Microfluidic liquid transfer system, microfluidic liquid transfer method and applications

Abstract

This invention discloses a micro-volume liquid transfer system, a micro-volume liquid transfer method, and its application. The micro-volume liquid transfer system includes: a reservoir for storing the liquid to be transferred; a pipette tip made of a conductive material for picking up and transferring the liquid from the reservoir; a receiver made of a conductive material for receiving the liquid transferred by the pipette tip; a power supply electrically connected to the pipette tip for energizing the pipette tip to create a voltage difference between the pipette tip and the receiver; a controller electrically connected to the power supply for controlling the energization or de-energization of the pipette tip; and a drive assembly for driving the pipette tip to move, or for driving at least two of the movements of the reservoir, pipette tip, and receiver. The micro-volume liquid transfer system of this invention can transfer micro-volume liquids, is simple, fast, efficient, reliable, and accurate.

Description

Technical Field

[0001] This invention belongs to the field of micro-liquid transfer technology, specifically relating to a micro-liquid transfer system, a micro-liquid transfer method, and its applications. Background Technology

[0002] Micro-liquid transfer technology is a technique that moves a small amount (range 100nL-10pL), precisely (±10μm), precisely (±10%), and without contamination, of liquid stored in a specific container (such as a well plate or centrifuge tube) to a target location. It has wide applications in the fields of biology, medicine, and chemistry.

[0003] Biosample microarray printing is fundamental to biochip fabrication. Through printing technology, large quantities of different types of biological samples can be printed onto planar substrates (such as glass slides, the bottom surface of well plates, etc.) to form microarrays, which can then be used for subsequent detection. Existing microarray printing technologies include contact printing, piezoelectric inkjet printing, and ultrasonic printing.

[0004] Contact printing directly uses the liquid contact surface of the needle tip. Its advantages are: simple structure, high stability, and the instrument is not easily damaged. Batch printing can be achieved by integrating a large number of printing needles into an array. However, the problems are that the volume of the printing liquid is uncontrollable and the single-channel printing speed is relatively slow.

[0005] Piezoelectric inkjet printing uses the same technical principle as common inkjet printers. It modulates the movement of piezoelectric ceramics in the printhead by adjusting the pressure, which forces liquid in microchannels to be ejected as ink. The advantages of piezoelectric inkjet printing are: inkjet printing, printable volume less than 100 pL, fast printing speed, and high precision, but it has the problem of complex sampling.

[0006] Ultrasonic printing works by applying ultrasonic waves to the bottom of a perforated plate. The ultrasonic energy precisely excites a drop of liquid to fly out and reach the surface. The advantages of ultrasonic printing are that it requires no special printhead, requires zero cleaning, and is high-speed. However, it has limitations in terms of minimum print volume (approximately 1 nL) and lower print accuracy. Summary of the Invention

[0007] The purpose of this invention is to provide a micro-liquid transfer system, a micro-liquid transfer method and application, which can transfer micro-liquids in a simple, fast and efficient manner with high reliability and accuracy.

[0008] To achieve the above objectives, a specific embodiment of the present invention provides the following technical solution:

[0009] A micro-liquid transfer system, the micro-liquid transfer system comprising:

[0010] A liquid storage container is used to store liquids to be transferred.

[0011] A pipette tip, made of conductive material, is used to pick up and transfer liquid from a reservoir.

[0012] A receiver, made of a conductive material, is used to receive liquid transferred by a pipette tip;

[0013] A power supply, electrically connected to the pipette tip, is used to energize the pipette tip and create a voltage difference between the pipette tip and the receiver.

[0014] The controller, electrically connected to the power supply, is used to control the power supply to or from the pipette tip.

[0015] A drive assembly for driving the movement of a pipette tip, or for driving the movement of at least two of a reservoir, a pipette tip, and a receiver.

[0016] In one or more embodiments of the present invention, the pipette is a solid needle or slit needle made of metal, a solid needle or slit needle made of non-metallic material, a solid needle or slit needle made of ceramic material, a solid needle or slit needle made of plastic material, or a multi-material needle obtained by splicing different parts of needles made of metal, non-metallic material, ceramic material, and plastic material, or a tubular structure made of metal, non-metallic material, ceramic material, and plastic material.

