Liquid transfer device and method, biochemical substance reaction device, and biochemical substance analysis device and method

Through the cooperation of the liquid transfer device and the reaction platform, the rapid and uniform replacement and reaction of liquids during gene sequencing are achieved, and the problems of high costs, low throughput and waste of reagents in the prior art are solved, and the sequencing efficiency and device performance are improved.

CN114556110BActive Publication Date: 2025-07-08MGI TECH CO LTD
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Patent Information

Application Number
CN201980101459.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2019-12-26
Publication Date
2025-07-08
Estimated Expiration
2039-12-26

AI Technical Summary

Technical Problem

The existing gene sequencing technology has problems such as high cost, low throughput, serious waste of reagents, cross-contamination of reagents and chip damage, especially the flow cell technology and robotic arm dipping methods in precise temperature control and fluid control.

Method used

The liquid transfer device is used to cooperate with the reaction platform to achieve liquid transfer through the relative movement between the substrate and the sample carrier. A variety of liquids are evenly arranged on the substrate by using the liquid distribution device, combining temperature control and adsorption devices to prevent the substrate from bending, and achieving rapid and uniform liquid replacement and reaction.

Benefits of technology

It improves liquid utilization, reduces reagent consumption, avoids chip damage, improves sequencing throughput and device performance, and reduces costs.

✦ Generated by Eureka AI based on patent content.

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Abstract

A liquid transfer device (1, 2, 5, 6, 7, 81) for liquid transfer between a sample carrier (32) of a reaction platform (3), comprising a substrate (11, 21, 51, 61, 71), a driving device (14, 54, 64, 74) and a control device (17, 57, 67, 77), the control device (17, 57, 67, 77) being configured to control the driving device (14, 54, 64, 74) to drive the substrate (11, 21, 51, 61, 71) to move towards the reaction platform (3), so that the moving substrate (11, 21, 51, 61, 71) passes by the sample carrier (32) and liquid transfer is performed between the substrate (11, 21, 51, 61, 71) and the sample carrier (32), the liquid transfer being to transfer the liquid carried by the substrate (11, 21, 51, 61, 71) to the sample carrier (32) and / or to transfer the liquid on the sample carrier (32) to the substrate (11, 21, 51, 61, 71). In addition, a related liquid transfer method, a biochemical substance reaction device (8), and a biochemical substance analysis device (9a, 9b) and method are provided, which improve the throughput of biochemical reactions and analysis and reduce costs.
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Description

Technical Field

[0001] The present invention relates to the field of biochemical reactions, and particularly to a liquid transfer device and method used in biochemical reactions, a biochemical substance reaction device, and a biochemical substance analysis device and method. Background Art

[0002] Existing second-generation gene sequencing methods require precise temperature control and fluid control, which are costly and prone to uneven reaction phenomena. The chemical reagents used in gene sequencing reactions are all disposable, with low utilization rates, increasing the sequencing cost, and there is also a low throughput situation. For example, in the currently widely used flow cell technology, multiple rounds of photographing are carried out using a flow cell composed of two flat media with biological information attached up and down to achieve the recognition of the base sequence. However, the flow cell technology limits the fluid velocity because when the flow rate is too fast, based on Bernoulli's principle, the upper plate of the flow cell will be subjected to a downward pressure and break, and be adsorbed onto the chip, thus damaging the biological information on the chip. At the same time, the flow cell technology increases the cost. The sequencing process requires up to 200 "reaction - photographing" cycles of various reagents, and the liquid thickness on the chip surface during each cycle is the gap between the two flat media, but the too small gap is difficult to assemble. Moreover, the flow cell technology causes waste of reagents and time. Each cycle requires a complete replacement of the previous reagent. The existing small gap makes the surface force dominant, and more of the next reagent is needed for flushing before the reaction can start. Therefore, the above three points limit the performance, time, and cost of sequencing.

[0003] To reduce costs and increase throughput, the prior art also provides a method of using a robotic arm to grab a bare chip, dip the reagent in different reagent tanks, and use the dipped thin-layer reagent for reaction to reduce the consumption of reagents and replace reagents. The method of dipping reagents improves the throughput to a certain extent and reduces the reagent cost. However, there are problems such as reagent cross-contamination affecting the sequencing quality, uneven liquid thickness resulting in the chip drying out, and unfavorable factors such as the system being too complex. Summary of the Invention

[0004] In order to solve at least one of the above problems of the prior art and / or other potential problems, it is necessary to propose a portable sample addition device.

[0005] In a first aspect, a liquid transfer device is provided. The liquid transfer device is used for liquid transfer between a sample carrier of a reaction platform, and includes a substrate, a driving device, and a control device. The control device is used to control the driving device to drive the substrate to move towards the reaction platform, so that the moving substrate passes through the sample carrier and performs liquid transfer with the sample carrier. The liquid transfer is to transfer the liquid carried by the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate.

[0006] Further, the liquid transfer device further includes a liquid distribution device, which is used to distribute liquid onto the substrate, or the liquid distribution device is used to distribute multiple liquids onto the substrate according to a preset time sequence.

[0007] Further, the liquid distribution device includes a liquid outlet mechanism, a fluid power module, a valve device and a liquid storage device. The fluid power module and the valve device are used to receive the control of the control device to control the liquid to flow out of the liquid storage device and then be distributed onto the substrate through the liquid outlet mechanism.

[0008] Further, the liquid outlet mechanism is a die head, and the die head distributes the liquid onto the substrate by means of coating.

[0009] Further, the liquid distribution device is a printing device, and the printing device distributes the liquid onto the substrate by means of printing; or the liquid distribution device is an anilox roll or a screen printing device.

[0010] Further, the thickness of the liquid distributed by the liquid distribution device onto the substrate is less than 200 microns.

[0011] Further, when the liquid distribution device distributes multiple liquids onto the substrate, the multiple liquids are connected in sequence on the substrate; or the multiple liquids include reaction reagents and buffer reagents, and the buffer reagents connect the reaction reagents located in front and behind; or the head and tail ends of the buffer reagents are respectively stacked with the end parts of the reaction reagents located in front and behind.

[0012] Further, the liquid distribution device includes a liquid storage device, and the liquid storage device is a temperature-controlled memory.

[0013] Further, the substrate is a coil, or the substrate is a transparent material, or the hydrophilicity, hydrophobicity, lipophilicity and lipophobicity of the substrate are adapted to the properties of the liquid.

[0014] Further, the distance between the substrate and the sample carrier is greater than zero but less than the sum of the thickness of the liquid on the substrate and the thickness of the liquid on the reaction platform.

[0015] Further, the liquid transfer device further includes an adsorption device, which is located on the side of the substrate away from the reaction platform, and the adsorption device is used to adsorb the substrate to prevent the substrate from bending and contacting the sample carrier.

[0016] Further, the adsorption device is a planar object coated with a liquid layer. The surface of the planar object that contacts the substrate is coated with the liquid layer and is parallel to the moving direction of the substrate. The planar object adsorbs the substrate through the liquid layer; alternatively, the adsorption is a vacuum adsorption device, and the surface of the vacuum adsorption device that contacts the substrate is parallel to the moving direction of the substrate.

