Auxiliary device for optical tweezer experiment and experimental method using the same, cleaning method

Abstract

The application discloses an auxiliary device for optical tweezers experiment and an experimental method and a cleaning method using the same. The auxiliary device for optical tweezers experiment comprises a sample storage for placing a plurality of sample containers; a sample inlet module, the sample inlet module comprising at least two sampling pipe control assemblies, the sampling pipe control assemblies being arranged in one-to-one correspondence with channels, one end of each sampling pipe control assembly being used for connecting at least one sample container, the other end of each sampling pipe control assembly being used for connecting a flow inlet of a channel, and one end of each sampling pipe control assembly connected with the channel being provided with a sampling control valve. At least one sampling pipe control assembly further comprises a first switching valve, the first switching valve comprising a first output port and at least two first input ports, the first output port being connected with the sampling control valve through an output connecting pipe, and each first input port being connected with one sample container through an input connecting pipe. The input connecting pipe and the output connecting pipe are capillary tubes. By arranging the switchable first switching valve, the experimental completion efficiency is greatly improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biochemical experiment equipment, in particular to an auxiliary device for optical tweezer experiment and an experimental method and a cleaning method using the same. BACKGROUND

[0002] The optical tweezer experiment involved in the fields of biology, chemistry and medicine needs very fine control in the experimental process and the cleaning process. In the prior art, the experiment is manually operated by the experimenters, and the automation degree is low, the efficiency is extremely low, and the work efficiency is affected. SUMMARY

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

[0004] The present application proposes an experimental method and a cleaning method using the above-mentioned auxiliary device for optical tweezer experiment.

[0005] According to the auxiliary device for optical tweezer experiment of the first aspect of the present application, the optical tweezer experiment is carried out by a single molecule experiment through a microfluidic chip and a laser device, the microfluidic chip is provided with at least two channels, each channel has a flow inlet, and the auxiliary device for optical tweezer experiment comprises: a sample storage for placing a plurality of sample containers, each sample container is used for storing a sample; a sample inlet module, the sample inlet module comprises at least two sample tube control assemblies, the sample tube control assemblies are arranged one by one corresponding to the channels, one end of each sample tube control assembly is used for connecting at least one sample container, the other end of each sample tube control assembly is used for connecting the flow inlet of the channel, and one end of each sample tube control assembly connected to the channel is provided with a sample control valve.

[0006] Among them, at least one sample tube 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 to the sample control valve through an output connecting pipe, each first input port 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 communicate with the first output port; wherein the input connecting pipe and the output connecting pipe are capillary tubes.

[0007] According to the auxiliary device for optical tweezer experiment of the first aspect of the present application, by setting the first switching valve which can switch the input source, when the sample needs to be adjusted in concentration or composition or dosage, it can be realized by directly switching the first switching valve, which greatly improves the experimental completion efficiency.

[0008] In some embodiments, the sample storage device comprises: a storage pool for containing a storage solution, the sample container being disposed in the storage pool; an adjusting device connected to the storage pool for adjusting the state of the storage solution and the sample, the adjusting device comprising at least one of an ultrasonic generator for generating ultrasonic waves to the storage solution to shake the sample and a constant temperature maintaining device for maintaining the storage solution and the sample at a set temperature.

[0009] In particular, the adjusting device comprises the constant temperature maintaining device, which comprises: a refrigeration container connected to the storage pool through a displacement pipe; a displacement pump disposed on the displacement pipe for driving the flow of the storage solution in the displacement pipe when activated, and causing the storage solution in the refrigeration container and the storage pool to flow through the displacement pipe; and a temperature detecting member for detecting the temperature in the storage pool, the detection result of the temperature detecting member being used to control at least the on-off of the displacement pump.

[0010] In some embodiments, the auxiliary device for the optical tweezer experiment further comprises a cleaning module for cleaning the sampling tube control assembly and / or the sample container, the cleaning module comprising: a second switching valve; the second switching valve comprising: a second output port and at least two second input ports, the second output port being used for connecting the sample container or connecting the input connecting pipe, each of the second input ports being used for connecting a cleaning container containing a cleaning reagent, at least two of the cleaning containers containing cleaning reagents of different types; the second switching valve being switchably controlled to communicate one of the second input ports with the second output port.