[0017] In one or more embodiments of the present invention, the solid needle has a diameter of 200 μm-2 mm, a needle tip angle of 10°-60°, and a tip end face that is a platform with a diameter of 1 μm-1000 μm; and / or,

[0018] The slit needle has a diameter of 200μm-2mm, a needle tip angle of 10°-60°, and a platform with a diameter of 1μm-1000μm at the tip. A slit with a width of 1μm-500μm is provided at the needle tip; and / or,

[0019] The tubular structure has an outer diameter of 2μm-2mm and an inner diameter of 1μm-1mm.

[0020] In one or more embodiments of the present invention, a plurality of pipette tips are provided, and the plurality of pipette tips are arranged in an array.

[0021] In one or more embodiments of the present invention, the micro-liquid transfer system further includes a working platform, the driving component includes a Z-axis worktable and a Z-axis moving stage disposed on the Z-axis worktable, the Z-axis worktable is provided with a Z-axis motor for driving the Z-axis moving stage to rise and fall, and the pipetting head is disposed on the Z-axis moving stage.

[0022] In one or more embodiments of the present invention, the working platform is further provided with an X-axis working table and a Y-axis working table, the X-axis working table is provided with an X-axis motor, and the Y-axis working table is provided with a Y-axis motor;

[0023] Wherein, the Y-axis worktable is mounted on the X-axis worktable, the X-axis motor drives the Y-axis worktable to move, a mounting platform is provided on the Y-axis worktable, the Y-axis motor drives the mounting platform to move, and the liquid reservoir and receiver are mounted on the mounting platform; or

[0024] The X-axis worktable is mounted on the Y-axis worktable, the Y-axis motor is used to drive the X-axis worktable to move, the X-axis worktable is provided with a mounting platform, the X-axis motor is used to drive the mounting platform to move, and the liquid reservoir and receiver are mounted on the mounting platform.

[0025] In one or more embodiments of the present invention, the micro-liquid transfer system further includes a measurement component, the measurement component including a bottom-up distance sensor and a top-down distance sensor;

[0026] The bottom-up distance sensor is mounted on the mounting platform and is used to measure the position error of the pipette tip.

[0027] The top-down distance sensor is mounted on the Z-axis worktable and is used to measure the position of the mounting platform, the position and error of all components on the mounting platform, and the liquid level in the liquid reservoir.

[0028] In one or more embodiments of the present invention, the bottom-up distance sensor and the top-down distance sensor are selected from contact distance sensors, ultrasonic distance sensors, reflective optical distance sensors, confocal optical distance sensors, interferometric optical distance sensors, and time-of-flight optical distance sensors.

[0029] In one or more embodiments of the present invention, the micro-liquid transfer system further includes an optical imaging system disposed on a Z-axis worktable, the optical imaging system including at least an illumination source and a camera.

[0030] In one or more embodiments of the present invention, the micro-liquid transfer system further includes a capacitance measuring device connected to a power source, the capacitance measuring device being used to measure the capacitance between the pipette tip and the reservoir, and between the pipette tip and the receiver.

[0031] In one or more embodiments of the present invention, the micro-liquid transfer system further includes an environmental control component, which includes a closed container and a temperature control system, a humidity control system, a dust removal system, a gas circulation system, and a gas injection system connected to the closed container;

[0032] The enclosed container is used to house at least the reservoir, pipette tip, receiver, and drive assembly.

[0033] Another specific embodiment of the present invention provides the following technical solution:

[0034] A method for transferring micro-volume liquids, the method using a micro-volume liquid transfer system, specifically includes the following steps:

[0035] Use the drive assembly to move the pipette tip, or move at least two of the reservoir, pipette tip, and receiver, so that the pipette tip picks up the liquid in the reservoir;

[0036] Bring the pipette tip and receiver close to each other;

[0037] Powering the pipette tip creates a voltage difference between it and the receiver, causing the liquid on the pipette tip to be sprayed onto the receiver, thus completing the liquid transfer.

[0038] In one or more embodiments of the present invention, the voltage difference between the pipette tip and the receiver is 0.5kV-5kV.

[0039] In one or more embodiments of the present invention, the output voltage of the power supply is 0.5kV-5kV;

[0040] The receiver is connected to a ground wire.

[0041] Another specific embodiment of the present invention provides the following technical solution:

[0042] Application of a micro-liquid transfer system or method in the micro-array printing of biological samples.