[0017] Further, the liquid transfer device further includes a pressing device disposed on a side of the substrate away from the reaction platform. The pressing device is used to press the substrate to form a sealing effect between the substrate and the reaction platform to prevent liquid evaporation.

[0018] Further, the control device is further used to determine whether to activate the pressing device to press the substrate according to the temperature required by the liquid participating in the reaction on the sample carrier.

[0019] Further, the liquid transfer device further includes a liquid cleaning device disposed at the rear end of the moving path of the substrate. The liquid cleaning device is used to clean the liquid remaining on the substrate after the substrate passes through the sample carrier.

[0020] Further, the liquid cleaning device is a dryer and / or a scraper.

[0021] Further, the liquid transfer device further includes a leveling device disposed at the front end of the moving path of the substrate. The leveling device is used to level the liquid after the liquid is arranged on the substrate and before it is transferred to the sample carrier.

[0022] Further, the leveling device is a scraper.

[0023] Further, the liquid transfer device further includes an accelerating device, and the accelerating device is used to accelerate the liquid transfer between the substrate and the sample carrier.

[0024] Further, the accelerating device is a sound wave, a laser, and / or a magnetic acceleration device.

[0025] Further, there are a plurality of substrates, and the plurality of substrates share the liquid distribution device. The liquid distribution device includes a liquid outlet mechanism, and the liquid outlet mechanism is controlled by the control device to move along a guide rail to distribute liquid to the plurality of substrates.

[0026] In a second aspect, a biochemical substance reaction device is provided. The biochemical substance reaction device includes the above-mentioned liquid transfer device and a reaction platform, and the reaction platform includes a sample carrier for loading samples.

[0027] Further, the reaction platform is a movable platform that can move away from and close to the substrate, and the control device is further configured to determine whether to start moving the reaction platform according to the temperature required for the liquid participating in the reaction on the sample carrier.

[0028] Further, a spacer facing the substrate is provided on the reaction platform, and the spacer spaces the distance between the substrate and the reaction platform.

[0029] Further, the reaction platform further includes a carrier stage, and the spacer is provided on the carrier stage, or the spacer is provided on the sample carrier.

[0030] Further, the spacer is provided on the reaction platform by means of gluing or photoresist.

[0031] Further, a temperature control device is provided on the reaction platform, and the control device is further configured to control the temperature control device to heat or cool according to the temperature required for the liquid in which the reaction occurs.

[0032] Further, an acceleration device is further provided on the reaction platform, and the acceleration device is used to accelerate the liquid transfer between the substrate and the reaction platform.

[0033] Further, the acceleration device is a sonic wave, laser, and / or magnetic acceleration device.

[0034] In a third aspect, a biochemical substance analysis device is provided, and the biochemical substance analysis device includes the above-mentioned biochemical substance reaction device and detection device.

[0035] Further, the detection device performs detection on the sample on the sample carrier through the substrate.

[0036] Further, the biochemical substance analysis device further includes a transfer device, and the transfer device is used to transfer the sample carrier between the biochemical substance analysis device and the detection device.

[0037] In a fourth aspect, a liquid transfer method is provided, and the method includes:

[0038] Controlling the substrate to move in the direction where the reaction platform is located, where the reaction platform includes a sample carrier carrying a sample; and

[0039] Controlling the substrate to pass through the reaction platform and perform liquid transfer between the substrate and the sample carrier, and the liquid transfer is to transfer the liquid on the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate.

[0040] Further, the method further includes: disposing a liquid on the substrate; or, disposing a liquid on the moving substrate, where the liquid is used for the above liquid transfer between the substrate and the sample carrier.

[0041] Further, the manner of disposing the liquid is coating, printing or spraying.

[0042] Further, disposing a liquid on the substrate is: disposing a plurality of liquids on the substrate according to a preset time sequence.

[0043] Further, the plurality of liquids are connected end to end.

[0044] Further, the plurality of liquids include a buffer reagent and two or more reaction reagents, and the two reaction reagents distributed front and back on the substrate are connected by the buffer reagent; or, the two ends of the buffer reagent are respectively stacked with the ends of the reaction reagents located front and back.

[0045] Further, the thickness of the liquid disposed on the substrate is less than 200 microns.

[0046] Further, the method further includes: disposing a liquid on the sample carrier, where the liquid is used for the above liquid transfer between the substrate and the sample carrier.

[0047] Further, the manner of disposing the liquid is coating or spraying.

[0048] Fifthly, a biochemical substance analysis method is provided, and the biochemical substance analysis method includes:

[0049] The liquid transfer method as described above; and

[0050] After waiting for the sample on the sample carrier to react completely with the liquid, performing detection on the sample.

[0051] Further, the method further includes: transferring the sample carrier to a detection device so that the detection device performs the detection.

[0052] The liquid transfer device and method, biochemical substance reaction device, and biochemical substance analysis device and method provided by the embodiments of the present invention are as follows. Under the control of the control device, the substrate is driven by the driving device to move in one direction. When the substrate passes through the liquid distribution device, the liquid distribution device uniformly covers one or more liquids on the substrate with a certain length and thickness. When the substrate passes parallel above the reaction platform at a certain speed or speed combination and at a certain height, the liquid covered on it contacts the sample carrier. The substrate continues to move, and fresh liquid or other types of liquid continue to contact the sample carrier to replace the original liquid, enabling the reaction to continue or other reactions to occur. After the predetermined reaction is completed, the sample carrier is detected in situ, or the sample carrier is transferred to the detection device for detection. Replacing the liquid for the sample carrier with a moving substrate can achieve the coating of extremely thin liquids (such as reagents), greatly saving liquid and improving the utilization rate of the liquid. In addition, the replacement of the liquid is made more rapid, and since the substrate can be in the form of a roll and does not require installation, the throughput of biological property determination is greatly improved. Furthermore, by negatively adsorbing the substrate and / or using spacers to space the substrate and the sample carrier, damage to the sample carrier and the sample is avoided, and since the substrate is not brittle glass, the speed of fluid arrangement on the substrate is increased, and the problem of cracking of the upper plate of the flow cell does not occur, thus avoiding damage to the sample. At the same time, by adjusting the timing, multiple sample carriers can share the liquid transfer device, and the detection and reaction times of different sample carriers can overlap, thereby further saving time and cost and improving the overall performance of the device. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments of the present invention will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other drawings based on these drawings without creative efforts.

[0054] Figure 1 It is a schematic diagram of the principle of the liquid transfer device in the embodiments of the present invention.

[0055] Figure 2 It is a case of arranging liquid on the substrate according to the time sequence as an example.

[0056] Figure 3 It is a schematic structural diagram of the liquid transfer device provided by Embodiment 1 of the present invention.

[0057] Figure 4 It is a schematic diagram of die coating liquid onto the substrate.

[0058] Figure 5 It is a positional relationship diagram of the liquid transfer device, the sample carrier, and the detection device in one way.

[0059] Figure 6 It is a diagram showing the positional relationship among the liquid transfer device, the sample carrier, and the detection device in another way.

[0060] Figure 7 and Figure 8 It is a schematic diagram of the distance between the substrate and the sample carrier.