[0011] In particular, the cleaning module further comprises: a separation box, the separation box being provided with a separation cavity and a liquid inlet and a plurality of separation ports corresponding thereto, the liquid inlet being communicated with the second output port, and the plurality of separation ports being used for connecting the sample container or the input connecting pipe.

[0012] Further, the separation cavity is two and is a first separation cavity and a second separation cavity; the liquid inlet comprises a first liquid inlet and a second liquid inlet, the first liquid inlet being communicated with the first separation cavity, and the second liquid inlet being communicated with the second separation cavity; the plurality of separation ports comprises a plurality of first separation ports and a plurality of second separation ports, the plurality of first separation ports being communicated with the first separation cavity, and the plurality of second separation ports being communicated with the second separation cavity, the first separation ports being used for connecting the input connecting pipe, and the second separation ports being used for connecting the sample container.

[0013] The cleaning module further comprises a third switch valve, the third switch valve comprises a third input port and two third output ports, the third input port is connected with the second output port, and the two third output ports are respectively connected with the first liquid inlet and the second liquid inlet, and the third switch valve is switchably controlled to communicate the third input port with one of the third output ports.

[0014] Specifically, the cleaning module further comprises a first air pressure control valve, an output end of the first air pressure control valve is connected with the distribution cavity, and an input end of the first air pressure control valve is used to be connected with a driving gas source.

[0015] According to the experimental method of the auxiliary equipment for the optical tweezer experiment provided in the second aspect of the present application, at least one of the sampling control assemblies is connected with a plurality of sample containers through the first switch valve.

[0016] The experimental steps are as follows:

[0017] The plurality of sampling control assemblies are opened to allow a plurality of samples to flow into a plurality of channels correspondingly, wherein the first switch valve is controlled to communicate 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 in two of the channels to approach and then move away, an experimental phenomenon and a measurement result are obtained.

[0019] When the number of the measurement results obtained reaches a set number of times, or when the experimental phenomenon does not meet a first set condition, or when the measurement result exceeds a first set range, the first switch valve is controlled to communicate the first output port with another first input port, so as to adjust the composition, the concentration or the amount of the sample flowing into the corresponding channel.

[0020] According to the experimental method of the auxiliary equipment for the optical tweezer experiment provided in the third aspect of the present application, the experimental steps are as follows:

[0021] The plurality of sampling control assemblies are opened to allow a plurality of samples to flow into a plurality of channels correspondingly, wherein the first switch valve is controlled to communicate 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 in two of the channels to approach and then move away, an experimental phenomenon and a measurement result are obtained.

[0023] When the experimental phenomenon does not meet a second set condition, or when the measurement result exceeds a second set range, the adjustment device is controlled to be started to adjust the state of the sample.

[0024] The cleaning method of the auxiliary equipment for optical tweezer experiment according to the fourth aspect of the present application comprises:

[0025] After the first switch valve is switched to connect the first output port with one of the first input ports, the second switch valve is switched to connect the second output port with one of the second input ports, the cleaning reagent in the corresponding cleaning container is driven to enter the distribution box through the second switch valve, and then the cleaning reagent is driven to enter the sampling tube control assembly or the sample container;

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

[0027] The above steps are repeated until each of the capillaries completes at least one cleaning cycle.

[0028] In one cleaning cycle, the capillaries flow through all kinds of cleaning reagents in sequence.

[0029] Additional aspects and advantages of the present application will be in part apparent and in part pointed out hereinafter. BRIEF DESCRIPTION OF DRAWINGS

[0030] The above and / or additional aspects and advantages of the present application will become apparent and be readily appreciated from the following description, including the appended drawings.

[0031] Figure 1 A module composition diagram of the auxiliary equipment for optical tweezer experiment according to the present application;

[0032] Figure 2 A physical diagram of the auxiliary equipment for optical tweezer experiment according to some embodiments of the present application;

[0033] Figure 3 A structure composition diagram of the auxiliary equipment for optical tweezer experiment according to some embodiments of the present application;

[0034] Figure 4 A matching relationship diagram of the auxiliary equipment for optical tweezer experiment according to some embodiments of the present application at a sample storage;

[0035] Figure 5 A structure diagram of the auxiliary equipment for optical tweezer experiment according to some embodiments of the present application at a cleaning module;

[0036] Figure 6 A physical diagram of the cleaning module according to some embodiments of the present application;

[0037] Figure 7 Fig. 3 shows another three connection state diagrams of the second switching valve in the cleaning module. Figure 6

[0038] Reference signs:

