Auxiliary equipment for optical tweezers experiment and experiment method and cleaning method using auxiliary equipment

By designing auxiliary equipment for optical tweezers experiments, using a microfluidic chip and laser device combined with a sample memory and a sample injection module, the problem of low automation in the prior art is solved, and efficient experimental operations and result acquisition is achieved.

CN119757778AActive Publication Date: 2025-04-04TSINGHUA UNIVERSITY
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Patent Information

Application Number
CN202411883014.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-19
Publication Date
2025-04-04
Estimated Expiration
2044-12-19

AI Technical Summary

Technical Problem

The existing optical tweezer experimental equipment has low degree of automation and low efficiency, which affects work efficiency.

Method used

Design an auxiliary device, including a sample memory and a sample injection module, conduct single-molecular experiments through a microfluidic chip and laser device, and use the first switching valve to achieve rapid adjustment of the sample and concentration adjustment, thereby improving experimental efficiency.

Benefits of technology

The automation of optical tweezers experiments is realized, the experiment completion efficiency is improved, and the time and error rate of manual operation are reduced.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention discloses auxiliary equipment for an optical tweezers experiment and an experiment method and a cleaning method using the auxiliary equipment. The auxiliary device for the optical tweezers experiment comprises a sample storage device used for placing a plurality of sample containers; the sample injection module comprises at least two sampling control assemblies, the sampling control assemblies and the channels are arranged in a one-to-one correspondence mode, one end of each sampling control assembly is used for being connected with at least one sample container, and the other end of each sampling control assembly is used for being connected with a circulation inlet of the corresponding channel; a sampling control valve is arranged at one end of the connecting channel of each sampling control assembly. At least one sampling control assembly further comprises a first switching valve, the first switching valve comprises a first output port and at least two first input ports, the first output port is connected with the sampling control valve through an output connecting pipe, and each first input port is connected with one sample container through an input connecting pipe. The input connecting pipe and the output connecting pipe are capillary pipes. And by arranging the first switching valve which can be switched, the experiment completion efficiency is greatly improved.
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Description

Technical Field

[0001] The invention relates to the field of biochemical experimental equipment, and in particular to auxiliary equipment used for optical tweezers experiments and an experimental method and a cleaning method using the auxiliary equipment. Background Art

[0002] In the optical tweezers experiments in the fields of biology, chemistry, and medicine, the experimental process and the cleaning process need to be controlled very finely. In the existing technology, the experimenters have to do the manual work, which has a low degree of automation and extremely low efficiency, affecting the work efficiency. Summary of the invention

[0003] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides an auxiliary device for optical tweezers experiments, which can improve the efficiency of experimental completion.

[0004] The present invention proposes an experimental method and a cleaning method using the auxiliary equipment for optical tweezers experiments.

[0005] According to the auxiliary equipment for optical tweezers experiment of the first aspect of the embodiment of the present invention, the optical tweezers experiment performs single-molecule experiments through a microfluidic chip and a laser device, and the microfluidic chip is provided with at least two channels, each of which has a flow inlet. The auxiliary equipment for optical tweezers experiment includes: a sample storage device for placing multiple sample containers, each of which is used to store samples; an injection module, the injection module includes at least two sampling control components, the sampling control components are arranged in a one-to-one correspondence with the channels, one end of each of the sampling control components is used to connect to at least one of the sample containers, and the other end of each of the sampling control components is used to connect to the flow inlet of the channel, and a sampling control valve is provided at one end of each of the sampling control components connected to the channel.

[0006] Among them, at least one of the sampling control components also includes: a first switching valve, the first switching valve includes a first output port and at least two first input ports, the first output port is connected to the sampling control valve through an output connecting pipe, each of the first input ports is connected to a sample container through an input connecting pipe, and the first switching valve can switchably control one of the first input ports to be connected to the first output port; wherein the input connecting pipe and the output connecting pipe are both capillaries.

[0007] According to the auxiliary equipment for optical tweezers experiments in the first aspect of the embodiment of the present invention, by providing a first switching valve that can switch the input source, when the concentration, composition or dosage of the sample needs to be adjusted, it can be achieved directly by switching the first switching valve, thereby greatly improving the efficiency of completing the experiment.

[0008] In some embodiments, the sample storage device comprises: a storage tank, the storage tank is used to hold a storage liquid, and the sample container can be placed in the storage tank; an adjustment device, the adjustment device is connected to the storage tank to adjust the state of the storage liquid and the sample; the adjustment device comprises: at least one of an ultrasonic generator and a constant temperature maintaining device, the ultrasonic generator is used to generate ultrasonic waves to the storage liquid to shake the sample, and the constant temperature maintaining device is used to keep the storage liquid and the sample at a set temperature.

[0009] Specifically, the adjustment device includes a constant temperature maintaining device, which includes: a refrigeration container, which is connected to the storage tank through a displacement tube; a displacement pump, which is arranged on the displacement tube to drive the stored liquid in the displacement tube to flow when started, and make the stored liquid in the refrigeration container and the storage tank flow through the displacement tube; a temperature detection component, which is used to detect the temperature in the storage tank, and the detection result of the temperature detection component is used to at least control the switch of the displacement pump.