[0043] In one or more embodiments of the present invention, the printing solvent is at least one of an aqueous solvent, an organic solvent, or a mixture of an aqueous solvent and an organic solvent.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] 1. This invention uses solid needles, slit needles, and capillary tubes without pressurized ink supply for electrostatic inkjet printing or micro-volume pipetting via dipping, achieving pipetting at the 100pL level with high stability and precision. Furthermore, this invention employs a reservoir in the form of a multi-hole plate to store ink, making replacement simple and convenient, thus solving the problem of traditional electrostatic inkjet printing's inability to easily replace ink.

[0046] 2. The micro-liquid transfer system of the present invention is simple, without overly complex structure and control logic, has high reliability, fast and efficient printing speed, and is easy to maintain. The pipette head used can be independently disassembled and replaced, which solves the problems of traditional electrostatic inkjet printing, such as complex structure, large space occupation, and inability to achieve batch printing through array pipette heads. Attached Figure Description

[0047] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0048] Figure 1 This is a schematic diagram of the structure of a micro-liquid transfer system in one embodiment of the present invention;

[0049] Figure 2 for Figure 1 Enlarged view of section A;

[0050] Figure 3 This is a schematic diagram of the pipette head in one embodiment of the present invention;

[0051] Figure 4 This is an end face view of the pipette tip in one embodiment of the present invention;

[0052] Figure 5 This is a schematic diagram of a micro-liquid transfer method in one embodiment of the present invention.

[0053] Explanation of key figure labels:

[0054] 1. Working platform; 21. X-axis worktable; 22. X-axis motor; 23. Mounting platform; 24. Liquid reservoir; 25. Receiver; 31. Y-axis worktable; 32. Y-axis motor; 41. Z-axis worktable; 42. Z-axis moving stage; 43. Z-axis motor; 5. Pipette head; 51. Gap needle; 52. Gap; 53. Platform; 61. Host computer; 62. Sub-computer; 71. Top-down distance sensor; 72. Bottom-up distance sensor; 73. Optical imaging system. Detailed Implementation

[0055] To enable those skilled in the art to better understand the technical solutions in this disclosure, the technical solutions in the embodiments of this disclosure are described clearly and completely below. Obviously, the described embodiments are only some embodiments of this disclosure, and not all embodiments. Based on the embodiments in this disclosure, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this disclosure.

[0056] Example 1

[0057] like Figure 1 As shown, the present invention discloses a micro-liquid transfer system for printing biological sample microarrays, specifically including a working platform 1, on which an X-axis worktable 21, a Y-axis worktable 31 and a Z-axis worktable 41 are provided.

[0058] Furthermore, in combination Figure 2 The X-axis worktable 21 is mounted on the Y-axis worktable 31. The Y-axis worktable 31 is equipped with a Y-axis motor 32 for driving the X-axis worktable 21 to move along the Y-axis direction. The X-axis worktable 21 is equipped with a mounting platform 23 and an X-axis motor 22 for driving the mounting platform 23 to move along the X-axis direction. The movement of the mounting platform 23 in the X-axis and Y-axis directions is achieved through the X-axis worktable 21 and the Y-axis worktable 31.

[0059] Furthermore, in other embodiments, the Y-axis worktable 31 can be placed on the X-axis worktable 21, and the mounting platform 23 can be placed on the Y-axis worktable 31. The X-axis motor 22 is used to drive the Y-axis worktable 31 to move, and the Y-axis motor 32 is used to drive the mounting platform 23 to move, thereby realizing the movement of the mounting platform 23.

[0060] Furthermore, the Z-axis stage 41 is equipped with a Z-axis moving stage 42 and a Z-axis motor 43 for driving the Z-axis moving stage 42 to move up and down. The Z-axis moving stage 42 is equipped with pipette heads 5 arranged in an array. The rows and columns of the array of pipette heads 5 are parallel to the X-axis and Y-axis directions of the X-axis motor 22 and Y-axis motor 32, respectively. The row and column spacing of the array is the spacing of the orifice plates, such as 4.5 mm for 384-well plates and 2.25 mm for 1536-well plates. The 4.5 mm row and column spacing is compatible with both 384-well and 1536-well plate spacings. Furthermore, the number of rows in the array of pipette heads 5 is divisible by the number of rows in the orifice plate, and the same applies to the number of columns.