[0061] Figure 9 It is a schematic diagram of arranging a spacer on the sample carrier.

[0062] Figure 10 It is a schematic diagram of arranging a spacer on the stage.

[0063] Figure 11 and Figure 12 It is a schematic diagram of arranging an adsorption device to adsorb the substrate.

[0064] Figure 13 It is a schematic diagram of arranging a temperature control device on the stage.

[0065] Figure 14 It is a schematic diagram of arranging a pressing device on the side of the substrate away from the reaction platform.

[0066] Figure 15 and Figure 16 It is a schematic diagram of arranging a liquid cleaning device at the rear end in the moving direction of the substrate to clean the liquid on the substrate.

[0067] Figure 17 It is a schematic diagram of arranging a flattening device at the front end in the moving direction of the substrate to flatten the liquid on the substrate.

[0068] Figure 18 It is a schematic diagram of some components of the liquid transfer device provided in the second embodiment.

[0069] Figure 19 It is a schematic diagram of some components of the liquid transfer device provided in the third embodiment.

[0070] Figure 20 It is a schematic diagram of some components of the liquid transfer device provided in the fourth embodiment.

[0071] Figure 21 is Figure 20 a schematic diagram of the composition of the printing device in the liquid transfer device shown.

[0072] Figure 22 It is a schematic diagram of some components of the liquid transfer device provided in the fifth embodiment.

[0073] Figure 23 It is a schematic diagram of the biochemical substance reaction device provided in the sixth embodiment.

[0074] Figure 24Schematic diagram of the biochemical substance analysis device provided for Example 7.

[0075] Figure 25 Schematic diagram of the biochemical substance analysis device provided for Example 8.

[0076] Figure 26 Flow schematic diagram of the liquid transfer method provided for Example 9.

[0077] Figure 27 Flow schematic diagram of the biochemical substance analysis method provided for Example 10.

[0078] The following specific implementation manners will further illustrate the present invention in conjunction with the above drawings.

[0079] Description of main component symbols

[0080] Liquid transfer devices 1, 2, 5, 6, 7, 81; Reaction platform 3

[0081] Detection device 41; Transfer device 43

[0082] Biochemical substance reaction 8; Biochemical substance analysis 9a, 9b

[0083] Device

[0084] Substrates 11, 21, 51, 61, 71; Liquid distribution devices 13, 63, 73

[0085] Drive devices 14, 54, 64, 74; Tensioning device 15

[0086] Guide devices 16, 66; Control devices 17, 57, 67, 6312, 77

[0087] Rewinding device 141; Unwinding device 143

[0088] Dies 131, 231; Liquid storage device 132

[0089] Reagent section 111; Gap 1311

[0090] Liquid L1; Overlap area 1111

[0091] Carrier table 31; Sample carrier 32

[0092] Liquid layers H1, H2, 181; Spacers 321, 311

[0093] Object plane 180; Vacuum adsorption device 182

[0094] Temperature control device 33; Pushing device 183

[0095] Dryer 184, scraper 185

[0096] Waste bin 186, leveling device 187

[0097] Guide rails 232, 661, printing device 631

[0098] Storage device 6311, printing device 6313

[0099] Anilox roll 731, prefabricated pattern 7311

[0100] Steps S2601, S2602, residual liquid H3 S2701 - S2703 Detailed implementation manners

[0101] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts shall fall within the protection scope of the present invention.

[0102] It should be noted that when a component is referred to as being "fixed to" or "installed on" another component, it can be directly on the other component or there may also be an intermediate component. When a component is considered to be "arranged on" another component, it can be directly arranged on the other component or there may be an intermediate component at the same time. The term "and / or" as used herein includes all and any combinations of one or more of the related listed items.

[0103] Please refer to Figure 1 As shown, it is a schematic principle diagram of the liquid transfer method implemented by the liquid transfer device of the present invention. The liquid transfer device 1 includes a substrate 11, and the substrate 11 is controlled to pass above the reaction platform 3 at a certain speed, loading new liquid onto the reaction platform 3 and / or taking away the original liquid on the reaction platform 3. Further, the substrate 11 can be a substrate without carrying liquid or a substrate carrying liquid. By using the substrate 11 without carrying liquid or the area of the substrate 11 without carrying liquid passing above the reaction platform 3, by controlling the relative speed between the substrate 11 and the reaction platform 3, the original liquid on the reaction platform 3 can be wiped off, and by using the substrate 11 carrying liquid or the area of the substrate 11 carrying liquid passing above the reaction platform 3, by controlling the relative speed between the substrate 11 and the reaction platform 3, it is possible to: 1. Wipe off the original liquid (if any) on the reaction platform 3; 2. Load new liquid onto the reaction platform 3 so that the next round of reaction can start on the reaction platform 3.

[0104] By controlling the relative movement of two opposite planes (such as the substrate 11 and the reaction platform 3), the moving plane (such as the substrate 11) imparts a certain velocity to the liquid sandwiched between the two planes. This velocity is related to the interaction force between the moving plane (such as the substrate 11) and the liquid, the interaction force between the fixed plane (such as the reaction platform 3) and the liquid, the thickness of the liquid layer, and the liquid viscosity. For relevant theories, please refer to the research on "Couette flow" in the prior art. Therefore, after the substrate 11 is controlled to move on the reaction platform 3 for a certain time or a certain length of distance, the liquid on the reaction platform 3 will be carried away by the substrate 11 or replaced by the liquid carried by the substrate 11.

[0105] The liquid transfer device 1 may further include a liquid distribution device 13, which distributes the liquid L1 on the substrate 11 by means such as coating or spraying. When multiple liquids L1 need to be distributed, the liquid distribution device 13 can adopt multiple liquid outlet mechanisms, and the multiple liquid outlet mechanisms are controlled to output different liquids L1 in a preset time sequence. Each liquid L1 is controlled to be distributed on the substrate 11 for a certain length according to requirements (such as according to the reaction time with the sample on the reaction platform 3). When multiple liquids L1 need to be distributed, the liquid distribution device 13 can also adopt one liquid outlet mechanism, and the liquid outlet mechanism is controlled to output different liquids L1 in a preset time sequence. Each liquid L1 is controlled to be distributed on the substrate 11 for a certain length according to requirements.

[0106] Please refer to Figure 2 as shown in Figure 2 an example of distributing multiple liquids on the substrate 11 in time sequence is given. In this example, the multiple liquids include reaction reagents A, B, C, D and buffer reagent E. In one cycle, they are distributed on the substrate 11 in the order of reaction reagent A, buffer reagent E, reaction reagent B, buffer reagent E, reaction reagent C, buffer reagent E, reaction reagent D and buffer reagent E. The buffer reagent E is used to clean the previous reaction reagent. There is partial overlap between the buffer reagent E and the adjacent reaction reagents before and after, that is, the head of each section of the buffer reagent E overlaps to the tail of the previous reaction reagent, and the head of the next reaction reagent overlaps to the tail of the buffer reagent E, so that the reagents with different surface tensions on the substrate 11 can be connected, reducing the influence of surface tension when the substrate 11 brings different liquids to the reaction platform 3 and avoiding the introduction of bubbles. After the reaction reagents A, B, C, D and buffer reagent E are distributed on the substrate 11 in a preset time sequence, a reagent segment 111 for one reaction cycle is formed on the substrate 11. Among them, the area indicated by the label 1111 in the reagent segment 111 is the overlapping area of the buffer reagent E and the reaction reagent.