[0039] auxiliary equipment 1000 for optical tweezer experiment,

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

[0041] laser device 200,

[0042] sample storage 300,

[0043] storage pool 310,

[0044] adjustment device 320, ultrasonic generator 321, constant temperature holding device 322, refrigeration container 3221, semiconductor refrigerator 3222, heat sink 3223, displacement pump 3224, temperature detection piece 3225, displacement tube 3226,

[0045] sample test tube rack 330

[0046] sample inlet module 400,

[0047] sampling pipe control assembly 4,

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

[0049] output connecting pipe 420,

[0050] input connecting pipe 430,

[0051] sampling control valve 440,

[0052] cleaning module 500,

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

[0054] separation box 520,

[0055] separation cavity 5201, first separation cavity 5201-1, and second separation cavity 5201-2,

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

[0057] separation outlet 5203, first separation outlet 5203-1, and second separation outlet 5203-2,

[0058] screw buckle 5204,

[0059] ​a plug 5205,

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

[0061] a first air pressure control valve 550,

[0062] a fixed seat 560, a through port 561,

[0063] a support frame 570,

[0064] a sample container 610, a connecting lug 611, a cleaning container 620,

[0065] a driving gas source 710, DETAILED DESCRIPTION

[0066] Embodiments of the present application are described below in detail with reference to the accompanying drawings, in which the same or similar components or components having the same or similar functions are denoted by the same or similar reference numerals throughout. The embodiments described below by reference to the accompanying drawings are exemplary and are intended only to explain the present application, and should not be construed as limiting the present application.

[0067] In the description of the present application, it should be understood that the terms "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore should not be construed as limiting the present application. In addition, features defined with "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, unless otherwise specified, the meaning of "a plurality of" is two or more.

[0068] In the description of the present application, it should be noted that unless otherwise specified and limited, the terms "mounting", "connecting", "connecting" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be connected, or it can be indirectly connected through an intermediate medium, or it can be connected inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0069] The structure of the auxiliary equipment 1000 for optical tweezer experiment according to the embodiments of the present application is described below with reference to the accompanying drawings, as well as the experimental method and cleaning method extended based on the auxiliary equipment 1000 for optical tweezer experiment.

[0070] As Figure 1As shown, the light tweezers experiment involves the auxiliary equipment 1000 for the light tweezers experiment when the experiment is completed, not only the experimental equipment itself, but also the participation of the behind automatic control module and the experimental result analysis module. In order to facilitate cleaning, a cleaning module 500 is newly designed. Of course, the present application is based on the structural modification of the hardware part of the auxiliary equipment 1000 for the light tweezers experiment, and the modification of the software part is not included in the present application scheme.

[0071] According to the auxiliary equipment 1000 for the light tweezers experiment of the first aspect of the present application, as shown in Figure 2 and Figure 3 As shown, the light tweezers experiment is carried out by the single molecule experiment of the microfluidic chip 100 and the 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 the light tweezers experiment comprises a sample storage 300 and a sample injection module 400. The sample storage 300 is used to place a plurality of sample containers 610, and each sample container 610 is used to store a sample. The sample injection module 400 comprises at least two sampling pipe control assemblies 4, the sampling pipe control assemblies 4 are arranged one by one with the channels 1, one end of each sampling pipe control assembly 4 is used to connect at least one sample container 610, the other end of each sampling pipe control assembly 4 is used to connect the flow inlet 101 of the channel 1, and the end of each sampling pipe control assembly 4 connected with the channel 1 is provided with a sampling control valve 440.

[0073] Of course, after the sampling control valve 440 is opened, a driving gas source 710 is connected with the sample container 610 to pump the sample in the sample container 610 to the sampling pipe control assembly 4 until it is sent to the channel 1 of the microfluidic chip 100. Here, the connection mode of the driving gas source 710 with the sample container 610 is not limited, for example, in Figure 2 the sample container 610 is provided with a gas inlet connected with the driving gas source 710. Of course, the driving gas source 710 can be connected with a plurality of sample containers 610, and at this time, the accurate control of the gas pressure in each sample container 610 can be realized through the valve control. Since how the driving gas source 710 pumps the sample in the sample container 610 can adopt the prior art scheme, it is not described in detail here.