[0061] Furthermore, the pipette tip 5 is made of a conductive material, specifically a solid or slotted needle made of metal, such as steel, titanium alloy, nickel alloy, cobalt alloy, etc.; a solid or slotted needle made of non-metallic materials, such as carbon, silicon, etc.; a solid or slotted needle made of ceramic materials, such as alumina, aluminum nitride, boron nitride, zirconium oxide, silicon nitride, silicon carbide, etc.; a solid or slotted needle made of plastic materials, such as polyethylene, polypropylene, polycarbonate, polyetheretherketone, etc. By adding auxiliary materials to the main material, the properties of the plastic are changed to make it suitable for electrostatic inkjet printing, such as adding graphite to give the plastic conductivity; a multi-material needle obtained by combining different parts of needles made of metal, non-metallic, ceramic, and plastic materials; and a tubular structure made of metal, non-metallic, ceramic, and plastic materials, such as a capillary tube, tapered tube, etc.

[0062] The pipette tip 5 is electrically connected to a power supply, which is a high-voltage power supply with high internal resistance. It uses a voltage doubler rectifier circuit to provide a controllable high voltage, and a high-value resistor is connected in series. The output internal resistance of the power supply is greater than or equal to 20MΩ, and the output voltage is 0.5kV-5kV.

[0063] Furthermore, the power supply is electrically connected to a controller, which specifically includes a host computer 61 (the main control terminal, such as a computer) and a slave computer 62 (such as a PLC controller). The host computer 61 is used to control the entire micro-liquid transfer system, and the slave computer 62 is used to control the specific power switch, X-axis motor 22, Y-axis motor 32, and Z-axis motor 43.

[0064] Furthermore, such as Figure 3 and Figure 4 As shown, the pipette tip 5 is specifically a slotted steel needle 51 with a diameter ranging from 200 μm to 2 mm, specifically 2 mm; the needle tip angle ranges from 10° to 60°, specifically 20°; and the tip end face has an area of ​​40,000 μm. 2 -4mm 2 The platform 53 is a polygon or circle, specifically a square with a side length of 100 μm; the needle tip has a slit 52 with a width ranging from 1 μm to 500 μm, specifically 50 μm wide. Although the slit steel needle 51 is more expensive, it can be used in continuous mass printing operations, with a total printable volume in the range of 100 nL to 1 μL.

[0065] Furthermore, in other embodiments, the pipette tip 5 can also be a solid steel needle with a diameter ranging from 200 μm to 2 mm; a needle tip angle ranging from 10° to 60°; and a tip end face with an area of ​​1 μm². 2 -1mm 2A polygonal or circular platform 53. Solid steel needles are relatively inexpensive and can meet most routine micropipette applications, allowing for printing of total volumes not exceeding 10 nL and enabling pipetting at the 100 pL level.

[0066] Furthermore, in other embodiments, the pipette tip 5 can also be a steel capillary with an outer diameter of 2μm-2mm and an inner diameter of 1μm-1mm. Steel capillary tips are mass-produced and disposable, completely avoiding sample contamination. Specifically, the pipette tip 5 can also be a conductive capillary glass tube with an outer diameter of 2μm-2mm and an inner diameter of 1μm-1mm. The surface of the capillary glass tube is coated with a conductive layer, such as gold, silver, or copper. Conductive capillary glass tubes have better hydrophilic / hydrophobic properties than steel capillary tips, resulting in higher sampling stability.

[0067] Furthermore, the mounting platform 23 is equipped with a liquid reservoir 24 and a receiver 25. The liquid reservoir 24 is specifically a perforated plate used to hold the liquid to be printed. The liquid to be printed can be a conductive liquid or a non-conductive or weakly conductive liquid. The micro-liquid transfer system of this invention is compatible with water-based solvents, organic solvents, or mixed solvents in the printing method. Water-based solvents include pure water and water with added solutes to change its physicochemical properties, such as conductivity (ionic salts, e.g., sodium chloride), viscosity (thickeners, e.g., dextran), volatility (humectants, e.g., glycerin), melting point (antifreeze agents, e.g., ethylene glycol), and surface tension (surfactants, e.g., Tween). Organic solvents include at least one of commonly used organic solvents such as dimethyl sulfoxide, acetonitrile, ethylene glycol, propylene glycol, dimethylacetamide, and N-methylpyrrolidone, and the physicochemical properties of the solvent can be changed by adding solutes in the same way as water-based solvents. Mixed solvents include any two or more of the above-mentioned solvents.

[0068] Examples include dimethyl sulfoxide (DMSO), acetonitrile, ethylene glycol, propylene glycol, dimethylacetamide, and N-methylpyrrolidone.

