CN116351487B - A hydroxyl radical irradiation labeling device based on X-rays - Google Patents
A hydroxyl radical irradiation labeling device based on X-raysInfo
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- CN116351487B CN116351487B CN202310229474.2A CN202310229474A CN116351487B CN 116351487 B CN116351487 B CN 116351487B CN 202310229474 A CN202310229474 A CN 202310229474A CN 116351487 B CN116351487 B CN 116351487B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
- B01F35/7176—Feed mechanisms characterised by the means for feeding the components to the mixer using pumps
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0819—Microarrays; Biochips
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0454—Moving fluids with specific forces or mechanical means specific forces radiation pressure, optical tweezers
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- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Analysing Materials By The Use Of Radiation (AREA)
Abstract
本发明提供一种基于X‑射线的羟基自由基辐照标记装置，包括：微流控混合器、双通道注射泵、移动平台和控制单元，微流控混合器包括微流道结构和辐照窗口，微流道结构包括第一进样流道、第二进样流道、混合流道、输出流道和辐照流道；辐照窗口与辐照流道对应设置；双通道注射泵包括第一通道注射泵和第二通道注射泵，分别与第一进样流道、第二进样流道连接；移动平台与微流控混合器连接；控制单元分别与双通道注射泵、移动平台电性连接。本发明中的装置适用于基于同步辐射装置的光束线站，能够实现X‑射线的光束中心与辐照窗口的快速校准和毫秒时间尺度样品快速混合，最终实现快速时间尺度的羟基自由基标记。
The present invention provides an X-ray-based hydroxyl radical irradiation labeling device, comprising: a microfluidic mixer, a dual-channel syringe pump, a mobile platform, and a control unit, wherein the microfluidic mixer comprises a microfluidic structure and an irradiation window, wherein the microfluidic structure comprises a first sample inlet channel, a second sample inlet channel, a mixing channel, an output channel, and an irradiation channel; the irradiation window is arranged corresponding to the irradiation channel; the dual-channel syringe pump comprises a first channel syringe pump and a second channel syringe pump, which are respectively connected to the first sample inlet channel and the second sample inlet channel; the mobile platform is connected to the microfluidic mixer; and the control unit is electrically connected to the dual-channel syringe pump and the mobile platform, respectively. The device of the present invention is suitable for a beamline station based on a synchrotron radiation device, and can realize rapid calibration of the X-ray beam center and the irradiation window and rapid mixing of samples on a millisecond time scale, ultimately realizing rapid time-scale hydroxyl radical labeling.
Description
Technical Field
The invention belongs to the technical field of experimental equipment, and particularly relates to a hydroxyl radical irradiation marking device based on X-rays.
Background
The free radical imprinting mass spectrometry can study protein structure and structure interaction dynamics on a rapid time scale (millisecond and sub millisecond level), has high sensitivity and small sample demand, is compatible with complex sample systems (protein mixture and even living cell sample processing analysis), and has the key technical problems that hydroxyl free radicals are generated based on solvent induction, the oxidation modification is carried out on the amino acid side chains of solutes (mainly aiming at proteins), and different amino acid sites in the solutes are marked in real time along with the time scale change. The synchronous radiation device is the key point for realizing the rapid time scale hydroxyl radical marking, an X-ray Western blotting method is firstly carried out in 2004 by the eastern coast Bruce Haievin national laboratory depending on an advanced synchronous radiation light source (NSLS-X28C), and a first beam line and an experimental station (Sayan Gupta-Journal of Synchrotron Radiation 2014) which are specially used for the Western blotting mass spectrometry are built. During the NSLS switch-off upgrade to NSLSII, in order not to affect development and application of western blot mass spectrometry techniques, the american scientist conducted screening tests again on line stations of multiple light sources in the united states, and the lorensberk national laboratory ALS located on the west coast was selected for migration of relevant laboratory stations (5.3.1-the earliest used wire harness; 3.2.1-in-use; 3.3.1-under construction, awuri Asuru-Journal of Synchrotron Radiation 2018). Subsequently, in view of the development of western blot mass spectrometry technology and the application of the leading edge, researchers have rebuilt and upgraded western blot laboratory stations (XFP) again at newly upgraded bruexploiting national laboratory NSLS II light source. These approaches have greatly driven the development of protein radical blot mass spectrometry techniques in the united states and support the yield of a number of major technological achievements (e.g., yiiP-Nature 2014;orange carotenoid protein-Science 2015; gpcr-Cell 2019).
