell analysis process, and lacks the operation of sampling single cells and in-situ needle points. In the prior art, the position of a skin-lift sampling needle is not adjusted, the position is usually only 2-3 dimensions, the manual or precision is too low, and the position of a single cell cannot be adjusted in the continuous sample introduction process. The ionization source for single cell operation has a distance and size difference with the position of the sample inlet, which results in low ionization efficiency.
Disclosure of Invention
In accordance with the above-mentioned technical problem, a multi-dimensional modulation device for efficient ionization of single cells is provided. The technical means adopted by the invention are as follows:
the utility model provides a multidimension adjusting device for high-efficient ionization of unicellular, includes sampling mechanism and the multidimension adjustment displacement platform that is used for adjusting sampling mechanism space position appearance, sampling mechanism is including the ionization skin liter that is used for drawing intracellular tissue liquid and the electrode slice that is used for providing ionization voltage, ionization skin liter advances the appearance spray needle with there is preset distance between the electrode slice, multidimension adjustment displacement platform includes multidimension big step adjustment mechanism and the meticulous adjustment mechanism of multidimension, multidimension big step adjustment mechanism is used for adjusting the distance between ionization skin liter advances the appearance spray needle and the quality detection mechanism, the meticulous adjustment mechanism of multidimension is used for adjusting the relative position relation between spray needle and the electrode slice.
Furthermore, the multi-dimensional 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 multi-dimensional fine adjusting mechanism, and the bottoms of the supporting legs are connected through a connecting rod.
Furthermore, the top end of the head connecting piece is provided with a guide rail type structure, and the multi-dimensional fine adjusting mechanism can slide on the guide rail type structure, so that the position of the large stride can be adjusted.
Furthermore, 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 adjust the needle tip clamping mechanism in an X-axis mode, a Y-axis mode and a Z-axis mode, and further adjust the space position of the ionized skin-lift sampling spray needle installed on the three-dimensional adjustment base, the needle tip clamping mechanism can adjust the pitching angle and the deflection angle of the ionized skin-lift sampling spray needle, so that the relative position relation between the ionized skin-lift sampling spray needle and an electrode plate is changed, and the electrode plate can transmit high pressure and ionize single cell samples in the ionized skin-lift sampling spray needle.
Further, the electrode plate is electrified to be in a direct current high voltage range or a sine wave high voltage range, the direct current high voltage range is 2-5kV, and the sine wave high voltage frequency is 0.1-1 kHz.
The invention has the following advantages:
1. the design precision adjustment adjusts two kinds of regulation modes that combine together with big step, lets skin liter advance the needle and the adjustment mode of quality detector under different environment, under the condition far away, adopts big step to adjust, can be on a large scale, adjusts the certain distance, has more extensive control range. The design is added with a high-precision fine adjustment structure, so that sample introduction can be performed on the mass spectrum, the micron regulation range is adopted, and the sample introduction needle tip can be accurately aligned with the mass spectrum sample introduction nozzle position.
2. But the fine adjustment structure of design X axle is adjusted, and Y axle is adjusted, and Z axle is adjusted, and the angle modulation of every single move and deflection, the all-round regulation of five dimensions of doing avoids the sampling needle point because the uncontrollable nature that the adjusting position caused, will adjust the precision and realize micron order precision, and arbitrary change distance adjusts ionization intensity.
3. The position of the high-voltage electrode plate is close to but not in contact with the sampling spray needle, and the mode is adopted to avoid the pollution to the unicellular sample caused by the fact that the discharge wire is in contact with the inside of the sampling needle tip. The needle is placed at the position close to the bottom end of the sample injection needle, so that the needle tip can be discarded. Meanwhile, the position of the electrode plate is close to the needle tip, so that high voltage can be transmitted, and a single-cell sample in the sample injection spray needle is ionized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Fig. 1 is a schematic view 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 diagram of the present invention in connection with a mass spectrometer.