[0010] In some embodiments, the auxiliary equipment for optical tweezers experiments also includes: a cleaning module for cleaning the sampling control component and / or the sample container, the cleaning module includes: a second switching valve; the second switching valve includes: a second output port and at least two second input ports, the second output port is used to connect the sample container or the input connecting tube, each second input port is used to connect a cleaning container containing a cleaning reagent, and at least two of the cleaning containers contain cleaning reagents of different types; the second switching valve can switchably control one of the second input ports to be connected to the second output port.

[0011] Specifically, the cleaning module further includes: a liquid separation box, wherein a liquid separation cavity is provided in the liquid separation box, and a liquid inlet and a plurality of liquid separation ports are correspondingly provided, wherein the liquid inlet is connected to the second output port, and the plurality of liquid separation ports are used to connect to the sample container or the input connecting tube.

[0012] Further, there are two liquid separation chambers, namely the first liquid separation chamber and the second liquid separation chamber; the liquid inlet includes a first liquid inlet and a second liquid inlet, the first liquid inlet is connected to the first liquid separation chamber, and the second liquid inlet is connected to the second liquid separation chamber; the multiple liquid separation ports include multiple first liquid separation ports and multiple second liquid separation ports, multiple first liquid separation ports are connected to the first liquid separation chamber, multiple second liquid separation ports are connected to the second liquid separation chamber, the first liquid separation port is used to connect the input connecting tube, and the second liquid separation port is used to connect the sample container.

[0013] The cleaning module also includes: a third switching valve; the third switching valve includes: a third input port and two third output ports, the third input port is connected to the second output port, the two third output ports are respectively connected to the first liquid inlet and the second liquid inlet, and the third switching valve can switchably control the third input port to be connected to one of the third output ports.

[0014] Specifically, the cleaning module further includes: a first air pressure control valve, the output end of the first air pressure control valve is connected to the liquid separation chamber, and the input end of the first air pressure control valve is used to connect to a driving air source.

[0015] According to the experimental method of the auxiliary equipment for optical tweezers experiment in the second aspect of the embodiment of the present invention, at least one of the sampling control components is connected to a plurality of the sample containers through the first switching valve.

[0016] The experimental steps are:

[0017] Opening a plurality of the sampling control components to allow a plurality of the samples to flow into a plurality of the channels correspondingly, wherein the first switching valve connects the first output port with one of the first input ports;

[0018] When the first laser beam and the second laser beam emitted by the laser device pull the single molecules of two of the channels closer together and then away from each other, the experimental phenomenon and the measurement result are obtained;

[0019] And when the number of the measurement results obtained reaches a set number of times, or when the experimental phenomenon does not meet the first set condition, or when the measurement result exceeds the first set range, control at least one of the first switching valves to connect the first output port with another first input port to adjust the composition, concentration or dosage of the sample passed into the corresponding channel.

[0020] According to the experimental method of the auxiliary device for optical tweezers experiment in the third aspect of the present invention, the experimental steps are:

[0021] Opening a plurality of the sampling control components to allow a plurality of the samples to flow into a plurality of the channels correspondingly, wherein the first switching valve connects the first output port with one of the first input ports;

[0022] When the first laser beam and the second laser beam emitted by the laser device pull the single molecules of two of the channels closer together and then away from each other, the experimental phenomenon and the measurement result are obtained;

[0023] When the experimental phenomenon does not satisfy the second set condition, or when the measurement result exceeds the second set range, the adjustment device is controlled to start so as to adjust the state of the sample.

[0024] According to the cleaning method of the auxiliary equipment for optical tweezers experiment in the fourth aspect of the present invention, the cleaning step comprises:

[0025] After the first switching valve connects the first output port with one of the first input ports, the second output port of the second switching valve connects with one of the second input ports, driving the cleaning reagent in the corresponding cleaning container into the liquid separation box through the second switching valve, and then driving the cleaning reagent into the sampling control component or the sample container;

[0026] Then, at least one of the first switching valve and the second switching valve is switched to make the first output port communicate with another first input port, and / or the second output port communicate with another second input port;

[0027] This cycle is repeated until the following conditions are met: each of the capillaries completes at least one cleaning cycle;

[0028] In one cleaning cycle, all kinds of cleaning agents flow through the capillary in chronological order.

[0029] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0031] Figure 1 A diagram showing the module composition of an auxiliary device for optical tweezers experiments according to an embodiment of the present invention;

[0032] Figure 2 A physical picture of auxiliary equipment used for optical tweezers experiments in some embodiments of the present invention;

[0033] Figure 3 A structural diagram of an auxiliary device used for optical tweezers experiments in some embodiments of the present invention;

[0034] Figure 4 A diagram showing the coordination relationship between auxiliary equipment used for optical tweezers experiments and a sample storage device in some embodiments of the present invention;

[0035] Figure 5 A simplified structural diagram of an auxiliary device for optical tweezers experiments in a cleaning module in some embodiments of the present invention;

[0036] Figure 6 A physical diagram of a cleaning module in some embodiments of the present invention;

[0037] Figure 7 for Figure 6 Three other connection state diagrams of the second switching valve in the cleaning module are shown.