[0074] Among them, at least one sampling pipe control assembly 4 further comprises a first switching valve 410, the first switching valve 410 comprises a first output port 411 and at least two first input ports 412, the first output port 411 is connected with the sampling control valve 440 through an output connecting pipe 420, each first input port 412 is connected with a sample container 610 through an input connecting pipe 430, and the first switching valve 410 can be switched to control one of the first input ports 412 to communicate with the first output port 411.

[0075] Specifically, the optical tweezer experiment is an experimental device for capturing, manipulating and studying micro-particles by using the mechanical effect of light, such as focusing a laser beam to form an optical tweezer. The fluid used for transporting micro-particles in the experiment is a sample solution. In order to accurately control the flow rate, in the present application, the input connecting pipe 430 and the output connecting pipe 420 are both capillary tubes.

[0076] Thus, in the auxiliary device 1000 for the optical tweezer experiment of the present application, by providing at least two samples and by providing the first switch valve 410 which can be switched, the sample in the same channel 1 of the microfluidic chip 100 can be replaced by switching the first switch valve 410 when needed, greatly improving the efficiency of experiment completion.

[0077] Here, the sample components contained in the at least two sample containers 610 connected by the first switch valve 410 can 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 can be different, or the proportion (i.e. concentration) of at least one component can be different.

[0078] In some embodiments, as shown in Figure 3 and Figure 4 The sample storage 300 includes a storage pool 310 for containing a storage solution, and an adjusting device 320, and the sample container 610 can be placed in the storage pool 310. The adjusting device 320 is connected to the storage pool 310 to adjust the state of the storage solution and the sample. In this way, when the sample appears to be precipitated, etc., the activity of the sample can be improved by starting the adjusting device 320, thereby improving the success rate of the experiment.

[0079] Referring to Figure 4 In some specific embodiments, the adjusting device 320 includes an ultrasonic generator 321 for generating ultrasonic waves to the storage solution to shake the sample. Here, the ultrasonic generator 321 can adopt the structure of the ultrasonic generator known in the prior art, and its structure and principle will not be described here.

[0080] Specifically, the ultrasonic waves can produce high shear force through cavitation to decompose the precipitated molecular groups into smaller particles, so that they are more easily dispersed in the solvent to form a uniform suspension or solution. In this way, the effectiveness of the subsequent optical tweezer experiment is improved.

[0081] In some embodiments, the adjusting device 320 comprises 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 can be understood that the 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, the constant temperature treatment of the sample helps to keep the consistency of the experimental conditions and improve the reliability of the experimental results.

[0082] In some embodiments, referring to Figure 4 , the adjusting device 320 comprises a constant temperature holding device 322, and the constant temperature holding device 322 comprises a refrigeration container 3221, a displacement pump 3224 and a temperature detection member 3225.

[0083] The refrigeration container 3221 is connected with the storage pool 310 through a displacement pipe 3226, and the displacement pump 3224 is arranged on the displacement pipe 3226 to drive the flow of the storage liquid in the displacement pipe 3226 when started, and make the storage liquid in the refrigeration container 3221 and the storage pool 310 flow through the displacement pipe 3226. The temperature detection member 3225 is used to detect the temperature in the storage pool 310, and the detection result of the temperature detection member 3225 is used to control at least the on-off of the displacement pump 3224.

[0084] It can be understood that the temperature in the storage pool 310 is the storage temperature of the sample, so that the sample temperature can be controlled in real time, the automatic holding of the sample temperature is realized, and unnecessary energy consumption is reduced.

[0085] Specifically, the adjusting device 320 further comprises a semiconductor refrigerator 3222, the cold end of the semiconductor refrigerator 3222 is connected with the refrigeration container 3221, and the hot end of the semiconductor refrigerator 3222 is used for heat dissipation. In this way, the heat of the refrigeration container 3221 can be quickly output and dissipated.

[0086] Further, the adjusting device 320 further comprises a heat sink 3223 arranged at the hot end of the semiconductor refrigerator 3222. Thus, the heat dissipation efficiency is improved.

[0087] In some embodiments, as shown in Figure 4 , the sample container 610 is a sample test tube, so that the occupied area is smaller. In particular, the sample test tube can also be selected as a large-capacity test tube.

[0088] Specifically, as shown in Figure 4 , the sample storage device 300 further comprises a sample test tube rack 330, the sample test tube rack 330 is arranged above the storage pool 310, and the sample test tube is placed on the sample test tube rack 330 in a removable manner, so that the neatness and orderliness are improved, and the identification is facilitated.