[0069] Furthermore, the receiver 25 is specifically a glass slide with a conductive coating on its surface or a perforated plate made of conductive plastic. The size of the glass slide is not limited, but it can be 25mm × 75mm. The conductive coating is not limited, but it can be a gold plating layer, a silver plating layer, or a copper plating layer. The glass slides can be repeatedly placed along the X-axis and Y-axis directions according to actual needs, and the number of slides can be 15 to 100.

[0070] Furthermore, receiver 25 is connected to a ground wire. When pipette 5 picks up liquid from reservoir 24, the controller energizes pipette 5. At this time, a potential difference is generated between pipette 5 and receiver 25, and the liquid adhering to the surface of pipette 5 is accurately sprayed onto receiver 25 under the action of the electric field. When pipette 5 is energized, the voltage difference between pipette 5 and receiver 25 is 0.5kV-5kV. In addition, the power supply is also connected to a capacitance measuring device, which can measure the capacitance between pipette 5 and reservoir 24, and between pipette 5 and receiver 25. By measuring the above capacitance values, non-contact or contact distance measurement and electrical characteristic measurement can be performed.

[0071] Furthermore, a cleaning tank or an automatic replacement device can be installed on the mounting platform 23. For reusable pipette tips 5, the cleaning tank includes a water tank, an ultrasonic cleaning device, and an automatic drying device. The pipette tips 5 are cleaned and dried in the cleaning tank, and the cleaning process is simple and does not easily generate contamination. For disposable pipette tips 5, an automatic replacement device can be installed to automatically replace the pipette tips 5, improving work efficiency.

[0072] Furthermore, a top-down distance sensor 71 is provided on the Z-axis worktable 41, and a bottom-up distance sensor 72 is provided on the mounting platform 23. Both the top-down distance sensor 71 and the bottom-up distance sensor 72 are reflective optical distance sensors. Of course, in other embodiments, contact distance sensors, ultrasonic distance sensors, confocal optical distance sensors, interferometric optical distance sensors, and time-of-flight optical distance sensors can also be selected.

[0073] The bottom-up distance sensor 72 can move synchronously with the mounting platform 23 and can measure the position error of the pipette head 5; the top-down distance sensor 71 can measure the position of the mounting platform 23, the position and error of all components on the mounting platform 23 (receiver 25, liquid reservoir 24) and the liquid level in the liquid reservoir 24. The accuracy of liquid transfer can be ensured by the bottom-up distance sensor 72 and the top-down distance sensor 71.

[0074] Furthermore, an optical imaging system 73 is installed on the Z-axis stage 41, which specifically includes an illumination source and a camera. Its illumination principle can be based on coaxial illumination, backlighting, or ring light illumination, and it is compatible with both bright-field and dark-field imaging. The working light wavelength can employ visible light imaging, invisible light imaging, or fluorescence imaging, and the device can quickly switch between different imaging modes by individually replacing the imaging system. The optical imaging system 73 has the function of accurately quantifying the volume and concentration of liquid being pipetted. Through the optical imaging system 73, the droplets formed by liquid pipetting on the receiver 25 can be photographed for quality control, ensuring that the position and volume of the droplets meet the requirements.

[0075] Furthermore, the micro-liquid transfer system also includes an environmental control component, which includes a closed container. The closed container can be a box or a shell to house the work platform 1 and all components on the work platform 1. The closed container can withstand a positive pressure of 50 Pa when locked.

[0076] The sealed container is equipped with a temperature control system, a humidity control system, a dust removal system, a gas internal circulation system, and a gas filling system. The temperature control system includes a refrigeration system and a heating system to maintain a constant temperature inside the sealed container. An additional high-precision temperature control device is mounted on the five-pipette array. The humidity control system consists of a humidification system and a dehumidification system, capable of controlling relative humidity from 5% to 100%. The dust removal system filters the gas inside the sealed container using a filter cartridge in an internal circulation manner to achieve a cleanliness level of 100,000. The gas internal circulation system allows the gas inside the sealed container to circulate continuously. The gas filling system can rapidly fill and displace the air inside the sealed container through an additional gas supply, such as inert gases like nitrogen or argon, or gases with special electrical properties like sulfur hexafluoride.

[0077] Example 2

[0078] This embodiment describes a method for transferring micro-liquids, using the micro-liquid transfer system described in Embodiment 1, such as... Figure 5 As shown, the specific steps include the following:

[0079] Step 1: System initialization.

[0080] Specifically, the motor is powered on and its position is initialized to zero for absolute position calibration. The host computer 61 transmits the pipetting position information to the slave computer 62, including the sampling position (i.e., the position of the reservoir 24) and the pipetting target position (i.e., the position of the receiver 25). During this step, the power supply is off, meaning the pipetting head 5 is de-energized.