[0038] Reference numerals:

[0039] Auxiliary equipment for optical tweezers experiments 1000,

[0040] Microfluidic chip 100, channel 1, flow inlet 101, flow outlet 102,

[0041] Laser device 200,

[0042] Sample storage 300,

[0043] Storage tank 310,

[0044] Adjustment device 320, ultrasonic generator 321, constant temperature holding device 322, refrigeration container 3221, semiconductor refrigerator 3222, radiator 3223, displacement pump 3224, temperature detection element 3225, displacement tube 3226,

[0045] Sample tube rack 330

[0046] Injection module 400,

[0047] Sampling control component 4,

[0048] The first switching valve 410, the first output port 411, the first input port 412,

[0049] Output connection pipe 420,

[0050] Input connection pipe 430,

[0051] Sampling control valve 440,

[0052] Cleaning module 500,

[0053] The second switching valve 510, the second output port 511, the second input port 512,

[0054] Liquid separation box 520,

[0055] The liquid separation chamber 5201, the first liquid separation chamber 5201-1, and the second liquid separation chamber 5201-2,

[0056] Liquid inlet 5202, first liquid inlet 5202-1, second liquid inlet 5202-2,

[0057] The liquid dispensing port 5203, the first liquid dispensing port 5203-1, the second liquid dispensing port 5203-2,

[0058] Screw-on buckle 5204,

[0059] Plug 5205,

[0060] The third switching valve 540, the third output port 541, the third input port 542,

[0061] The first air pressure control valve 550,

[0062] Fixed seat 560, through port 561,

[0063] Support frame 570,

[0064] Sample container 610, connecting ear 611, cleaning container 620,

[0065] Driving gas source 710, DETAILED DESCRIPTION

[0066] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0067] In the description of the present invention, it should be understood that the terms "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention. In addition, features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, "plurality" means two or more.

[0068] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be connected, or indirectly connected through an intermediate medium, or it can be internal communication between two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0069] The structure of an auxiliary device 1000 for an optical tweezers experiment according to an embodiment of the present invention, as well as an experimental method and a cleaning method based on the auxiliary device 1000 for an optical tweezers experiment are described below with reference to the accompanying drawings.

[0070] like Figure 1As shown, the auxiliary equipment 1000 for the optical tweezers experiment involved in the completion of the optical tweezers experiment requires not only the experimental equipment itself, but also the participation of the automation control module and the experimental result analysis module behind it. In order to facilitate cleaning, the design of the cleaning module 500 is also added. Of course, this application is currently based on the structural modification of the hardware part of the auxiliary equipment 1000 for the optical tweezers experiment, and the modification of the software part is not included in the present application scheme.

[0071] The auxiliary device 1000 for optical tweezers experiment according to the first aspect of the present invention is as follows: Figure 2 and Figure 3 As shown, the optical tweezers experiment performs a single molecule experiment through a microfluidic chip 100 and a laser device 200 . The microfluidic chip 100 is provided with at least two channels 1 , and each channel 1 has a flow inlet 101 .

[0072] The auxiliary equipment 1000 for optical tweezers experiment includes: a sample storage 300 and a sampling module 400. The sample storage 300 is used to place multiple sample containers 610, each of which is used to store samples. The sampling module 400 includes at least two sampling control components 4, and the sampling control components 4 are arranged one by one with the channel 1. One end of each sampling control component 4 is used to connect at least one sample container 610, and the other end of each sampling control component 4 is used to connect to the flow inlet 101 of the channel 1. A sampling control valve 440 is provided at one end of each sampling control component 4 connected to the channel 1.

[0073] Of course, after the sampling control valve 440 is opened, the driving gas source 710 will be connected to the sample container 610 to pump the sample in the sample container 610 to the sampling control component 4 until it is sent to the channel 1 of the microfluidic chip 100. Here, the connection method between the driving gas source 710 and the sample container 610 is not limited, for example, Figure 2 In the embodiment, the sample container 610 is provided with an air inlet, which is connected to the driving air source 710. Of course, the driving air source 710 can be connected to multiple sample containers 610, and the air pressure in each sample container 610 can be precisely controlled by valve control. Since the driving air source 710 can pump the sample in the sample container 610 using the existing technical solution, it will not be described in detail here.

[0074] Among them, at least one sampling control component 4 also includes: a first switching valve 410, the first switching valve 410 includes a first output port 411 and at least two first input ports 412, the first output port 411 is connected to the sampling control valve 440 through the output connecting pipe 420, and each first input port 412 is connected to a sample container 610 through the input connecting pipe 430. The first switching valve 410 can switchably control one of the first input ports 412 to be connected to the first output port 411.