[0089] In some embodiments, as shown in Figure 3As shown, the auxiliary equipment 1000 for the optical tweezer experiment further comprises a cleaning module 500, which is used for cleaning the sampling tube control assembly 4 or for cleaning the sample container 610. Thus, the sample container 610 can be connected to the sampling tube control assembly 4, and thus the cleaning module 500 can also clean the sample container 610 at the same time.

[0090] It can be understood that, since the input connecting tube 430 and the output connecting tube 420 in the sampling tube control assembly 4 are both capillary tubes, cleaning the capillary tubes in a conventional experiment requires manual processing, is extremely time-consuming, and the cleaning operation is difficult to standardize. In the present application, the cleaning module 500 is used to clean the capillary tubes, which realizes cleaning automation, not only saves the occupation of manual time, but also improves the cleaning standardization.

[0091] Referring to Figure 5 and Figure 6 , 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 is used for connecting the sample container 610 or connecting the input connecting tube 430, and each second input port 512 is used for connecting a cleaning container 620 containing a cleaning reagent. The at least two cleaning containers 620 contain cleaning reagents 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. In this way, different cleaning reagents can be sequentially cleaned.

[0092] When the second output port 511 is connected to the input connecting tube 430, the sampling tube control assembly 4 is opened, and the cleaning reagent flows through the entire sampling tube control assembly 4 and enters the channel 1 to perform 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 tube control assembly 4 is opened, and the cleaning reagent flows through the sample container 610, the entire sampling tube control assembly 4 and enters the channel 1 to perform cleaning.

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

[0095] Specifically, the cleaning module 500 further comprises a distribution box 520, the distribution box 520 is internally provided with a distribution cavity 5201, and is correspondingly provided with a liquid inlet 5202 and a plurality of distribution ports 5203, the liquid inlet 5202 is communicated with the second output port 511, and the plurality of distribution ports 5203 are used for connecting the sample container 610 or the input connecting pipe 430. It can be understood that the sampling control assembly 4 and the cleaning sample container 610 used in the experiment are multiple, the cleaning reagent is divided into multiple paths by using the distribution box 520 to connect the sampling control assembly 4 and the cleaning sample container 610, and the cleaning efficiency can be improved.

[0096] Further, the distribution cavity 5201 is two and is respectively a first distribution cavity 5201-1 and a second distribution cavity 5201-2. The liquid inlet 5202 comprises a first liquid inlet 5202-1 and a second liquid inlet 5202-2, the first liquid inlet 5202-1 is communicated with the first distribution cavity 5201-1, and the second liquid inlet 5202-2 is communicated with the second distribution cavity 5201-2. The plurality of distribution ports 5203 comprise a plurality of first distribution ports 5203-1 and a plurality of second distribution ports 5203-2, the plurality of first distribution ports 5203-1 are communicated with the first distribution cavity 5201-1, the plurality of second distribution ports 5203-2 are communicated with the second distribution cavity 5201-2, the first distribution port 5203-1 is used for connecting the input connecting pipe 430, and the second distribution port 5203-2 is used for connecting the sample container 610.

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

[0098] In this way, the user can select the sampling control assembly 4 and the cleaning sample container 610 according to the needs, and the selection autonomy is improved.

[0099] Specifically, the cleaning module 500 further comprises a first gas pressure control valve 550, an output end of the first gas pressure control valve 550 is connected with the distribution cavity 5201, and an input end of the first gas pressure control valve 550 is used for connecting a driving gas source. In this way, when the cleaning reagent is divided in the distribution box 520, the gas pumps the cleaning reagent to the sampling control assembly 4 or the cleaning sample container 610 by opening the first gas pressure control valve 550. In this way, the flow speed of the cleaning reagent is improved, and the cleaning efficiency is improved.

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

[0101] Specifically, the screw joint buckle 5204 is two clamping plates which are arranged circumferentially and have a gap between the two ends. The sample container 610 has two connecting lugs 611 on the top, and when installed, the two connecting lugs 611 are opposite the two gap positions, and are inserted upward to make the top opening of the sample container 610 connected with the second dispensing port 5203-2. Then the sample container 610 is rotated so that the two connecting lugs 611 are clamped above the two clamping plates.

[0102] Further, the cleaning module 500 further comprises a plug 5205 for plugging the first dispensing port 5203-1 and the second dispensing port 5203-2, so that the unused first dispensing port 5203-1 and the second dispensing port 5203-2 can be plugged.