The free radical imprinting mass spectrometry is proved to be a novel technical method which is powerful and universal and can analyze microsecond to second time scales, but the method belongs to the field of complete blank research in China and has wide and important application prospect. The Shanghai synchrotron radiation device belongs to a third generation medium-energy synchrotron radiation device, a plurality of line stations can provide high-flux X-rays with 10 14 photons per second, a sufficient number of hydroxyl free radicals can be generated in a biological macromolecule solution sample through millisecond-level irradiation, the performance completely meets the basic requirements of developing a free radical imprinting mass spectrometry, but an X-ray hydroxyl free radical in-situ irradiation marking device based on the synchrotron radiation device needs to be developed, and the X-ray induced free radical imprinting marking is utilized to realize the establishment of an in-situ sampling system, the design of an X-ray irradiation device and the configuration of an on-line sample collecting device after irradiation, so that corresponding technical flows and methods are established.
Disclosure of Invention
In view of the above-described drawbacks of the prior art, an object of the present invention is to provide an X-ray based hydroxyl radical irradiation marking device that induces biological macromolecules by X-ray irradiation of a synchrotron radiation device for rapid time-scale hydroxyl radical marking.
To achieve the above and other related objects, the present invention provides an X-ray based hydroxyl radical irradiation marking device comprising:
the microfluidic mixer comprises a microfluidic channel structure and an irradiation window, wherein the microfluidic channel structure comprises a first sample injection channel, a second sample injection channel, a mixing channel, an output channel and an irradiation channel, the first sample injection channel and the second sample injection channel are respectively positioned at two sides of the mixing channel and are mutually communicated, the output channel is positioned below the mixing channel, the irradiation channel is positioned below the mixing channel, the output channel and the irradiation channel are mutually communicated, and a mixed sample in the mixing channel enters the irradiation channel through the output channel;
The double-channel injection pump comprises a first channel injection pump and a second channel injection pump, and the injection end of the first channel injection pump is connected with the first sample injection flow channel; the injection end of the second channel injection pump is connected with the second sample injection flow channel, and the first channel injection pump and the second channel injection pump respectively inject samples into the micro-flow channel structure;
The mobile platform is connected with the microfluidic mixer and is used for adjusting the position of the microfluidic mixer to realize that the beam center of X-rays is aligned with the irradiation window;
and the control unit is respectively and electrically connected with the double-channel injection pump and the mobile platform.
Preferably, the microfluidic mixer is formed by laminating a mixing layer, a window sealing layer, a sealing layer and a cover plate;
the micro-channel structure is arranged on the mixing layer in a penetrating way;
The two window sealing layers are respectively arranged on two side surfaces of the mixing layer, and the window sealing layers have X-ray penetrability and are used for sealing the micro-channel structure;
The sealing layers comprise a first sealing layer and a second sealing layer, and the first sealing layer and the second sealing layer are respectively positioned on one surface of the two window sealing layers, which is far away from the mixed layer;
The cover plate layer comprises a first cover plate and a second cover plate, the first cover plate is positioned on one surface of the first sealing layer, which is far away from the mixed layer, and the second cover plate is positioned on one surface of the second sealing layer, which is far away from the mixed layer;
The irradiation window is communicated with the sealing layer and the cover plate layer, the first cover plate, the first sealing layer and the window sealing layer adjacent to the first sealing layer are communicated with each other, a first sample inlet, a second sample inlet and a sample outlet are formed in the first cover plate, the first sample inlet is communicated with the first sample inlet flow channel, the second sample inlet is communicated with the second sample inlet flow channel, the sample outlet is located below the irradiation window and is communicated with the irradiation flow channel, and a sample marked by hydroxyl radical irradiation is led out from the sample outlet.