[0075] Specifically, the optical tweezers experiment is an experimental device that uses the mechanical effect of light, such as focusing a laser beam to form optical tweezers, to capture, manipulate and study tiny particles. The fluid used to transport tiny particles in the experiment is a sample solution. In order to accurately control the flow rate, in this application, both the input connecting tube 430 and the output connecting tube 420 are capillaries.

[0076] In this way, in the auxiliary equipment 1000 for optical tweezers experiments of the present application, by setting at least two samples and by setting a switchable first switching valve 410, the first switching valve 410 can be switched when needed to achieve replacement of samples in the same channel 1 of the microfluidic chip 100, thereby greatly improving the efficiency of completing the experiment.

[0077] Here, the sample components contained in the at least two sample containers 610 connected by the first switching valve 410 may be the same or different. When the sample components contained in the at least two sample containers 610 are different, at least one component of the sample may be different, or the ratio (i.e., concentration) of at least one component may be different.

[0078] In some embodiments, Figure 3 and Figure 4 As shown, the sample storage 300 includes: a storage tank 310 and an adjustment device 320. The storage tank 310 is used to hold the storage liquid, and the sample container 610 can be placed in the storage tank 310. The adjustment device 320 is connected to the storage tank 310 to adjust the state of the storage liquid and the sample. In this way, when the sample precipitates, the activity of the sample can be improved by starting the adjustment device 320, thereby improving the success rate of the experiment.

[0079] Reference Figure 4 In some specific embodiments, the adjusting device 320 includes: an ultrasonic generator 321, which is used to generate ultrasonic waves to the storage liquid to shake the sample. Here, the ultrasonic generator 321 can adopt the structure of an ultrasonic generator known in the prior art, and its structure and principle are not repeated here.

[0080] Specifically, ultrasound can break down the precipitated molecular clusters into smaller particles through the high shear force generated by its cavitation effect, making them easier to disperse in the solvent to form a uniform suspension or solution. This improves the experimental effectiveness in subsequent optical tweezer experiments.

[0081] In some specific embodiments, the adjustment device 320 includes: a constant temperature holding device 322. The constant temperature holding device 322 is used to keep the storage liquid and the sample at a set temperature. It is understandable that temperature is a key factor affecting the experimental results. If the temperature is inconsistent under different experimental conditions, it is difficult to obtain the same experimental results even if other experimental conditions are the same. Therefore, treating the sample at a constant temperature helps to maintain the consistency of the experimental conditions and improve the reliability of the experimental results.

[0082] In some specific embodiments, referring to Figure 4 The adjustment device 320 includes a constant temperature maintaining device 322 , and the constant temperature maintaining device 322 includes: a refrigeration container 3221 , a displacement pump 3224 and a temperature detection component 3225 .

[0083] The refrigeration container 3221 is connected to the storage tank 310 via a displacement pipe 3226. The displacement pump 3224 is disposed on the displacement pipe 3226 to drive the stored liquid in the displacement pipe 3226 to flow when started, and to make the stored liquid in the refrigeration container 3221 and the storage tank 310 flow through the displacement pipe 3226. The temperature detection element 3225 is used to detect the temperature in the storage tank 310, and the detection result of the temperature detection element 3225 is used to control at least the switch of the displacement pump 3224.

[0084] It is understandable that the temperature in the storage tank 310 is the storage temperature of the sample, so the sample temperature can be controlled in real time, the sample temperature can be automatically maintained, and unnecessary energy consumption can be reduced.

[0085] Specifically, the adjustment device 320 further includes: a semiconductor refrigerator 3222, the cold end of the semiconductor refrigerator 3222 is connected to the refrigeration container 3221, and the hot end of the semiconductor refrigerator 3222 is used for heat dissipation, so that the heat of the refrigeration container 3221 can be quickly output and dispersed.

[0086] Furthermore, the adjustment device 320 further includes: a heat sink 3223, and the heat sink 3223 is arranged at the hot end of the semiconductor cooler 3222, so as to improve the heat dissipation efficiency.

[0087] In some embodiments, Figure 4 As shown, the sample container 610 is a sample test tube, which occupies less area. In particular, the sample test tube can also be a large-capacity test tube.

[0088] Specifically, Figure 4 As shown, the sample storage 300 further includes: a sample test tube rack 330, which is set above the storage tank 310, and the sample test tubes can be placed on the sample test tube rack 330, which can improve neatness and orderliness and facilitate identification.

[0089] In some embodiments, Figure 3As shown, the auxiliary device 1000 for optical tweezers experiment also includes: a cleaning module 500, which is used to clean the sampling control component 4 or the sample container 610. Therefore, the sample container 610 can be connected to the sampling control component 4, so the cleaning module 500 can also clean the sample container 610 at the same time.

[0090] It is understandable that since the input connecting tube 430 and the output connecting tube 420 in the sampling control component 4 are both capillaries, cleaning the capillaries in conventional experiments requires manual processing, which is extremely time-consuming and difficult to standardize. In this application, the cleaning module 500 is used to clean the capillaries, which realizes automatic cleaning, not only saves manual time, but also improves cleaning standardization.