[0103] In some embodiments, as shown, Figure 5 As shown, the cleaning module 500 further comprises a fixing seat 560 and a support frame 570, and the second switching valve 510 is installed on the fixing seat 560. The support frame 570 is installed on the fixing seat 560, and the dispensing box 520 is rotatably installed on the support frame 570, so as to adjust the position of the dispensing port 5203.

[0104] The fixing seat 560 is a basic support structure which can be in the form of a box to facilitate the accommodation of various components.

[0105] The dispensing box 520 is rotatably installed on the support frame 570, so that the orientation of the dispensing port 5203 can be adjusted. When the sampling tube control assembly 4 and the cleaning sample container 610 are installed and removed, the dispensing port 5203 can be placed outwardly or horizontally. When the sampling tube control assembly 4 and the cleaning sample container 610 are installed, the dispensing port 5203 can be set downwardly.

[0106] Specifically, the fixing seat 560 is a box body with one horizontal side open, facilitating manual installation of the sampling tube control assembly 4 and the cleaning sample container 610 on the dispensing box 520.

[0107] Specifically, the support frame 570 is a frame body, and the dispensing 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] Further, one side of the fixing seat 560 forms a through opening 561, and the cleaning container 620 is used to be placed outside the fixing seat 560 and 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 the optical tweezer experiment, the at least one sampling control assembly 4 is connected to the plurality of sample containers 610 through the first switching valve 410. Here, the samples in the plurality of 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. The plurality of sample containers 610 connected to the same first switching valve 410 can also have different sample compositions, for example, at least one component of the sample can be different, or the proportion (i.e., concentration) of at least one component can be different.

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

[0111] The plurality of sampling control assemblies 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 two channels 1 to approach and then move away from each other, the experimental phenomenon and the measurement result are obtained.

[0113] When the number of measurement results obtained reaches a set number, or when the experimental phenomenon does not meet the first set condition, or when the measurement result exceeds the first set range, the 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 amount of the sample flowing into the corresponding channel 1.

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

[0115] Here, the first set condition can be set according to the specific experiment, for example, in the optical tweezer experiment, when the laser beam is projected onto a certain 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 set range can be set according to the specific experiment, for example, in the optical tweezer experiment, the measurement result is the pulling force value, and the first set range is that the measurement result is within a predetermined pulling force value range.

[0117] According to the experimental method of the auxiliary device 1000 for the optical tweezer experiment according to the third aspect of the present application, the experimental steps are as follows:

[0118] The plurality of sampling control assemblies 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;

[0119] When the first laser beam and the second laser beam emitted by the laser device 200 pull the two channels 1 of the single molecule phase close to each other and then far away from each other, the experimental phenomenon and the measurement result are obtained;

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

[0121] That is, if the state of the sample is not ideal in the experiment, the control adjustment device 320 can be automatically started.

[0122] Here, the second set condition can be set according to specific experiments, for example, in the optical tweezer 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 set range can be set according to specific experiments, for example, the measurement result of the optical tweezer experiment is the pulling force value, and the second set range is that the measurement result is within a predetermined pulling force value range.

[0124] The cleaning method of the auxiliary device 1000 for the optical tweezer experiment according to the fourth aspect of the present application comprises the following steps:

[0125] After the first switching valve 410 communicates the first output port 411 with one of the first input ports 412, the second switching valve 510 is communicated with one of the second input ports 512, and the cleaning reagent in the corresponding cleaning container 620 is driven to enter the separation box 520 through the second switching valve 510, and then the cleaning reagent is driven to enter the sampling tube control assembly 4 or the sample container 610.

[0126] Then switch at least one of the first switching valve 410 and the second switching valve 510, so that the first output port 411 is communicated with another first input port 412, and / or the second output port 511 is communicated with another second input port 512.

[0127] In this way, the cycle is repeated until each capillary completes at least one cleaning cycle.

[0128] In one cleaning cycle, the capillary sequentially flows through all kinds of cleaning reagents in time sequence.

[0129] In this way, the cleaning efficiency can be improved, the manual input time can be reduced, and the standardization and normalization of cleaning can be improved.

[0130] In one specific embodiment, as shown in Figure 5 The cleaning container 620 is three, respectively containing acid solution, alkaline solution and pure water.