Preferably, the material of the window sealing layer is polyimide film.
Preferably, the microfluidic mixer is made of stainless steel, and the micro-channel structure is formed by laser etching.
Preferably, the width of the first sample injection flow channel is consistent with the width of the second sample injection flow channel, the width of the output flow channel is not smaller than the width of the first sample injection flow channel, and the width of the output flow channel is smaller than the width of the irradiation flow channel.
Preferably, the width of the irradiation flow channel is 0.25 mm-0.3 mm.
Preferably, the moving platform is a two-dimensional moving platform, and the two-dimensional moving platform comprises a horizontal position adjusting module and a vertical position adjusting module, wherein the horizontal position adjusting module is used for adjusting the movement of the microfluidic mixer in the horizontal direction, and the vertical position adjusting module is used for adjusting the movement of the microfluidic mixer in the vertical direction so as to align the irradiation window with the beam center of the X-ray.
Preferably, the horizontal position adjusting module comprises a horizontal base, a horizontal lead screw, a horizontal sliding block and a horizontal stepping motor;
The horizontal lead screw is fixedly arranged on the horizontal base along the horizontal direction, the horizontal sliding block is arranged on the horizontal lead screw, the microfluidic mixer is fixedly connected with the horizontal sliding block, the horizontal stepping motor is connected with the horizontal lead screw, and the horizontal stepping motor drives the horizontal sliding block to move in the horizontal direction through the horizontal lead screw, so that the microfluidic mixer is driven to move in the horizontal direction.
Preferably, the vertical position adjusting module comprises a vertical base, a vertical screw rod, a vertical sliding block and a vertical stepping motor;
The vertical lead screw is arranged on the vertical base along the vertical direction, the vertical sliding block is arranged on the vertical lead screw, the vertical sliding block is fixedly connected with the horizontal base, the vertical stepping motor is connected with the vertical lead screw, the vertical stepping motor drives the vertical sliding block to move in the vertical direction through the vertical lead screw, and then the vertical sliding block drives the horizontal sliding block to move in the vertical direction through the horizontal base.
Preferably, a supporting rod is fixed below the horizontal sliding block, and the microfluidic mixer is fixedly connected to the lower side of the horizontal sliding block through the supporting rod.
As described above, the X-ray-based hydroxyl radical irradiation marking device of the invention has the following beneficial effects:
The hydroxyl radical irradiation marking device adopts the control unit to control the double-channel injection pump and the mobile platform with high precision, realizes the rapid calibration of the beam center and the irradiation window of X-rays, adopts the microfluidic mixer to realize the rapid mixing of millisecond time scale samples, finally utilizes the X-ray irradiation to induce biological macromolecules to realize the hydroxyl radical marking of the rapid time scale, has low requirement on environment, and is suitable for the X-ray hydroxyl radical irradiation marking based on the synchronous radiation device.
According to the hydroxyl radical irradiation marking device based on X-rays, through adjusting the sample injection flow rates of the first channel injection pump and the second channel injection pump, the time resolution of 1 millisecond sample mixing can be realized at maximum, the irradiation marking efficiency can reach 0.5 millisecond, and the device is suitable for experiments at different experiment terminals.
Drawings
Fig. 1 is a schematic structural view showing a hydroxyl radical irradiation marking device based on X-rays in an embodiment of the present invention.
Fig. 2 is a schematic structural diagram of a two-dimensional mobile platform according to an embodiment of the invention.
Fig. 3 is a schematic diagram showing an exploded structure of a microfluidic mixer in an embodiment of the present invention.
Fig. 4 is a schematic structural diagram of a micro flow channel structure according to an embodiment of the invention.