[0091] Reference Figure 5 and Figure 6 The cleaning module 500 includes: a second switching valve 510. The second switching valve 510 includes: a second output port 511 and at least two second input ports 512. The second output port 511 is used to connect the sample container 610 or the input connecting pipe 430. Each second input port 512 is used to connect the cleaning container 620 containing cleaning reagents. The types of cleaning reagents contained in at least two cleaning containers 620 are different. The second switching valve 510 can switchably control one of the second input ports 512 to be connected to the second output port 511. This arrangement allows different cleaning reagents to be cleaned in an orderly manner.

[0092] When the second output port 511 is connected to the input connection pipe 430, the sampling control component 4 is opened, and the cleaning reagent flows through the entire sampling control component 4 and enters the channel 1 for cleaning. At this time, the channel 1 can also be cleaned.

[0093] When the second output port 511 is connected to the sample container 610, the sampling control component 4 is opened, and the cleaning reagent flows through the sample container 610, the entire sampling control component 4 and enters the channel 1 for cleaning.

[0094] Here, taking the second switching valve 510 having three second input ports 512 as an example, it can have four states. Figure 5 A connection state shown, also as Figure 7 The two connection states shown in (a) and (b) are also shown in Figure 7 The closed state shown in (c) in FIG. 1 , that is, the second switching valve 510 is closed.

[0095] Specifically, the cleaning module 500 further includes: a liquid separation box 520, a liquid separation chamber 5201 is provided in the liquid separation box 520, and a liquid inlet 5202 and a plurality of liquid separation ports 5203 are correspondingly provided, the liquid inlet 5202 is connected to the second output port 511, and the plurality of liquid separation ports 5203 are used to connect the sample container 610 or the input connecting tube 430. It can be understood that the sampling control component 4 and the cleaning sample container 610 used in the experiment are multiple, and the liquid separation box 520 is used to divide the cleaning reagent into multiple paths to connect the sampling control component 4 and the cleaning sample container 610, which can improve the cleaning efficiency.

[0096] Further, there are two liquid separation chambers 5201, which are respectively a first liquid separation chamber 5201-1 and a second liquid separation chamber 5201-2. The liquid inlet 5202 includes a first liquid inlet 5202-1 and a second liquid inlet 5202-2, the first liquid inlet 5202-1 is connected to the first liquid separation chamber 5201-1, and the second liquid inlet 5202-2 is connected to the second liquid separation chamber 5201-2. The plurality of liquid separation ports 5203 include a plurality of first liquid separation ports 5203-1 and a plurality of second liquid separation ports 5203-2, the plurality of first liquid separation ports 5203-1 are connected to the first liquid separation chamber 5201-1, the plurality of second liquid separation ports 5203-2 are connected to the second liquid separation chamber 5201-2, the first liquid separation port 5203-1 is used to connect to the input connecting tube 430, and the second liquid separation port 5203-2 is used to connect to the sample container 610.

[0097] The cleaning module 500 further includes: a third switching valve 540. The third switching valve 540 includes: a third input port 542 and two third output ports 541, the third input port 542 is connected to the second output port 511, the two third output ports 541 are respectively connected to the first liquid inlet 5202-1 and the second liquid inlet 5202-2, and the third switching valve 540 can switchably control the third input port 542 to be connected to one of the third output ports 541.

[0098] With such arrangement, the user can select the sampling control component 4 and the cleaning sample container 610 as required, thereby improving the selection autonomy.

[0099] Specifically, the cleaning module 500 further includes: a first air pressure control valve 550, the output end of the first air pressure control valve 550 is connected to the liquid separation chamber 5201, and the input end of the first air pressure control valve 550 is used to connect to the driving gas source. In this way, when the cleaning reagent is separated in the liquid separation box 520, by opening the first air pressure control valve 550, the gas pumps the cleaning reagent to the sampling control component 4 or the cleaning sample container 610. In this way, the flow rate of the cleaning reagent is increased and the cleaning efficiency is improved.

[0100] In some specific embodiments, Figure 5 and Figure 6As shown, a screw-on buckle 5204 is formed at each second liquid dispensing port 5203-2, and a connecting ear 611 is provided on the sample container 610, and the connecting ear 611 can be screwed on the screw-on buckle 5204 by rotation. In this way, the connection efficiency of the sample container 610 can be improved.

[0101] Specifically, the screw-on buckle 5204 is two clamping plates, which are arranged circumferentially, and a notch is provided between the two ends of the two clamping plates. There are two connecting ears 611 on the top of the sample container 610. When installed, the two connecting ears 611 are directly opposite to the two notches, and are inserted upward to open the top of the sample container 610 and plug into the second liquid dispensing port 5203-2. Then, the sample container 610 is rotated so that the two connecting ears 611 are stuck on the top of the two clamping plates.

[0102] Furthermore, the cleaning module 500 further includes a plug 5205 for blocking the first liquid separation port 5203-1 and the second liquid separation port 5203-2, so that the unused first liquid separation port 5203-1 and the second liquid separation port 5203-2 can be blocked.