[0107] Example 1

[0108] Please refer to Figure 3As shown, it is a schematic structural diagram of the liquid transfer device 1 in Embodiment 1. Except for the substrate 11 and the liquid distribution device 13, the liquid transfer device 1 further includes a driving device 14, a tensioning device 15, a guiding device 16, and a control device 17. The driving device 14 is used to drive the substrate 11 to move at a certain speed. In this embodiment, the driving device 14 includes a winding device 141 and an unwinding device 143 that are spaced apart. Both ends of the substrate 11 are respectively wound around the winding device 141 and the unwinding device 143, and the substrate 11 is pulled to move at a certain speed by the rotation of the winding device 141. The tensioning device 15 is arranged on the moving path of the substrate 11 and is used to tension the substrate 11 to facilitate the liquid to be arranged on the substrate 11 and improve the uniformity of liquid arrangement. The guiding device 16 is used to guide the substrate 11 to move along a preset path. When the preset moving path of the substrate 11 is the straight-line distance between the unwinding device 143 and the winding device 141, the guiding device 16 can be omitted. In this embodiment, the guiding device 16 is a guiding wheel. In this embodiment, the liquid outlet mechanism of the liquid distribution device 13 adopts a die head. According to the types of liquids to be arranged, the liquid distribution device 13 includes a plurality of die heads 131. The plurality of die heads 131 are distributed along the moving path of the substrate 11, and each die head 131 is connected to a liquid storage device 132 for storing a specific liquid and is controlled to output a certain amount of liquid. In this embodiment, the liquid distribution device 13 includes five die heads 131 and five liquid storage devices 132. The five liquid storage devices 132 are respectively used to store four reaction reagents A, B, C, D and one buffer reagent E. The five die heads 131 are respectively used to output the five reagents A - E. The timing of the die heads 131 outputting reagents can refer to Figure 2 As shown, finally, a plurality of reagent segments 111 are formed on the substrate 11. Each reagent segment 111 passes through the reaction platform 3, representing that a round of reaction with the sample on the reaction platform 3 is completed. For example, in gene sequencing, each reagent segment 111 passing through the reaction platform 3 represents that a determination reaction of a DNA node for adenine, guanine, thymine, and cytosine with the sample on the reaction platform 3 is completed.

[0109] Please refer to Figure 4As shown, it is a schematic diagram of the die head 131 coating a liquid onto the substrate 11. The die head 131 has a liquid outlet slit 1311, and the slit 1311 faces the substrate 11. The liquid distribution device 13 further includes a valve device 133. The valve device 133 can be an electromagnetic valve or other types of devices that control the flow and disconnection of fluids. The valve device 133 controls the liquid flowing to the die head 131 under the control of the control device 17. According to the preset timing, when it is required to coat a liquid from the die head 131 onto the substrate 11, the control device 17 opens the valve device 133 associated with the die head 131. The liquid flows out from the corresponding liquid storage device 132 to the die head 131, and then flows out from the slit 1311 of the die head 131. With the movement of the substrate 11 and the continuous supply of the liquid in the die head 131, the liquid is evenly spread on the substrate 11 by overcoming the intermolecular force of the liquid. Further, the liquid distribution device 13 may also include a fluid power module (not shown in the figure). The fluid power module can be a power device such as a pump that provides power for the liquid to enter the die head 131 and be coated from the die head 131 onto the substrate 11. The power provided by the fluid power module can help overcome the intermolecular force when the liquid forms a thin layer on the substrate 11, so that the liquid is evenly spread on the substrate 11 without defects or with few defects (such as pinhole defects).

[0110] It can be understood that by using the control device 17 to control each valve device 133 and the fluid power module of the liquid distribution device 13, the length, thickness of different liquids laid and the spacing between different liquids can be adjusted as needed. Preferably, to avoid introducing air bubbles and avoid large changes in the surface tension of the liquid on the reaction platform 3, which may damage the sample information on the reaction platform 3, a 0-spacing can be set between different liquids, or, as Figure 2 shown, when using a buffer reagent to connect different reaction reagents, the head and tail ends of the buffer reagent overlap with the front and back reaction reagents.

[0111] In this embodiment, the material of the substrate 11 includes corona-treated polyethylene terephthalate film (abbreviated as PET film), polystyrene film (abbreviated as PS film), polyethylene film (abbreviated as PE film) or other materials with hydrophilic and hydrophobic properties and matching the liquid arranged on the substrate 11. For example, if the liquid to be arranged on the substrate 11 is a water-based coating, the substrate 11 uses a hydrophilic material; if the liquid to be arranged on the substrate 11 is an oil-based coating, the substrate 11 uses an oleophilic material to facilitate the even spreading of the liquid on the substrate 11.

[0112] In one embodiment, the substrate 11 can be made of a transparent material, such as Figure 5As shown, the detection device 41 is placed above the reaction platform 3, and the substrate 11 passes through between the detection device 41 and the reaction platform 3. The substrate 11 is made of a transparent material, facilitating the detection device 41 to detect the sample on the reaction platform 3 through the substrate 11 to obtain the biometric information of the sample.

[0113] In another embodiment, the substrate 11 can also be made of other non-transparent or semi-transparent materials, such as Figure 6 As shown, at this time, the detection device 41 is arranged elsewhere, and the sample carrier 32 on the reaction platform 3 is transferred between the reaction platform 3 and the detection device 41 through a transfer device 43 (such as a robotic arm), so that the sample on the sample carrier 32 reacts on the reaction platform 3 and is detected at the detection device 41 to obtain the biometric information of the sample.

[0114] In yet another embodiment, multiple sample carriers 32 can share the reaction platform 3. When one sample carrier 32 is transferred to the detection device 41 for detection, another sample carrier 32 can be transferred to the reaction platform 3, and under the control of the control device 17, the liquid on the other sample carrier 32 is displaced using the substrate 11, so that the sample in the other sample carrier 32 undergoes a new round of reaction.

[0115] Please continue to refer to Figure 3 , the reaction platform 3 includes a stage 31 and a sample carrier 32 placed on the stage 31. The sample carrier 32 can be a biochip. The reaction platform 3 is arranged beside the path where the substrate 11 passes, and is spaced from the substrate 11. Please refer to Figure 7 With Figure 8 As shown, the distance between the substrate 11 and the sample carrier 32 is greater than zero but less than the sum of the thickness of the liquid layer H1 on the substrate 11 and the thickness of the liquid layer H2 on the sample carrier 32. By setting the distance between the substrate 11 and the sample carrier 32, when the substrate 11 takes away the liquid on the sample carrier 32, it does not contact the sample carrying information on the sample carrier 32, avoiding damage to the sample information. At the same time, the liquid carried on the substrate 11 can be mixed with the liquid on the sample carrier 32 to form an intermolecular force, facilitating the substrate 11 to take away the liquid on the sample carrier 32.