Reference numerals
10. Microfluidic mixer
100. Hybrid layer
101. Micro-channel structure
1011. First sample injection flow channel
1012. Second sample injection flow channel
1013. Mixing runner
1014. Output runner
1015. Irradiation flow channel
1021,1022 Window sealing layer
1031. First sealing layer
1032. Second sealing layer
1041. A first cover plate layer
1042. A second cover plate layer
105. Irradiation window
106. First sample inlet
107. Second sample inlet
108. Sample outlet
201. First channel syringe pump
202. Second channel syringe pump
300. Two-dimensional mobile platform
3011. Horizontal base
3012. Horizontal screw
3013. Horizontal sliding block
3014. Horizontal stepping motor
3021. Vertical base
3022. Vertical screw
3023. Vertical sliding block
3024. Vertical stepping motor
303. Support bar
400. Control unit
Detailed Description
Further advantages and effects of the present invention will become apparent to those skilled in the art from the disclosure of the present invention, which is described by the following specific examples.
Please refer to fig. 1 to 4. It should be understood that the structures, proportions, sizes, etc. shown in the drawings are for illustration purposes only and should not be construed as limiting the invention to the extent that it can be practiced, since modifications, changes in the proportions, or otherwise, used in the practice of the invention, are not intended to be critical to the essential characteristics of the invention, but are intended to fall within the spirit and scope of the invention. Also, the terms such as "upper," "lower," "left," "right," "middle," and "a" and the like recited in the present specification are merely for descriptive purposes and are not intended to limit the scope of the invention, but are intended to provide relative positional changes or modifications without materially altering the technical context in which the invention may be practiced.
Referring to fig. 1, the invention provides an X-ray-based hydroxyl radical irradiation marking device, which comprises a microfluidic mixer 10, a dual-channel injection pump, a moving platform and a control unit 400, wherein the microfluidic mixer 10 comprises a microfluidic channel structure 101 and an irradiation window 105, the microfluidic channel structure 101 comprises a first injection channel 1011, a second injection channel 1012, a mixing channel 1013, an output channel 1014 and an irradiation channel 1015, the first injection channel 1011 and the second injection channel 1012 are respectively positioned at two sides of the mixing channel 1013 and are mutually communicated, the output channel 1014 is positioned below the mixing channel 1013, the irradiation channel 1015 is positioned below the mixing channel 1013, the output channel 1014 and the irradiation channel 1015 are mutually communicated, a mixed sample in the mixing channel 1013 enters the irradiation channel 1015 through the output channel 1014, the irradiation window 105 is correspondingly arranged with the irradiation channel 1015, an X-ray beam is irradiated to the irradiation channel 1015 from the irradiation window 105 for marking the mixed sample, the first channel injection pump 201 and the second channel injection pump 202 are respectively positioned at two sides of the mixing channel injection channel, the injection end of the first channel pump 201 and the second channel injection pump 202 are respectively connected with the first channel injection pump 202, the second channel injection pump and the micro-channel injection channel 10 are respectively aligned with the moving platform and the micro-channel injection channel 10, and the micro-channel injection device is respectively connected with the moving platform and the micro-channel injection pump 10.
Specifically, the control unit 400 precisely controls the sample injection rates of the first channel injection pump 201 and the second channel injection pump 202 respectively, so as to realize mixing of samples in different proportions, the mixing time is controlled by adjusting the sample injection rates, the samples flow to the irradiation flow passage 1015 through the output flow passage 1014 after being mixed in the mixing flow passage 1013, the control unit 400 drives the microfluidic mixer 10 to move by precisely controlling the moving platform, the rapid calibration of the beam center of the X-ray is realized, and the X-ray beam irradiates the irradiation window 105, so that the hydroxyl radical marking of the mixed samples is realized.