[0103] In some embodiments, Figure 5 As shown, the cleaning module 500 further includes: a fixing seat 560 and a support frame 570, and the second switching valve 510 is mounted on the fixing seat 560. The support frame 570 is mounted on the fixing seat 560, and the liquid separation box 520 is rotatably mounted on the support frame 570 to facilitate adjusting the position of the liquid separation port 5203.

[0104] The fixing base 560 is a basic supporting structure and may be box-shaped to conveniently accommodate various components.

[0105] The liquid separation box 520 is rotatably mounted on the support frame 570, and the direction of the liquid separation port 5203 can be adjusted. When installing and removing the sampling control component 4 and cleaning the sample container 610, the liquid separation port 5203 can be tilted outward or placed horizontally. After the sampling control component 4 and the sample container 610 are installed, the liquid separation port 5203 can be set downward.

[0106] Specifically, the fixing seat 560 is a box body with one horizontal side open, so as to facilitate manual installation of the sampling control component 4 and the cleaning sample container 610 onto the liquid separation box 520 .

[0107] Specifically, the support frame 570 is a frame, and the liquid separation box 520 is rotatably connected to the top of the support frame 570. The second switching valve 510 is located above the support frame 570.

[0108] Furthermore, a through opening 561 is formed on one side of the fixing seat 560 , and the cleaning container 620 is used to be placed outside the fixing seat 560 , and is connected to the second switching valve 510 through a pipeline passing through the through opening.

[0109] According to the experimental method of the auxiliary device 1000 for optical tweezers experiment in the second aspect of the embodiment of the present invention, at least one sampling control component 4 is connected to multiple sample containers 610 through a first switching valve 410. Here, the samples contained in the multiple sample containers 610 can be of the same composition. For example, when the sample in one sample container 610 is not enough, at least two sample containers 610 can be prepared to contain samples of the same composition. In the multiple sample containers 610 connected to the same first switching valve 410, the sample compositions can also be different, for example, at least one component of the sample can be different, or the ratio (i.e., concentration) of at least one component can be different.

[0110] The experimental steps of the auxiliary device 1000 for optical tweezers experiment are:

[0111] The plurality of sampling control components 4 are opened to allow the plurality of samples to flow into the plurality of channels 1 correspondingly, wherein the first switching valve 410 connects the first output port 411 with one of the first input ports 412 .

[0112] When the first laser beam and the second laser beam emitted by the laser device 200 pull the single molecules in two channels 1 closer together and then away from each other, experimental phenomena and measurement results are obtained.

[0113] When the number of measurement results obtained reaches a set number of times, or when the experimental phenomenon does not meet the first set condition, or when the measurement result exceeds the first set range, at least one first switching valve 410 is controlled to connect the first output port 411 with another first input port 412 to adjust the composition, concentration or dosage of the sample passed into the corresponding channel 1.

[0114] In this way, the composition, concentration or dosage of the sample can be switched automatically during the experiment, thereby improving the experimental efficiency.

[0115] Here, the first setting condition can be set according to the specific experiment. For example, in the optical tweezers experiment, when the laser beam is projected onto a single molecule, the light spot generated by the single molecule needs to reach a preset brightness range, or the size of the light spot needs to reach a preset area range.

[0116] The first setting range can be specifically set according to a specific experiment. For example, if the measurement result of the optical tweezers experiment is a tension value, the first setting range is that the measurement result is within a predetermined tension value range.

[0117] According to the experimental method of the auxiliary device 1000 for optical tweezers experiment in the third aspect of the present invention, the experimental steps are:

[0118] Open the multiple sampling control components 4 to allow the multiple samples to flow into the multiple channels 1 accordingly, wherein the first switching valve 410 connects the first output port 411 with one of the first input ports 412;

[0119] When the first laser beam and the second laser beam emitted by the laser device 200 pull the single molecules in two channels 1 closer together and then away from each other, the experimental phenomenon and measurement results are obtained;

[0120] When the experimental phenomenon does not satisfy the second set condition, or when the measurement result exceeds the second set range, the control adjustment device 320 is started to adjust the state of the sample.

[0121] That is to say, if the sample state is not ideal during the experiment, the adjustment device 320 can be automatically controlled to start.

[0122] Here, the second setting condition can be set according to the specific experiment. For example, in the optical tweezers experiment, when the laser beam is projected onto a single molecule, the light spot generated by the single molecule needs to reach a preset brightness range, or the size of the light spot needs to reach a preset area range.

[0123] The second setting range can be specifically set according to the specific experiment. For example, if the measurement result of the optical tweezers experiment is a tension value, the second setting range is that the measurement result is within a predetermined tension value range.

[0124] According to the cleaning method of the auxiliary device 1000 for optical tweezers experiment of the fourth aspect of the present invention, the cleaning steps include:

[0125] After the first switching valve 410 connects the first output port 411 with one of the first input ports 412, the second output port 511 of the second switching valve 510 is connected with one of the second input ports 512, and the cleaning reagent in the corresponding cleaning container 620 is driven into the liquid separation box 520 through the second switching valve 510, and then the cleaning reagent is driven into the sampling control component 4 or the sample container 610.