[0116] Please refer to Figure 9 As shown, in one embodiment, by arranging a spacer 321 facing the substrate 11 above the sample carrier 32, the spacer 321 is used to space the substrate 11 and the sample carrier 32, so that the distance between the substrate 11 and the sample carrier 32 satisfies Figure 3The distance requirements shown. Specifically, in the present embodiment, spacers 321 are provided at opposite ends of the sample carrier 32 respectively. Each spacer 321 is formed by applying glue or photoresist on the sample carrier 32 or other means. Glue can be mixed with particles of a known diameter to control the spacer 321 to a preset height. When pressing the colloid, a force sensor can be designed to determine the time to stop pressing.

[0117] Please refer to Figure 10 As shown, in another embodiment, by providing spacers 311 facing the substrate 11 on the stage 31, the substrate 11 and the sample carrier 32 are spaced apart by the spacers provided on the stage 31, so that the distance between the substrate 11 and the sample carrier 32 meets Figure 3 The distance requirements shown. Specifically, in the present embodiment, spacers 311 are provided at opposite ends of the stage 31 respectively. Each spacer 311 is formed by applying glue or installing spacer bars.

[0118] Using the spacers 311 / 321 not only facilitates maintaining the preset distance between the substrate 11 and the sample carrier 32, but also provides a sealing-like effect for the reaction between the sample and the liquid on the reaction platform 3, reducing the volatilization of the liquid and being beneficial to stabilizing the temperature required for the reaction between the sample and the liquid.

[0119] In some embodiments, a force away from the reaction platform 3 can also be applied to the substrate 11 to prevent the substrate 11 from bending and contacting the sample carrier 32 during movement. Please refer to Figure 11 and Figure 12 As shown, in one embodiment, an adsorption device is provided on the upper side of the substrate 11 away from the reaction platform 3, and the substrate 11 is negatively adsorbed by the adsorption device to prevent the substrate 11 from bending and contacting the sample carrier 32. The adsorption device can be, for example, Figure 11 The object plane 180 shown. A liquid layer 181 is coated on the object plane 180, and the liquid layer 181 adheres the substrate 11 to the object plane 180. Among them, the surface 1801 of the object plane 180 in contact with the substrate 11 is parallel to the moving direction of the substrate 11. The adsorption device can also be, for example, Figure 12 The vacuum adsorption device 182 shown. The surface 1821 of the vacuum adsorption device 182 in contact with the substrate 11 is parallel to the moving direction of the substrate 11.

[0120] Please return to refer to Figure 3 As shown, the liquid distribution device 13 includes a liquid storage device 132. The liquid storage device 132 can be a temperature-controlled storage device. According to the temperature required for the reaction of the stored liquid, the temperature-controlled storage device is controlled by the control device 17 to maintain the required temperature.

[0121] In another embodiment, the liquid storage device 132 is a non-temperature-controlled memory. In this case, for a liquid that requires a specific reaction temperature, during the process of the liquid flowing out of the liquid storage device 132 and onto the substrate 11, the liquid will be heated or cooled to a suitable temperature. For example, in the liquid distribution device 13, a separate temperature control device (not shown in the figure) is provided to heat or cool the liquid to a suitable temperature when it flows out onto the substrate 11.

[0122] In the third embodiment, as Figure 13 shown, a temperature control device 33 can be provided on the reaction platform 3, and the control device 17 controls the temperature control device 33 to heat or cool according to a preset time sequence, so that the liquid and the sample on the reaction platform 3 are at a suitable temperature for reaction each time. The heating / cooling method can use a thermoelectric cooler (TEC) or other methods with rapid temperature rise and fall.

[0123] To avoid heating and losing the liquid, which may affect the sample reaction. For example, when the temperature control device 33 on the reaction platform 3 heats the liquid, in one embodiment, according to the different required reaction temperatures, the length of some liquid arranged on the substrate 11 is appropriately extended. After the substrate 11 moves to replace the liquid on the reaction platform 3 with new liquid, the control device 17 still controls the substrate 11 to move slowly to continuously provide new liquid for the reaction platform 3 to supplement the liquid lost due to heating or prevent drying. In another embodiment, the reaction platform 3 can be set as a movable platform that can move away from and close to the substrate 11. When the liquid is heated for reaction, the control device 17 controls the reaction platform 3 to approach the substrate 11 by a certain distance, so that the substrate 11 and the sample carrier 32 directly form a similar sealing effect to prevent the evaporation of the liquid during the reaction. Similarly, in yet another embodiment, please refer to Figure 14 shown, a pressing device 183 can be provided above the substrate 11 away from the reaction platform 3. The pressing device 183 moves down a certain distance under the control of the control device 17 to push the substrate 11 closer to the reaction platform 3 by a certain distance, so that the substrate 11 and the sample carrier 32 directly form a similar sealing effect to prevent the evaporation of the liquid during the reaction. Therefore, according to the required temperature of the liquid participating in the reaction, the control device 17 decides whether to activate the pressing device 183 to push down the substrate 11 or decides whether to move up the reaction platform 3.

[0124] In this embodiment, at the rear end of the moving path of the substrate 11, a liquid cleaning device is also provided. In one embodiment, please refer to Figure 15 shown, the liquid cleaning device is a dryer 184. After the substrate 11 passes through the reaction platform 3, it then passes through the dryer 184, and the dryer 184 is turned on to dry the residual liquid H3 on the substrate 11. In another embodiment, please refer to Figure 16As shown, the liquid removal device is a squeegee 185. The top of the squeegee 185 contacts the substrate 11 to scrape off the residual liquid H3 on the substrate 11, and the scraped liquid drips into the waste bucket 186 placed below the squeegee 185. In another embodiment, the squeegee 185 and the dryer 184 can be provided simultaneously. The liquid not scraped off by the squeegee 185 is dried by the dryer 184, or the liquid not dried by the dryer 184 is scraped off by the squeegee 185. In this way, by removing the residual liquid, the pollution, corrosion, etc. of the contacted devices and components by the residual liquid are avoided.

[0125] In one embodiment, please refer to Figure 17 As shown, a leveling device 187 can also be provided at the front end of the moving path of the substrate 11. After the liquid is arranged on the substrate 11, it is leveled by the leveling device 187 before being transferred to the sample carrier 32. In one embodiment, the leveling device 187 is a squeegee.

[0126] In some embodiments, some auxiliary means can also be used to enhance the efficiency of removing / replacing the liquid on the substrate 11 from the reaction platform 3. For example, sound waves, lasers or magnets are used to drive the liquid between the substrate 11 and the sample carrier 32. For example, acceleration devices such as sound waves, lasers or magnetic acceleration are provided above the substrate 11 and / or below the sample carrier 32 (not shown in the figure) to accelerate the efficiency of removing the liquid on the substrate 11 from the reaction platform 3.