As an example, referring to fig. 3, the microfluidic mixer 10 is laminated by a mixing layer 100, a window sealing layer (including a window sealing layer 1021 adjacent to a first sealing layer 1031 and a window sealing layer 1022 adjacent to a second sealing layer 1032), a sealing layer, and a cover plate; the micro-channel structure 101 is arranged on the mixed layer 100 in a penetrating mode, two sealing layers (comprising a sealing layer 1021 adjacent to the first sealing layer 1031 and a sealing layer 1022 adjacent to the second sealing layer 1032) are arranged on two sides of the mixed layer 100, the two sealing layers (comprising the sealing layer 1021 adjacent to the first sealing layer 1031 and the sealing layer 1022 adjacent to the second sealing layer 1032) are respectively arranged on two sides of the mixed layer 100, the sealing layers (comprising the sealing layer 1021 adjacent to the first sealing layer 1031 and the sealing layer 1022 adjacent to the second sealing layer 1032) are provided with X-ray penetrability and are used for sealing the micro-channel structure 101, the sealing layers comprise a first sealing layer 1031 and a second sealing layer 1032, the first sealing layer 1031 and the second sealing layer 1032 are respectively arranged on one side of the two sealing layers (comprising the sealing layer 1021 adjacent to the first sealing layer 1031 and the sealing layer 1022 adjacent to the second sealing layer 1032) which is far away from the mixed layer 100, the first cover plate layer 1031 and the second cover plate are arranged on one side of the first cover plate 1031 far away from the mixed layer 100, the second cover plate is arranged on the second cover plate layer 1031 and is communicated with the first sealing layer 1031 and the sample inlet port 107, the sample inlet port is communicated with the first sealing layer 1031 and the sample inlet port 107 is arranged on the sealing layer 107, the sample outlet 108 is positioned below the irradiation window 105 and is communicated with the irradiation flow passage 1015, and the mixed sample marked by hydroxyl radical irradiation is led out from the sample outlet 108.
Specifically, referring to fig. 3, the microfluidic mixer 10 sequentially includes a first cover plate layer 1041, a first sealing layer 1031, a window sealing layer 1021, a mixing layer 100, a window sealing layer 1022, a second sealing layer 1032, and a second cover plate layer 1042, where the first cover plate layer 1041 and the second cover plate layer 1042 can be fixed by bolts, and the layers are sequentially fixed together to form the microfluidic mixer 10.
In addition, the injection end of the first channel injection pump 201 is connected to the first sample inlet 106 through a fluid line, and injects a sample into the first sample injection channel 1011, and the injection end of the second channel injection pump 202 is connected to the second sample inlet 107 through a fluid line, and injects a sample into the second sample injection channel 1012, and each time the sample is injected, the injection flow rate and the flow velocity of the sample can be set independently, so as to control the mixing reaction time.
In this embodiment, the mixed sample marked by hydroxyl radical irradiation is led out from the sample outlet 108 and then enters the quencher to perform a mass spectrometry experiment, however, in other embodiments, the mixed sample can be used for other experiment terminals to perform experiments, and the experiment is not limited excessively.
As an example, the material of the window sealing layer (including the window sealing layer 1021 adjacent to the first sealing layer 1031 and the window sealing layer 1022 adjacent to the second sealing layer 1032) is a polyimide film.
Specifically, the polyimide film has extremely high X-ray penetrability, and X-rays can directly penetrate the polyimide film and irradiate the mixed layer 100.
As an example, the microfluidic mixer 10 is made of stainless steel, and the micro flow channel structure 101 is processed by laser etching.
Specifically, the microfluidic mixer 10 is formed by laminating a mixing layer 100, a window sealing layer (including a window sealing layer 1021 adjacent to a first sealing layer 1031 and a window sealing layer 1022 adjacent to a second sealing layer 1032), sealing layers and a cover plate, wherein the materials of the layers are all stainless steel materials, and the micro-channel structure 101 is sealed by using flexibility of metal, and the micro-channel structure 101 is formed by adopting laser etching, and a specific laser etching process is a process well known to those skilled in the art, and will not be described herein in detail.
As an example, the width of the first injection flow channel 1011 is identical to the width of the second injection flow channel 1012, the width of the output flow channel 1014 is not less than the width of the first injection flow channel 1011, and the width of the output flow channel 1014 is less than the width of the irradiation flow channel 1015.