[0126] Then, at least one of the first switching valve 410 and the second switching valve 510 is switched to make the first output port 411 communicate with another first input port 412, and / or the second output port 511 communicate with another second input port 512;

[0127] This cycle is repeated until the following conditions are met: each capillary tube completes at least one cleaning cycle;

[0128] In one cleaning cycle, all cleaning agents flow through the capillary in chronological order.

[0129] In this way, the cleaning efficiency can be improved, the time invested in manpower can be reduced, and the standardization and regularization of cleaning can be improved.

[0130] In a specific embodiment, Figure 5 As shown, there are three cleaning containers 620, which are respectively filled with acidic liquid, alkaline liquid and purified water.

[0131] Each capillary needs to complete at least one cleaning cycle, that is, the second switching valve 510 first switches to the second input port 512 connected to the acidic liquid and connected to the second output port 511, then switches to the second input port 512 connected to the alkaline liquid and connected to the second output port 511, and then switches to the second input port 512 connected to the clean water and connected to the second output port 511, and the capillary completes the cleaning process of first acidic liquid, then alkaline liquid, and then clean water. Alternatively, in a cleaning cycle, the second switching valve 510 first switches to the second input port 512 connected to the alkaline liquid and connected to the second output port 511, then switches to the second input port 512 connected to the acidic liquid and connected to the second output port 511, and then switches to the second input port 512 connected to the clean water and connected to the second output port 511, and the capillary completes the cleaning process of first alkaline liquid, then acidic liquid, and then clean water.

[0132] It is understandable that the same cleaning agent can be used multiple times when cleaning the same capillary. For example, a capillary must be cleaned in the order of acidic liquid, alkaline liquid, and finally purified water. In this case, there can be multiple cleaning sequences: 1) acid->base->water; 2) acid->base->water->acid->base->water; 3) acid->acid->base->water; 4) acid->base->base->water, etc.

[0133] In the description of this specification, the description with reference to the terms "embodiment", "example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0134] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. An auxiliary device for optical tweezers experiment, wherein the optical tweezers experiment performs a single molecule experiment through a microfluidic chip (100) and a laser device (200), wherein the microfluidic chip (100) is provided with at least two channels (1), each of the channels (1) having a flow inlet (101), characterized in that: The auxiliary equipment (1000) for optical tweezers experiment comprises: A sample storage (300) for accommodating a plurality of sample containers (610), each of the sample containers (610) being used for storing a sample; A sampling module (400), the sampling module (400) comprising at least two sampling control components (4), the sampling control components (4) being arranged in one-to-one correspondence with the channels (1), one end of each of the sampling control components (4) being used to connect to at least one of the sample containers (610), the other end of each of the sampling control components (4) being used to connect to the flow inlet (101) of the channel (1), and one end of each of the sampling control components (4) connected to the channel (1) being provided with a sampling control valve (440); Wherein, at least one of the sampling control components (4) further comprises: A first switching valve (410), the first switching valve (410) comprising a first output port (411) and at least two first input ports (412), the first output port (411) being connected to the sampling control valve (440) via an output connecting pipe (420), each of the first input ports (412) being connected to one of the sample containers (610) via an input connecting pipe (430), and the first switching valve (410) being capable of switchingly controlling one of the first input ports (412) to be connected to the first output port (411); Wherein, the input connecting pipe (430) and the output connecting pipe (420) are both capillaries.

2. The auxiliary device for optical tweezers experiment according to claim 1, characterized in that: The sample storage (300) comprises: A storage tank (310), wherein the storage tank (310) is used to contain a storage liquid, and the sample container (610) can be placed in the storage tank (310); An adjusting device (320), the adjusting device (320) being connected to the storage tank (310) to adjust the state of the storage liquid and the sample; The adjustment device (320) comprises: at least one of an ultrasonic generator (321) and a constant temperature holding device (322), wherein the ultrasonic generator (321) is used to generate ultrasonic waves to the storage liquid to shake the sample, and the constant temperature holding device (322) is used to keep the storage liquid and the sample at a set temperature.

3. The auxiliary device for optical tweezers experiment according to claim 2, characterized in that: The adjusting device (320) comprises a constant temperature maintaining device (322), and the constant temperature maintaining device (322) comprises: A refrigeration container (3221), wherein the refrigeration container (3221) is connected to the storage tank (310) via a displacement pipe (3226); a displacement pump (3224), the displacement pump (3224) being arranged on the displacement pipe (3226) so as to drive the stored liquid in the displacement pipe (3226) to flow when started, and to make the stored liquid in the refrigeration container (3221) and the storage tank (310) flow through the displacement pipe (3226); A temperature detection element (3225), wherein the temperature detection element (3225) is used to detect the temperature in the storage tank (310), and the detection result of the temperature detection element (3225) is used to at least control the switch of the replacement pump (3224).