[0127] The control device 17 controls the driving device to control the start, stop and moving speed of the substrate 11, controls the tensioning device 15 to cooperate with the liquid distribution on each section of the substrate 11, and controls the liquid distribution device 13 to arrange the liquid on the substrate 11 according to the preset timing and the amount of the arranged liquid (thickness and length). In this embodiment, the thickness of the liquid arranged on the substrate 11 is below 200 microns to avoid the liquid dripping due to too thick liquid or the need for too long substrate 11 to carry away the liquid in the previous stage and replace the liquid in the next stage due to too thin liquid. Further, when a temperature-controlled memory is adopted, the control device 17 controls the temperature of the temperature-controlled memory according to the temperature required for each liquid reaction. When a temperature control device is adopted, the control device 17 controls the temperature control device to heat or cool to a suitable temperature according to the temperature required for each liquid reaction in combination with the preset timing. When multiple sample carriers share the reaction platform 3, the liquid arrangement on the substrate 11, the liquid reaction of each sample carrier, the transfer and detection of each sample carrier, etc. are controlled according to each sample carrier and its preset timing. When the substrate 11 or the reaction platform 3 can approach and move away from each other, the control device controls the substrate 11 and the reaction platform 3 to approach or move away according to the liquid participating in the reaction. When a device for enhancing the efficiency of liquid removal / replacement is provided, the start, stop and even the output power of the device are controlled. In short, according to the need, the control device 17 can control the components to be controlled and their operating rules.

[0128] It can be understood that the control device 17 can also be divided into multiple sub-control devices (not shown in the figure), and each sub-control device is used to implement a part of all controls. The sub-control devices can communicate with each other to facilitate collaborative operations.

[0129] In this embodiment, under the control of the control device 17, the substrate 11 is driven by the driving device 14 to move in one direction. When the substrate 11 passes through the die head 131, the die head 131 uniformly covers one or more liquids in the liquid storage device 132 onto a part or all of the area of the substrate 11 in the width direction with a certain length and thickness; when the substrate 11 passes parallel to the reaction platform 3 at a certain speed or speed combination and at a certain height, the liquid covered thereon contacts the sample carrier 32; the substrate 11 continues to move, and fresh liquid or other types of liquid continue to contact the sample carrier 32 to replace the original liquid, so that the reaction continues (the fresh liquid and the original liquid are the same liquid, and at this time it is a supplementary liquid) or other reactions occur (the fresh liquid and the original liquid are not the same liquid); after the predetermined reaction is completed, the sample carrier 32 is detected in situ (i.e., detected at the reaction platform 3), or the sample carrier 32 is transferred to the detection device 41 for detection. Using the moving substrate 11 to replace the liquid for the sample carrier 32 can achieve the coating of extremely thin liquids (such as reagents), greatly saving liquids and improving the utilization rate of liquids; in addition, it makes the replacement of liquids more rapid, and since the substrate can be a coil and does not require installation, it greatly improves the throughput of biological property determination. Furthermore, by negatively adsorbing the substrate 11 and / or using spacers 311 / 321 to space the substrate 11 and the sample carrier 32, scratching of the sample carrier 32 is avoided, and since the substrate 11 is not brittle glass, the problem of cracking of the upper plate of the flow cell does not occur when the speed of flowing the fluid onto the substrate 11 is increased, avoiding damage to the sample. At the same time, by adjusting the timing, multiple sample carriers 32 can share the liquid transfer device 1, and the detection and reaction times of different sample carriers can overlap, thereby further saving time and cost and improving the overall performance of the device. In addition, the materials of other components of the liquid transfer device 1 that contact the liquid can be titanium, Hastelloy, or polymer materials to prevent the liquid and electrolyte from rusting the contacting components or dissolving in the liquid.

[0130] Example Two

[0131] Please refer to Figure 18 As shown in the figure, it is a schematic diagram of some components of the liquid transfer device in Example Two. The liquid transfer device 2 includes a plurality of substrates 21. The plurality of substrates share a liquid distribution device 23. The die head 231 of the liquid distribution device 23 is arranged on a guide rail 232 and moves between the plurality of substrates 21 along the guide rail 232 to distribute liquid to each substrate 21 according to a preset timing. In Figure 18In the illustrated embodiment, the die head 231 can move between a first position A, a second position B, and a third position C to dispense liquid for three substrates 21. Since the settings of other parts of the liquid transfer device 2 can refer to the liquid transfer device 1, and moreover, the functions that the liquid transfer device 2 can achieve and the beneficial effects that can be achieved can also refer to the liquid transfer device 1, the introduction thereof is omitted here.

[0132] Embodiment III

[0133] Please refer to Figure 19 As shown, the liquid transfer device 5 in Embodiment III includes a substrate 51, a driving device 54, and a control device 57. Under the control of the control device 57, the driving device 54 drives the substrate 51 to move in one direction. The substrate 51 is driven to pass above the reaction platform 3 to carry away the liquid on the sample carrier 32. In this embodiment, the control device 57 or other control devices can control a transfer device (not shown in the figure) to place different sample carriers 32 on the stage 31, and use the substrate 51 to carry away the liquid on different sample carriers 32. For each sample carrier 32, a certain amount of liquid can be previously dispensed on the surface of the sample carrier 32 by using a die head (not shown in the figure) or other similar liquid dispensing devices such as an inkjet head. After using the substrate 51 to carry away the liquid on a sample carrier 32, in-situ detection is performed on the sample carrier 32, or alternatively, the sample carrier 32 is transferred to a detection device (not shown in the figure) for detection through the transfer device.

[0134] In this embodiment, the arrangement of each component in the liquid transfer device 5 and the arrangement of the reaction platform 3 can refer to Embodiment I.

[0135] In other embodiments, the liquid transfer device 5 may further include a liquid dispensing device (not shown in the figure) to coat a buffer solution or some reaction reagents on the substrate 51.

[0136] Compared with Embodiment I, in Embodiment III, at least part of the liquid is directly dispensed onto the sample carrier 32, rather than completely carried to the sample carrier 32 by the substrate 51. In this way, one substrate 51 can be responsible for wiping the liquid of multiple sample carriers 32.

[0137] Embodiment IV

[0138] Please refer to Figure 20 As shown, in this embodiment, the liquid transfer device 6 includes a substrate 61, a liquid dispensing device 63, a driving device 64, a guiding device 66, and a control device 67. The liquid dispensing device 63 is a printing device 631. The printing device 631 is similar to an existing printer, and the main difference is that the printing device 631 has no drying function. The printing device 631 prints different liquids onto the surface of the substrate 61 by means of electrostatic adsorption or magnetic adsorption. Please also refer to Figure 21As shown, the printing device 631 may include a storage device 6311 and a control device 6312. Control parameters such as the preset timing for controlling the printing liquid can be pre-stored in the storage device 6311. During the printing process, the control device 6312 reads the control parameters from the storage device 6311 and controls the printing device 6313 to perform the liquid printing task. In other embodiments, the control device 6312 may communicate with the control device 67 through a communication device (not shown in the figure) and receive the control of the control device 67 in real time. The liquid transfer device 6 further includes a driving device 64 and a guiding device 66. In this embodiment, the guiding device 66 is a guide rail 661. The driving device 64 drives the substrate 61 to move along the guide rail 661, and the control device 67 synchronizes the driving device 64 and the printing device 631.

[0139] In this embodiment, other settings of the liquid transfer device 6 and its relative positions with the reaction platform 3 can refer to Embodiment 1 and will not be elaborated here.