Specifically, referring to fig. 4, a sample injected through a first injection flow channel 1011 and a sample injected through a second injection flow channel 1012 are mixed in a mixing flow channel 1013, and the two samples respectively enter the mixing flow channel 1013 at a higher flow rate, and then enter an irradiation flow channel 1015 through an output flow channel 1014, wherein the width of the output flow channel 1014 is not less than the width of the first injection flow channel 1011, and the width of the output flow channel 1014 is less than the width of the irradiation flow channel 1015, so that the mixed sample forms turbulence in the mixing flow channel 1013, and the purpose of rapid mixing is achieved. By way of example, the irradiation flow path 1015 has a width of 0.25mm to 0.3mm.
Specifically, the width of the irradiation flow path 1015 includes values in any range of 0.25mm, 0.26mm, 0.27mm, 0.28mm, 0.29mm, 0.3mm, etc., and may be specifically adjusted according to the actual use. As an example, the moving platform is a two-dimensional moving platform 300, and the two-dimensional moving platform 300 includes a horizontal position adjustment module for adjusting the movement of the microfluidic mixer 10 in the horizontal direction and a vertical position adjustment module for adjusting the movement of the microfluidic mixer 10 in the vertical direction, thereby aligning the irradiation window 105 with the beam center of the X-rays.
As an example, referring to fig. 2, the horizontal position adjusting module includes a horizontal base 3011, a horizontal screw 3012, a horizontal slider 3013, and a horizontal stepping motor 3014, wherein the horizontal screw 3012 is fixedly mounted on the horizontal base 3011 along a horizontal direction, the horizontal slider 3013 is mounted on the horizontal screw 3012, the microfluidic mixer 10 is fixedly connected to the horizontal slider 3013, the horizontal stepping motor 3014 is connected to the horizontal screw 3012, and the horizontal stepping motor 3014 drives the horizontal slider 3013 to move in the horizontal direction through the horizontal screw 3012, so as to drive the microfluidic mixer 10 to move in the horizontal direction.
Specifically, the control unit 400 controls the horizontal stepping motor 3014 to precisely move according to the received adjustment signal, the horizontal stepping motor 3014 drives the horizontal slide block 3013 to move in the horizontal direction through the horizontal lead screw 3012, and the horizontal slide block 3013 drives the microfluidic mixer 10 to move in the horizontal direction.
As an example, referring to fig. 2, the vertical position adjustment module includes a vertical base 3021, a vertical screw 3022, a vertical slider 3023, and a vertical stepping motor 3024, wherein the vertical screw 3022 is mounted on the vertical base 3021 in a vertical direction, the vertical slider 3023 is mounted on the vertical screw 3022, the vertical slider 3023 is fixedly connected to the horizontal base 3011, the vertical stepping motor 3024 is connected to the vertical screw 3022, the vertical stepping motor 3024 drives the vertical slider 3023 to move in a vertical direction through the vertical screw 3022, and the vertical slider 3023 drives the horizontal slider 3013 to move in a vertical direction through the horizontal base 3011.
Specifically, the control unit 400 controls the vertical stepping motor 3024 to precisely move according to the received adjustment signal, the vertical stepping motor 3024 drives the vertical slider 3023 to move in the vertical direction through the vertical screw rod, the vertical slider 3023 is fixed to the horizontal base 3011, the vertical slider 3023 drives the horizontal base 3011 to move in the vertical direction, and then the horizontal base 3011 drives the horizontal slider 3013 to move in the vertical direction, and the horizontal slider 3013 drives the microfluidic mixer 10 to move in the vertical direction.
As an example, a support rod 303 is fixed below the horizontal slider 3013, and the microfluidic mixer 10 is fixedly connected to the lower side of the horizontal slider 3013 by the support rod 303.
Specifically, referring to fig. 2, the movement of the horizontal slider 3013 in the horizontal direction and the vertical direction drives the support rod 303 to move synchronously, so as to drive the microfluidic mixer 10 to move synchronously, where the support rod 303 is only used as an adaptor, and the specific structure of the support rod 303 is not excessively limited herein.
For a better understanding of the X-ray-based hydroxyl radical irradiation marking device of the present invention, the hydroxyl radical irradiation marking device of the present invention will be described below with reference to actual specific experiments.