In the figure: 1. a sample injection needle; 2. an X-axis fine adjustment mechanism; 3. a Y-axis fine adjustment mechanism; 4. a Z-axis fine adjustment mechanism; 5. a needle tip angle adjusting mechanism; 6. an electrode sheet; 7. a high pressure support bar; 8. a large stride angle adjusting mechanism; 9. a large stride position adjusting mechanism; 10. connecting a support frame; 11. the high-voltage electrode is connected with the support frame; 12. a mass spectrometry detector; 21. a multi-dimensional large-stride adjustment mechanism; 22. a multi-dimensional fine adjustment mechanism; 23. a sample feeding mechanism.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
As shown in fig. 1 to 5, the embodiment discloses a multidimensional adjustment device for efficient ionization of single cells, which includes a sampling mechanism 23 and a multidimensional adjustment displacement platform for adjusting the spatial pose of the sampling mechanism, wherein the sampling mechanism includes an ionization skin-lift sampling nozzle needle 1 for extracting intracellular tissue fluid and an electrode plate 6 for providing ionization voltage, a preset distance exists between the ionization skin-lift sampling nozzle needle and the electrode plate, the multidimensional adjustment displacement platform includes a multidimensional large step adjustment mechanism 21 and a multidimensional fine adjustment mechanism 22, the multidimensional large step adjustment mechanism is used for adjusting the distance between the ionization skin-lift sampling nozzle needle and a quality detection mechanism, the multidimensional fine adjustment mechanism is used for adjusting the relative position relationship between the nozzle needle and the electrode plate, and in the embodiment, the quality detection mechanism is a mass spectrometer 12.
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 a connecting rod. Mostly, it can accomplish big step position control function and big step angle modulation function to stride a step adjustment mechanism greatly, and big step position control mechanism 9 mainly includes the top of head connecting piece is equipped with guide rail type structure, the meticulous adjustment mechanism of multidimension can slide above that, and then carries out the position control of striding a step greatly. The large-stride angle adjusting mechanism 8 is mainly connected to the middle supporting leg in a hinged mode through a supporting leg structure, and can be a tripod type support.
The lower end of the sample injection needle is attached to the electrode plate, the electrode plate is a metal sheet and is connected with a high-voltage power supply, and the electrode plate is connected to the base of the multidimensional fine adjustment mechanism through a high-voltage support rod 7 and a high-voltage electrode connection support frame 11. And applying high voltage on the metal sheet to enable the position of the sample injection needle to form an ion flow. The electrode plate is electrified to be in a direct current high voltage range or a sine wave high voltage range, the direct current high voltage range is 2-5kV, and the sine wave high voltage frequency is 0.1-1 kHz.
The multidimensional fine adjustment mechanism comprises a three-dimensional adjustment base and a needle point clamping mechanism located on the multidimensional fine adjustment mechanism through a connecting support frame 10, the three-dimensional adjustment base is installed on the multidimensional large-step adjustment mechanism, the three-dimensional adjustment base can adjust the needle point clamping mechanism in an X-axis, a Y-axis and a Z-axis through an X-axis fine adjustment mechanism 2, a Y-axis fine adjustment mechanism 3 and a Z-axis fine adjustment mechanism 4, so as to adjust the space position of an ionized pico-liter sample injection spray needle installed on the three-dimensional adjustment base, the needle point clamping mechanism can adjust the pitching angle and the deflection angle of the ionized pico-liter sample injection spray needle through a needle point angle adjustment mechanism 5, so that the relative position relation between the ionized pico-liter sample injection spray needle and an electrode plate is changed, the electrode plate can transmit high voltage to ionize a single cell sample in the ionized pico-liter sample injection spray needle, the electrode plate position keeps fixed with the needle point distance, and high-voltage electrode plate can realize fine adjustment with the needle point position, lets the electrode plate as much as possible with sample needle point contact, effectively increases ionization efficiency and reduces ionization efficiency. The invention can effectively and finely adjust the position of the skin-lift sample injection needle, control the ionization efficiency and improve the high-efficiency ionization of single cells.
In this embodiment, needle point fixture includes main frame body and the mechanism of screwing/loosening of setting on main frame body, the root of needle point is fixed on the cylinder fixed part, the mechanism of screwing/loosening is used for fixing the cylinder fixed part, and the mechanism of screwing/loosening can choose to make the fixed or stable jack catch of centre gripping of low-priced screw rod fixed or mechanism that suits to dismantle or fix the needle point at any time such as electric control. When the jack catch is selected for use, the embodiment is also matched with a corresponding clamp, and after the needle tip is clamped by the clamp, the jack catch clamps the clamp to complete the fixation of the needle tip. 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 can be adjusted through the rolling device.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (5)
1. The utility model provides a multidimension adjusting device for high-efficient ionization of unicellular, its characterized in that, including advancing the mechanism and being used for adjusting the multidimension adjustment displacement platform of advancing the mechanism space position appearance of appearance, advance the mechanism including the ionization skin liter that is used for drawing intracellular tissue liquid advance the injection needle and be used for providing ionization voltage's electrode slice, ionization skin liter advance the injection needle with there is preset distance between the electrode slice, multidimension adjustment displacement platform includes the great step adjustment mechanism of multidimension and the meticulous adjustment mechanism of multidimension, the great step adjustment mechanism of multidimension is used for adjusting the distance between ionization skin liter advances the injection needle and the quality detection mechanism, the meticulous adjustment mechanism of multidimension is used for adjusting the relative position relation between injection needle and the electrode slice.