[0140] Embodiment 5

[0141] Please refer to Figure 22 As shown, in this embodiment, the liquid transfer device 7 includes a substrate 71, a liquid distribution device 73, a driving device 74, and a control device 77. The liquid distribution device 73 is a gravure roll 731. The gravure roll 731 is driven by a driving device 74 controlled by the control device 77 to distribute liquid on the substrate 71. The gravure roll 731 has a plurality of prefabricated patterns 7311, and the liquid to be distributed on the substrate 71 is pre-placed in the prefabricated patterns 7311. The driving device 74 is controlled by the control device 77 to drive the substrate 71 to move in one direction to pass through the reaction platform 3, and transfer the liquid on the substrate 71 to the sample carrier 32 of the reaction platform 3 to promote the reaction of the sample on the sample carrier 32. In other embodiments, the liquid distribution device 73 may be a screen printing device, and the liquid is coated on the substrate 71 by screen printing.

[0142] Embodiment 6

[0143] Embodiment 6 provides a biochemical substance reaction device. Please refer to Figure 23 As shown, the biochemical substance reaction device 8 includes a liquid transfer device 81 and a reaction platform 3. The liquid transfer device 81 is used for liquid transfer between the sample carrier 32 of the reaction platform 3. The liquid transfer includes transferring the liquid on the moving substrate to the sample carrier 32 and / or transferring the liquid on the sample carrier 32 to the moving substrate. The liquid transfer device 81 may be the liquid transfer device described in any of the above embodiments.

[0144] Embodiment 7

[0145] Embodiment VII provides a biochemical substance analysis device. Please refer to Figure 24 As shown, the biochemical substance analysis device 9a includes the biochemical substance reaction device 8 and the detection device 41 in Embodiment VI. The detection device 41 is used to perform signal detection on the sample on the sample carrier 32 to obtain the biological characteristic information of the sample.

[0146] Embodiment VIII

[0147] Please refer to Figure 25 As shown, compared with Embodiment VII, the biochemical substance analysis device 9b provided in Embodiment VIII further includes a transfer device 43. The transfer device 43 is used to transfer the sample carrier 32 on the reaction platform 3 between the reaction platform 3 and the detection device 41, so that the sample on the sample carrier 32 reacts at the reaction platform 3 and signal detection is performed at the detection device 41.

[0148] Embodiment IX

[0149] Embodiment IX provides a liquid transfer method, and the liquid transfer method can be implemented by using the liquid transfer device in the above embodiments. Please refer to Figure 26 As shown, the liquid transfer method includes step S2601 of controlling the substrate to move towards the direction where the reaction platform is located. The reaction platform includes a sample carrier carrying a sample; and step S2602 of controlling the substrate to pass through the reaction platform so that liquid transfer occurs between the moving substrate and the sample carrier. The liquid transfer is to transfer the liquid on the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate.

[0150] Further, in other embodiments, the liquid transfer method may further include the step of disposing liquid on the substrate; or, disposing liquid on the moving substrate, and the liquid is used for the above liquid transfer between the substrate and the sample carrier. The way of disposing the liquid is coating, printing or spraying.

[0151] Further, in other embodiments, disposing liquid on the substrate includes disposing a variety of liquids on the substrate according to a preset time sequence. The variety of liquids are connected end to end. Specifically, the variety of liquids include a buffer reagent and two or more reaction reagents, and the buffer reagent connects the two reaction reagents distributed front and back on the substrate. Or, further, the head and tail ends of the buffer reagent are respectively stacked with the ends of the reaction reagents located in the front and back.

[0152] Further, in other embodiments, the thickness of the liquid disposed on the substrate is less than 200 microns.

[0153] Further, in other embodiments, the liquid transfer method may further include the step of disposing a liquid on the sample carrier. The liquid is used for the above-mentioned liquid transfer between the substrate and the sample carrier. The liquid is disposed by coating or spraying.

[0154] Embodiment Ten

[0155] Embodiment Ten provides a biochemical substance analysis method, and the biochemical substance reaction method can be implemented by using the biochemical substance reaction device in the above embodiments. Please refer to Figure 27 As shown, the biochemical substance reaction method includes step S2701 of controlling the movement of the substrate towards the direction where the reaction platform is located, where the reaction platform includes a sample carrier carrying a sample; step S2702 of controlling the substrate to pass through the reaction platform so that liquid transfer occurs between the moving substrate and the sample carrier, and the liquid transfer is to transfer the liquid on the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate; and step S2703 of, after waiting for the sample on the sample carrier to react with the liquid, performing detection on the sample that has completed the reaction.

[0156] Further, in other embodiments, the liquid transfer method may further include the step of disposing a liquid on the substrate. The liquid is used for the above-mentioned liquid transfer between the substrate and the sample carrier. The liquid is disposed by coating, printing or spraying.

[0157] Further, in other embodiments, disposing a liquid on the substrate includes: disposing a plurality of liquids on the substrate according to a preset time sequence. The plurality of liquids are connected end to end. Specifically, the plurality of liquids include a buffer reagent and two or more reaction reagents, and the buffer reagent connects two reaction reagents distributed front and back on the substrate. Or, further, the two ends of the buffer reagent are respectively overlapped with the ends of the reaction reagents located front and back.

[0158] Further, in other embodiments, the thickness of the liquid disposed on the substrate is less than 200 microns.

[0159] Further, in other embodiments, the liquid transfer method may further include the step of disposing a liquid on the sample carrier. The liquid is used for the above-mentioned liquid transfer between the substrate and the sample carrier. The liquid is disposed by coating or spraying.

[0160] Further, in other embodiments, step S2703 further includes: transferring the sample carrier to a detection device so that the detection device performs the detection on the sample.

[0161] The beneficial effects of the above embodiments can all refer to the description of the beneficial effects in Embodiment One, and will not be elaborated here.

[0162] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A liquid transfer device for liquid transfer between a sample carrier of a reaction platform, characterized in that, It includes a substrate, a driving device and a control device. The control device is used to control the driving device to drive the substrate to move towards the reaction platform, so that the moving substrate passes through the sample carrier and liquid transfer occurs between the substrate and the sample carrier. The liquid transfer is to transfer the liquid carried by the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate. The liquid transfer device further includes a liquid dispensing device, and the liquid dispensing device is used to dispense liquid onto the substrate, or the liquid dispensing device is used to dispense multiple liquids onto the substrate according to a preset time sequence.

2. The liquid transfer device according to claim 1, characterized in that, The liquid dispensing device includes a liquid outlet mechanism, a fluid power module, a valve device and a liquid storage device. The fluid power module and the valve device are used to receive the control of the control device to control the liquid to flow out of the liquid storage device and be dispensed onto the substrate through the liquid outlet mechanism.

3. The liquid transfer device according to claim 2, wherein, The liquid outlet mechanism is a die head, and the die head dispenses the liquid onto the substrate by coating.

4. The liquid transfer device according to claim 1, wherein, The liquid dispensing device is a printing device, and the printing device dispenses the liquid onto the substrate by printing; or the liquid dispensing device is an anilox roll or a screen printing device.

5. The liquid transfer device according to claim 1, wherein The thickness of the liquid dispensed by the liquid dispensing device onto the substrate is less than 200 microns.