4. The auxiliary device for optical tweezers experiment according to any one of claims 1 to 3, characterized in that: Also includes: A cleaning module (500) for cleaning the sampling control component (4) and / or the sample container (610), wherein the cleaning module (500) comprises: a second switching valve (510); The second switching valve (510) comprises: a second output port (511) and at least two second input ports (512), the second output port (511) being used to connect to the sample container (610) or the input connecting pipe (430), each second input port (512) being used to connect to a cleaning container (620) containing a cleaning reagent, and the cleaning reagents contained in at least two cleaning containers (620) are of different types; The second switching valve (510) can switchably control one of the second input ports (512) to communicate with the second output port (511).

5. The auxiliary device for optical tweezers experiment according to claim 4, characterized in that: The cleaning module (500) further comprises: A liquid separation box (520), wherein a liquid separation chamber (5201) is provided in the liquid separation box (520), and a liquid inlet (5202) and a plurality of liquid separation ports (5203) are correspondingly provided, wherein the liquid inlet (5202) is connected to the second output port (511), and the plurality of liquid separation ports (5203) are used to connect to the sample container (610) or the input connecting tube (430).

6. The auxiliary device for optical tweezers experiment according to claim 5, characterized in that: The number of the liquid separation chambers (5201) is two, namely a first liquid separation chamber (5201-1) and a second liquid separation chamber (5201-2); The liquid inlet (5202) comprises a first liquid inlet (5202-1) and a second liquid inlet (5202-2), wherein the first liquid inlet (5202-1) is connected to the first liquid separation chamber (5201-1), and the second liquid inlet (5202-2) is connected to the second liquid separation chamber (5201-2); The plurality of liquid separation ports (5203) include a plurality of first liquid separation ports (5203-1) and a plurality of second liquid separation ports (5203-2), wherein the plurality of first liquid separation ports (5203-1) are connected to the first liquid separation chamber (5201-1), and the plurality of second liquid separation ports (5203-2) are connected to the second liquid separation chamber (5201-2), wherein the first liquid separation ports (5203-1) are used to connect to the input connecting tube (430), and the second liquid separation ports (5203-2) are used to connect to the sample container (610); The cleaning module (500) further includes: a third switching valve (540); The third switching valve (540) comprises: a third input port (542) and two third output ports (541), wherein the third input port (542) is connected to the second output port (511), and the two third output ports (541) are respectively connected to the first liquid inlet (5202-1) and the second liquid inlet (5202-2), and the third switching valve (540) can switchably control the third input port (542) to be connected to one of the third output ports (541).

7. The auxiliary device for optical tweezers experiment according to claim 5, characterized in that: The cleaning module (500) further comprises: a first air pressure control valve (550), wherein an output end of the first air pressure control valve (550) is connected to the liquid separation chamber (5201), and an input end of the first air pressure control valve (550) is used to connect to a driving air source.

8. An experimental method using the auxiliary device for optical tweezers experiment according to any one of claims 1 to 7, characterized in that: At least one of the sampling control components (4) is connected to a plurality of the sample containers (610) via the first switching valve (410); The experimental steps are: Opening the plurality of sampling control components (4) to allow the plurality of samples to flow into the plurality of channels (1) correspondingly, wherein the first switching valve (410) connects the first output port (411) with one of the first input ports (412); When the first laser beam and the second laser beam emitted by the laser device (200) pull the single molecules in two of the channels (1) closer together and then away from each other, an experimental phenomenon and a measurement result are obtained; When the number of the measurement results obtained reaches a set number of times, or when the experimental phenomenon does not meet the first set condition, or when the measurement result exceeds the first set range, at least one of the first switching valves (410) is controlled to connect the first output port (411) with another first input port (412) to adjust the composition, concentration or dosage of the sample introduced into the corresponding channel (1).

9. An experimental method using the auxiliary device for optical tweezers experiment according to claim 2, characterized in that: The experimental steps are: Opening the plurality of sampling control components (4) to allow the plurality of samples to flow into the plurality of channels (1) correspondingly, wherein the first switching valve (410) connects the first output port (411) with one of the first input ports (412); When the first laser beam and the second laser beam emitted by the laser device (200) pull the single molecules in two of the channels (1) closer together and then away from each other, an experimental phenomenon and a measurement result are obtained; When the experimental phenomenon does not satisfy the second set condition, or when the measurement result exceeds the second set range, the adjustment device (320) is controlled to start so as to adjust the state of the sample.

10. A method for cleaning the auxiliary equipment for optical tweezers experiment according to any one of claims 4 to 7, characterized in that: The cleaning steps include: After the first switching valve (410) connects the first output port (411) with one of the first input ports (412), the second output port (511) of the second switching valve (510) is connected with one of the second input ports (512), driving the cleaning reagent in the corresponding cleaning container (620) to enter the liquid separation box (520) through the second switching valve (510), and then driving the cleaning reagent to enter the sampling control component (4) or the sample container (610); Then, at least one of the first switching valve (410) and the second switching valve (510) is switched to make the first output port (411) communicate with another first input port (412), and / or the second output port (511) communicate with another second input port (512); This cycle is repeated until the following conditions are met: each of the capillaries completes at least one cleaning cycle; In one cleaning cycle, all kinds of cleaning agents flow through the capillary in chronological order.

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