[0131] Each capillary needs to complete at least one cleaning cycle, i.e. the second switch valve 510 is switched to connect the second input port 512 connected with the acidic liquid to the second output port 511, then switched to connect the second input port 512 connected with the alkaline liquid to the second output port 511, and then switched to connect the second input port 512 connected with the clean water to the second output port 511, so that the capillary is cleaned by the acidic liquid, the alkaline liquid and the clean water in sequence. Alternatively, in one cleaning cycle, the second switch valve 510 is switched to connect the second input port 512 connected with the alkaline liquid to the second output port 511, then switched to connect the second input port 512 connected with the acidic liquid to the second output port 511, and then switched to connect the second input port 512 connected with the clean water to the second output port 511, so that the capillary is cleaned by the alkaline liquid, the acidic liquid and the clean water in sequence.

[0132] It can be understood that the same cleaning agent can be used for multiple times in the cleaning of the same capillary. For example, a capillary needs to be cleaned by the acidic liquid, the alkaline liquid and the clean water in sequence. In this case, there can be multiple cleaning sequences, such as 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 the present specification, the description referring to the terms "embodiment", "example", etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description 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 application have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and alterations can be made thereto without departing from the principles and the spirit of the present application, and the scope of the present application is defined by the claims and their equivalents.

Claims

1. An auxiliary device for optical tweezers experiments, wherein the optical tweezers experiments are performed using a microfluidic chip (100) and a laser device (200) to conduct single-molecule experiments, wherein the microfluidic chip (100) is provided with at least two channels (1), each channel (1) having a flow inlet (101), characterized in that, The auxiliary equipment (1000) for the optical tweezer experiment comprises: a sample storage (300) for placing a plurality of sample containers (610), each of the sample containers (610) being used for storing a sample; a sample feeding module (400), the sample feeding module (400) comprising at least two sample tube control assemblies (4), the sample tube control assemblies (4) being arranged in one-to-one correspondence with the channels (1), one end of each of the sample tube control assemblies (4) being used for connecting at least one of the sample containers (610), the other end of each of the sample tube control assemblies (4) being used for connecting the flow passage inlet (101) of the channel (1), and one end of each of the sample tube control assemblies (4) connected with the channel (1) being provided with a sample control valve (440); wherein at least one of the sample tube control assemblies (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 with the sample control valve (440) through an output connecting pipe (420), each of the first input ports (412) being connected with one of the sample containers (610) through an input connecting pipe (430), and the first switching valve (410) being switchably controlled to communicate one of the first input ports (412) with the first output port (411); wherein the input connecting pipe (430) and the output connecting pipe (420) are capillary tubes; the auxiliary equipment (1000) for the optical tweezer experiment further comprises a cleaning module (500) for cleaning the sample tube control assemblies (4) and / or the sample containers (610), the cleaning module (500) comprising a second switching valve (510); the second switching valve (510) comprising a second output port (511) and at least two second input ports (512), the second output port (511) being used for connecting the sample containers (610) or the input connecting pipe (430), and each of the second input ports (512) being used for connecting a cleaning container (620) containing a cleaning reagent, at least two of the cleaning containers (620) containing cleaning reagents of different types; the second switching valve (510) being switchably controlled to communicate one of the second input ports (512) with the second output port (511).

2. The auxiliary device for optical tweezer experiments according to claim 1, characterized in that, the sample storage (300) comprises: a storage pool (310) for containing a storage solution, the sample containers (610) being placed in the storage pool (310); an adjusting device (320) connected with the storage pool (310) to adjust the state of the storage solution and the sample; the adjusting device (320) comprising at least one of an ultrasonic generator (321) and a constant temperature maintaining device (322), the ultrasonic generator (321) being used for generating ultrasonic waves to the storage solution to shake the sample, and the constant temperature maintaining device (322) being used for maintaining the storage solution and the sample at a set temperature.

3. The auxiliary device for optical tweezer experiments according to claim 2, characterized in that, The adjusting device (320) comprises a constant-temperature holding device (322), which comprises: a refrigeration container (3221) connected with the storage pool (310) through a displacement pipe (3226); a displacement pump (3224) arranged on the displacement pipe (3226) to drive the liquid flow in the displacement pipe (3226) when started and make the liquid in the refrigeration container (3221) and the storage pool (310) flow through the displacement pipe (3226); a temperature detecting member (3225) for detecting the temperature in the storage pool (310), and the detection result of the temperature detecting member (3225) is used to control at least the on-off of the displacement pump (3224).