In this embodiment, the thickness of the mixed layer 100 of the microfluidic mixer 10 in the X-ray-based hydroxyl radical irradiation marking device is 0.4mm, the widths of the first injection flow channel 1011 and the second injection flow channel 1012 are 0.08mm, the width of the output flow channel 1014 is 0.12mm, the width of the irradiation flow channel 1015 is 0.25mm, and 1 millisecond of rapid mixing can be achieved when the injection rates of the first channel injection pump 201 and the second channel injection pump 202 are 8 ml/min.
The device is arranged at an experimental line station, the moving platform is used for driving the microfluidic mixer 10 to move in the horizontal direction and the vertical direction, so that the beam center of X-rays is aligned with the irradiation window 105 of the microfluidic mixer 10, the experimental conditions are that the energy of the X-rays is 12KeV, the spot size of the X-rays is 0.3mm multiplied by 0.05mm, and the irradiation marking time of hydroxyl radicals of the X-rays is 0.5 millisecond when the sample injection rate of the first channel injection pump 201 and the second channel injection pump 202 is 8 ml/min.
In summary, the hydroxyl radical irradiation marking device adopts the control unit to control the dual-channel injection pump and the mobile platform with high precision, realizes the rapid calibration of the beam center and the irradiation window of X-rays, adopts the microfluidic mixer to realize the rapid mixing of millisecond time scale samples, finally utilizes the X-ray irradiation to induce biological macromolecules to realize the hydroxyl radical marking of the rapid time scale, has low environmental requirements, is suitable for the X-ray hydroxyl radical irradiation marking based on a synchronous radiation device, and can realize the rapid mixing time resolution of 1 millisecond samples and the irradiation marking efficiency of 0.5 millisecond by adjusting the sample injection flow rates of the first channel injection pump and the second channel injection pump, and the device is suitable for experiments of different experiment terminals. Therefore, the invention effectively overcomes various defects in the prior art and has high industrial utilization value.
The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (7)
1. An X-ray based hydroxyl radical irradiation marking device, the device comprising:
The microfluidic mixer comprises a microfluidic flow channel structure and an irradiation window, wherein the microfluidic flow channel structure comprises a first sample injection flow channel, a second sample injection flow channel, a mixing flow channel, an output flow channel and an irradiation flow channel, the first sample injection flow channel and the second sample injection flow channel are respectively positioned at two sides of the mixing flow channel and are mutually communicated, the output flow channel is positioned below the mixing flow channel, the irradiation flow channel is positioned below the mixing flow channel, the output flow channel and the irradiation flow channel are mutually communicated, a mixed sample in the mixing flow channel enters the irradiation flow channel through the output flow channel, the irradiation window is correspondingly arranged with the irradiation flow channel, a beam of X-ray irradiates the irradiation flow channel from the irradiation window and is used for marking the mixed sample by hydroxyl radicals, the microfluidic mixer is formed by laminating a mixing layer, a sealing layer and a cover plate, the irradiation flow channel is arranged below the mixing layer, the sealing layer and the cover plate are mutually communicated, the mixed sample in the mixing flow channel enters the irradiation flow channel through the output flow channel, the first flow channel and the second flow channel is different in width from the first flow channel, and the first flow channel and the second flow channel is smaller than the first flow channel;
The double-channel injection pump comprises a first channel injection pump and a second channel injection pump, and the injection end of the first channel injection pump is connected with the first sample injection flow channel; the injection end of the second channel injection pump is connected with the second sample injection flow channel, and the first channel injection pump and the second channel injection pump respectively inject samples into the micro-flow channel structure;
The mobile platform is connected with the microfluidic mixer and is used for adjusting the position of the microfluidic mixer to realize that the beam center of X-rays is aligned with the irradiation window;
the control unit is respectively and electrically connected with the double-channel injection pump and the mobile platform;
The two window sealing layers are respectively arranged on two side surfaces of the mixing layer, and the window sealing layers have X-ray penetrability and are used for sealing the micro-channel structure;
The sealing layers comprise a first sealing layer and a second sealing layer, and the first sealing layer and the second sealing layer are respectively positioned on one surface of the two window sealing layers, which is far away from the mixed layer;
The cover plate layer comprises a first cover plate and a second cover plate, the first cover plate is positioned on one surface of the first sealing layer, which is far away from the mixed layer, and the second cover plate is positioned on one surface of the second sealing layer, which is far away from the mixed layer;
The first cover plate, the first sealing layer and the window sealing layer adjacent to the first sealing layer are all communicated and provided with a first sample inlet, a second sample inlet and a sample outlet, the first sample inlet is communicated with the first sample inlet flow channel, the second sample inlet is communicated with the second sample inlet flow channel, the sample outlet is positioned below the irradiation window and communicated with the irradiation flow channel, and a sample marked by hydroxyl radical irradiation is led out from the sample outlet;
The width of the irradiation flow channel is 0.25 mm-0.3 mm.