6. The liquid transfer device according to claim 1, wherein When the liquid dispensing device dispenses multiple liquids onto the substrate, the multiple liquids are connected front and back on the substrate; or the multiple liquids include a reaction reagent and a buffer reagent, and the buffer reagent connects the reaction reagents located front and back; or the head and tail ends of the buffer reagent are respectively stacked with the ends of the reaction reagents located front and back.

7. The liquid transfer device according to claim 1, characterized in that, The liquid dispensing device includes a liquid storage device, and the liquid storage device is a temperature-controlled memory.

8. The liquid transfer device according to claim 1, wherein The substrate is a coil, or the substrate is a transparent material, or the hydrophilicity, hydrophobicity, lipophilicity and lipophobicity of the substrate are adapted to the properties of the liquid.

9. The liquid transfer device according to claim 1, wherein, The distance between the substrate and the sample carrier is greater than zero but less than the sum of the thickness of the liquid on the substrate and the thickness of the liquid on the sample carrier.

10. The liquid transfer device according to claim 1, wherein, It further includes an adsorption device, and the adsorption device is located on the side of the substrate away from the reaction platform. The adsorption device is used to adsorb the substrate to prevent the substrate from bending and contacting the sample carrier.

11. The liquid transfer device according to claim 10, characterized in that, The adsorption device is an object plane coated with a liquid layer. The surface of the object plane in contact with the substrate is coated with the liquid layer and is parallel to the moving direction of the substrate. The object plane adsorbs the substrate through the liquid layer; or the adsorption device is a vacuum adsorption device, and the surface of the vacuum adsorption device in contact with the substrate is parallel to the moving direction of the substrate.

12. The liquid transfer device according to claim 1, wherein, It further includes a pressing device arranged on the side of the substrate away from the reaction platform. The pressing device is used to press the substrate to form a sealing effect between the substrate and the sample carrier to prevent liquid evaporation.

13. The liquid transfer device according to claim 12, wherein, The control device is further used to determine whether to start the pressing device to press the substrate according to the temperature required by the liquid participating in the reaction on the sample carrier.

14. The liquid transfer device according to claim 1, wherein, It further includes a liquid cleaning device arranged at the rear end of the moving path of the substrate. The liquid cleaning device is used to clean the liquid remaining on the substrate after the substrate passes through the sample carrier.

15. The liquid transfer device according to claim 14, wherein The liquid removal device is a dryer and / or a squeegee.

16. The liquid transfer device according to claim 1, wherein, Further included is a flattening device disposed at the front end of the moving path of the substrate. The flattening device is used to flatten the liquid after the liquid is disposed on the substrate and before it is transferred to the sample carrier.

17. The liquid transfer device according to claim 16, wherein The flattening device is a squeegee.

18. The liquid transfer device according to claim 1, wherein, Further included is an accelerating device used to accelerate the liquid transfer between the substrate and the sample carrier.

19. The liquid transfer device according to claim 18, wherein, The accelerating device is an acoustic wave, a laser, and / or a magnetic acceleration device.

20. The liquid transfer device according to claim 1, wherein, There are multiple substrates, and the multiple substrates share the liquid dispensing device. The liquid dispensing device includes a liquid outlet mechanism, and the liquid outlet mechanism is controlled by a control device to move along a guide rail to dispense liquid onto the multiple substrates.

21. A biochemical substance reaction device, characterized in that, Including the liquid transfer device according to any one of claims 1 - 20 and a reaction platform, the reaction platform includes a sample carrier for loading a sample.

22. The biochemical substance reaction device according to claim 21, wherein, The reaction platform is a movable platform that can move away from and reliably approach the substrate. The control device is further used to determine whether to start moving the reaction platform according to the temperature required for the liquid participating in the reaction on the sample carrier.

23. The biochemical substance reaction device according to claim 21, wherein, A spacer facing the substrate is provided on the reaction platform, and the spacer spaces the distance between the substrate and the reaction platform.

24. The biochemical substance reaction device according to claim 23, wherein, The reaction platform further includes a stage, and the spacer is disposed on the stage, or the spacer is disposed on the sample carrier.

25. The biochemical substance reaction device according to claim 24, wherein, The spacer is disposed on the reaction platform by means of gluing or photoresist.

26. The biochemical substance reaction device according to claim 21, wherein A temperature control device is provided on the reaction platform, and the control device is further used to control the temperature control device to heat or cool according to the temperature required for the liquid undergoing the reaction.

27. The biochemical substance reaction device according to claim 21, wherein, An accelerating device is further provided on the reaction platform, and the accelerating device is used to accelerate the liquid transfer between the substrate and the reaction platform.

28. The biochemical substance reaction device according to claim 27, characterized in that, The accelerating device is an acoustic wave, a laser, and / or a magnetic acceleration device.

29. A biochemical substance analysis device, characterized in that, Including the biochemical substance reaction device and the detection device according to any one of claims 21 - 28.

30. The biochemical substance analysis device according to claim 29, characterized in that, The detection device is used to perform detection on the sample on the sample carrier through the substrate.

31. The biochemical substance analysis device according to claim 29, wherein Further included is a transfer device used to transfer the sample carrier between the biochemical substance analysis device and the detection device.

32. A liquid transfer method, characterized in that, Including: Controlling the substrate to move in the direction where the reaction platform is located, the reaction platform including a sample carrier for carrying a sample; and Controlling the substrate to pass through the reaction platform and perform liquid transfer between the substrate and the sample carrier. The liquid transfer is to transfer the liquid on the substrate to the sample carrier and / or transfer the liquid on the sample carrier to the substrate. The method further includes: disposing liquid on the substrate; Or, disposing liquid on the moving substrate. The liquid is used for the above liquid transfer between the substrate and the sample carrier. Disposing liquid on the substrate is to dispose multiple liquids on the substrate according to a preset time sequence.

33. The liquid transfer method according to claim 32, wherein The way of disposing the liquid is coating, printing, or spraying.

34. The liquid transfer method according to claim 32, wherein The multiple liquids are connected end to end.

35. The liquid transfer method according to claim 34, characterized in that, The multiple liquids include a buffer reagent and two or more reaction reagents, and are connected by the buffer reagent between the two reaction reagents distributed front and back on the substrate; alternatively, the two ends of the buffer reagent are respectively stacked with the ends of the reaction reagents located in the front and back.

36. The liquid transfer method according to claim 32, wherein, The thickness of the liquid disposed on the substrate is less than 200 microns.

37. The liquid transfer method according to claim 32, wherein, The method further includes: disposing a liquid on the sample carrier, and the liquid is used for the above liquid transfer between the substrate and the sample carrier.

38. The liquid transfer method according to claim 34, wherein, The manner of disposing the liquid is coating or spraying.

39. A method for analyzing biochemical substances, characterized in that, Comprising: The liquid transfer method according to any one of claims 32-38; and After waiting for the sample on the sample carrier to react with the liquid, performing detection on the sample.

40. The biochemical substance analysis method according to claim 39, characterized in that, Further comprising: Transferring the sample carrier to a detection device so that the detection device performs the detection.

Citation Information

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    CN1944674A