4. The auxiliary device for optical tweezer experiments of claim 1, wherein, The cleaning module (500) further comprises: a liquid distribution box (520) provided with a liquid distribution cavity (5201) therein, and provided with a liquid inlet (5202) and a plurality of liquid outlets (5203) correspondingly, the liquid inlet (5202) is communicated with the second output port (511), and the plurality of liquid outlets (5203) are used for connecting the sample container (610) or the input connecting pipe (430).

5. The auxiliary device for optical tweezer experiments according to claim 4, characterized in that, The liquid distribution cavity (5201) is two and is a first liquid distribution cavity (5201-1) and a second liquid distribution cavity (5201-2) respectively; The liquid inlet (5202) comprises a first liquid inlet (5202-1) and a second liquid inlet (5202-2), the first liquid inlet (5202-1) is communicated with the first liquid distribution cavity (5201-1), and the second liquid inlet (5202-2) is communicated with the second liquid distribution cavity (5201-2); The plurality of liquid outlets (5203) comprise a plurality of first liquid outlets (5203-1) and a plurality of second liquid outlets (5203-2), the plurality of first liquid outlets (5203-1) are communicated with the first liquid distribution cavity (5201-1), the plurality of second liquid outlets (5203-2) are communicated with the second liquid distribution cavity (5201-2), the first liquid outlet (5203-1) is used for connecting the input connecting pipe (430), and the second liquid outlet (5203-2) is used for connecting the sample container (610); The cleaning module (500) further comprises a third switch valve (540); The third switch valve (540) comprises a third input port (542) and two third output ports (541), the third input port (542) is connected with the second output port (511), and the two third output ports (541) are connected with the first liquid inlet (5202-1) and the second liquid inlet (5202-2) respectively, and the third switch valve (540) can be switched to control the third input port (542) to be communicated with one of the third output ports (541).

6. The auxiliary device for optical tweezer experiments according to claim 4, characterized in that, The cleaning module (500) further comprises a first air pressure control valve (550), an output end of the first air pressure control valve (550) being connected to the distribution cavity (5201), and an input end of the first air pressure control valve (550) being used for connecting a driving air source.

7. An experimental method using the auxiliary device for optical tweezer experiments according to any one of claims 1 to 6, characterized in that, At least one of the sampling control assemblies (4) is connected to a plurality of sample containers (610) through the first switch valve (410). The experimental steps are: A plurality of the sampling control assemblies (4) are opened, and a plurality of samples flow into a plurality of channels (1) correspondingly, wherein the first switch valve (410) is in communication with one of the first input ports (412) and the first output port (411). 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) to approach and then move away from each other, experimental phenomena and measurement results are obtained. When the number of the measurement results reaches a set number of times, or when the experimental phenomena do not meet a first set condition, or when the measurement results exceed a first set range, the first switch valve (410) is controlled to be in communication with another first input port (412) and the first output port (411), so as to adjust the composition, concentration or dosage of the sample flowing into the corresponding channel (1).

8. An experimental method using the auxiliary device for optical tweezer experiments according to claim 2, characterized in that, The experimental steps are: A plurality of the sampling control assemblies (4) are opened, and a plurality of samples flow into a plurality of channels (1) correspondingly, wherein the first switch valve (410) is in communication with one of the first input ports (412) and the first output port (411). 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) to approach and then move away from each other, experimental phenomena and measurement results are obtained. When the experimental phenomena do not meet a second set condition, or when the measurement results exceed a second set range, the adjustment device (320) is started to adjust the state of the sample.

9. A cleaning method using the auxiliary device for optical tweezer experiments according to any one of claims 1 to 6, characterized in that, The cleaning steps include: After the first switch valve (410) is in communication with one of the first input ports (412) and the first output port (411), the second switch valve (510) is in communication with one of the second input ports (512) and the second output port (511), the cleaning reagent in the corresponding cleaning container (620) is driven to enter the distribution box (520) through the second switch valve (510), and then the cleaning reagent is driven to enter the sampling control assembly (4) or the sample container (610). Then, at least one of the first switch valve (410) and the second switch valve (510) is switched, so that the first output port (411) is in communication with another first input port (412), and / or the second output port (511) is in communication with another second input port (512). The cycle is repeated until each of the capillaries completes at least one cleaning cycle. In one cleaning cycle, the capillaries flow through all kinds of cleaning reagents in chronological order.

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