2. The X-ray based hydroxyl radical irradiation marking device according to claim 1, wherein the window sealing layer is made of polyimide film.
3. The X-ray based hydroxyl radical irradiation marking device according to claim 1, wherein the microfluidic mixer is made of stainless steel, and the micro-channel structure is formed by laser etching.
4. The X-ray based hydroxyl radical irradiation marking device according to claim 1, wherein the moving platform is a two-dimensional moving platform, the two-dimensional moving platform comprises a horizontal position adjusting module and a vertical position adjusting module, the horizontal position adjusting module is used for adjusting the movement of the microfluidic mixer in the horizontal direction, and the vertical position adjusting module is used for adjusting the movement of the microfluidic mixer in the vertical direction so as to align the irradiation window with the beam center of the X-rays.
5. The X-ray based hydroxyl radical irradiation marking device according to claim 4, wherein the horizontal position adjusting module comprises a horizontal base, a horizontal screw rod, a horizontal sliding block and a horizontal stepping motor;
The horizontal lead screw is fixedly arranged on the horizontal base along the horizontal direction, the horizontal sliding block is arranged on the horizontal lead screw, the microfluidic mixer is fixedly connected with the horizontal sliding block, the horizontal stepping motor is connected with the horizontal lead screw, and the horizontal stepping motor drives the horizontal sliding block to move in the horizontal direction through the horizontal lead screw, so that the microfluidic mixer is driven to move in the horizontal direction.
6. The X-ray based hydroxyl radical irradiation marking device according to claim 5, wherein the vertical position adjustment module comprises a vertical base, a vertical screw, a vertical slider and a vertical stepper motor;
The vertical lead screw is arranged on the vertical base along the vertical direction, the vertical sliding block is arranged on the vertical lead screw, the vertical sliding block is fixedly connected with the horizontal base, the vertical stepping motor is connected with the vertical lead screw, the vertical stepping motor drives the vertical sliding block to move in the vertical direction through the vertical lead screw, and then the vertical sliding block drives the horizontal sliding block to move in the vertical direction through the horizontal base.
7. The X-ray based hydroxyl radical irradiation marking device according to claim 5, wherein a supporting rod is fixed below the horizontal sliding block, and the microfluidic mixer is fixedly connected below the horizontal sliding block through the supporting rod.
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| CN105665046A (en) * | 2016-03-01 | 2016-06-15 | 中国科学院上海应用物理研究所 | Fast-temperature-rise microfluidic chip system |
| CN115193352A (en) * | 2022-02-22 | 2022-10-18 | 天津大学 | Efficient micro mixer for nanoparticle synthesis based on inertia and acoustic wave effects |
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| EP3116651B1 (en) * | 2014-03-11 | 2020-04-22 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making it |
| CN109622083A (en) * | 2019-01-24 | 2019-04-16 | 京东方科技集团股份有限公司 | A kind of microfluidic system and preparation method thereof |
| CN110308295B (en) * | 2019-07-04 | 2024-01-26 | 浙江扬清芯片技术有限公司 | Microfluidic multichannel sample injection and cleaning device with same and cleaning method |
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| CN115193352A (en) * | 2022-02-22 | 2022-10-18 | 天津大学 | Efficient micro mixer for nanoparticle synthesis based on inertia and acoustic wave effects |
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