2. The multi-dimensional adjusting device for efficient ionization of single cells as claimed in claim 1, wherein the multi-dimensional large-step 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 multi-dimensional fine adjusting mechanism, and the bottoms of the supporting legs are connected through a connecting rod.
3. The multi-dimensional adjusting device for efficient ionization of single cells as claimed in claim 2, wherein the top end of the head connecting piece is provided with a guide rail type structure on which the multi-dimensional fine adjusting mechanism can slide for position adjustment with a large step.
4. The multidimensional regulating device for high-efficiency ionization of single cells according to any one of claims 1 to 3, wherein the electrode plates are electrified with direct current high voltage or high voltage with sine waves, the range of the direct current high voltage is 2-5kV, and the high voltage frequency with the sine waves is 0.1-1 kHz.
5. The multi-dimensional conditioning device for efficient ionization of single cells according to claim 4, the multi-dimensional fine adjustment mechanism comprises a three-dimensional adjustment base and a needle point clamping mechanism located on the three-dimensional adjustment base, the three-dimensional adjusting base is arranged on the multi-dimensional large-step adjusting mechanism and can adjust the needle point clamping mechanism in an X axis, a Y axis and a Z axis, further adjusting the spatial position of the ionized skin-lift sample injection spray needle arranged on the needle tip clamping mechanism, adjusting the pitching angle and the deflection angle of the ionized skin-lift sample injection spray needle by the needle tip clamping mechanism, so that the relative position relationship between the ionized picoliter sample injection spray needle and the electrode plate is changed, the electrode plate can transmit high voltage to ionize the single cell sample in the ionized picoliter sample injection spray needle.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011092157.3A CN114361007A (en) | 2020-10-13 | 2020-10-13 | Multidimensional adjusting device for efficient ionization of single cells |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011092157.3A CN114361007A (en) | 2020-10-13 | 2020-10-13 | Multidimensional adjusting device for efficient ionization of single cells |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6495823B1 (en) * | 1999-07-21 | 2002-12-17 | The Charles Stark Draper Laboratory, Inc. | Micromachined field asymmetric ion mobility filter and detection system |
| US20060255289A1 (en) * | 2005-05-13 | 2006-11-16 | Cygan Thomas R | Sample handling mechanisms and methods for mass spectometry |
| US20110215233A1 (en) * | 2007-07-20 | 2011-09-08 | Akos Vertes | 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 |
| CN103069539A (en) * | 2010-08-19 | 2013-04-24 | 莱克公司 | Time-of-flight mass spectrometer with accumulating electron impact ion source |
| CN103972019A (en) * | 2014-05-12 | 2014-08-06 | 清华大学 | Non-contact direct-current induction electrospray ionization device and method |
| JP2016011942A (en) * | 2014-06-02 | 2016-01-21 | 努 升島 | High functionalization of nano spray ionization and chip |
| CN209587579U (en) * | 2019-01-24 | 2019-11-05 | 李建刚 | A kind of adjustment structure for height of leveling instrument |
-
2020
- 2020-10-13 CN CN202011092157.3A patent/CN114361007A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6495823B1 (en) * | 1999-07-21 | 2002-12-17 | The Charles Stark Draper Laboratory, Inc. | Micromachined field asymmetric ion mobility filter and detection system |
| US20060255289A1 (en) * | 2005-05-13 | 2006-11-16 | Cygan Thomas R | Sample handling mechanisms and methods for mass spectometry |
| US20110215233A1 (en) * | 2007-07-20 | 2011-09-08 | Akos Vertes | 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 |
| CN103069539A (en) * | 2010-08-19 | 2013-04-24 | 莱克公司 | Time-of-flight mass spectrometer with accumulating electron impact ion source |
| CN103972019A (en) * | 2014-05-12 | 2014-08-06 | 清华大学 | Non-contact direct-current induction electrospray ionization device and method |
| JP2016011942A (en) * | 2014-06-02 | 2016-01-21 | 努 升島 | High functionalization of nano spray ionization and chip |
| 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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