[0081] Step 2, take the liquid.

[0082] Specifically, the lower-level machine 62 controls the X-axis motor 22 and Y-axis motor 32 to start, causing the liquid reservoir 24 to move below the pipette head 5. The lower-level machine 62 then controls the Z-axis motor 43 to start, causing the pipette head 5 to slowly descend until its tip is immersed in the liquid reservoir 24 to pick up the liquid. During this process, the lower-level machine 62 can determine whether the pipette head 5 is in contact with the liquid by detecting the capacitance value. It can control the pipette head 5 to be immersed to a specific height below the liquid surface using this method. Alternatively, the lower-level machine 62 can control the pipette head 5 to descend directly to a preset height, immersing its tip in the liquid.

[0083] Step 3, pipetting.

[0084] Specifically, the pipetting steps are as follows:

[0085] (1) The lower computer 62 controls the Z-axis motor 43 to raise the liquid-soaked pipette head 5 to a certain preset height higher than the printing target.

[0086] (2) The Y-axis motor 32 drives the receiver 25 to move slowly to the preset position.

[0087] (3) Depending on the actual situation, the receiver 25 is moved away from the pipette head 5 by the X-axis motor 22 to ensure that the moving speed of the receiver 25 reaches the expected uniform speed in subsequent steps. This step can be performed synchronously with step (2).

[0088] (4) Turn on the power supply and wait for the voltage to reach the preset voltage value.

[0089] (5) The X-axis motor 22 drives the mounting platform 23 to accelerate and move, so that the receiver 25 moves closer to the pipette head 5, and ensures that when the first pipette head 5 is close to the position above the receiver 25, the moving speed of the receiver 25 has reached the preset uniform speed.

[0090] (6) The lower-level machine 62 controls the opening and closing of the high-voltage switch, generates a high-voltage pulse on each independent pipette head 5, causes the pipette head 5 to spray droplets to spray the liquid onto the receiver 25, and realizes inkjet micro-pipette.

[0091] Each receiver 25 triggers a pulse at the corresponding position when it moves past a pipette tip 5, resulting in liquid ejection. Due to the position settings of the receiver 25, only a specific pipette tip 5 may eject ink in a single stroke, but each pipette tip 5 in the corresponding row will eject ink N times in succession, where N is the number of receivers 25 in a row.

[0092] (7) After the X-axis motor 22 moves to the point where all pipette tips 5 have swept past the receiver 25, it begins to decelerate.

[0093] (8) Move the Y-axis motor 32 according to the preset position.

[0094] (9) Repeat steps (6) and (7) to make the pipette head 5, which did not spray ink in step (6), spray ink at the corresponding preset position.

[0095] (10) Repeat steps (8) and (9) until all pipette tips 5 have been inkjet-ed onto this row of receivers 25.

[0096] (11) Repeat steps (6)-(10) for each row of receiver 25.

[0097] Step 4: Repeat steps 2 and 3 until all samples requiring pipetting have been pipetted.

[0098] Furthermore, in the method requiring cleaning or replacement of the pipette tip 5, after step 1, the lower-level machine 62 controls the X-axis motor 22, Y-axis motor 32, and Z-axis motor 43 to move the pipette tip 5 above the cleaning tank or disposable tip replacement area. The pipette tip 5 is cleaned by the automated cleaning tank fluid system or replaced with a new disposable pipette tip consumable by an automated mechanical structure. After cleaning or replacement is completed, step 2 is then performed.

[0099] Example 3

[0100] This embodiment discloses a micro-liquid transfer method using a micro-liquid transfer system. The micro-liquid transfer system differs from that in Embodiment 1 in that the mounting platform is fixedly mounted on the working platform, the liquid reservoir and receiver are mounted on the mounting platform, the X-axis worktable is mounted on the working platform, the Y-axis worktable is mounted on the X-axis worktable, the X-axis motor is used to drive the Y-axis worktable to move in the X-axis direction, the Z-axis worktable is mounted on the Y-axis worktable, the Y-axis motor is used to drive the Z-axis worktable to move in the Y-axis direction, the Z-axis worktable is provided with a Z-axis moving stage, and the Z-axis moving stage is provided with pipette heads distributed in an array.

[0101] The specific steps of the micro-liquid transfer method are as follows:

[0102] Step 1: System initialization.

[0103] Specifically, the motor is powered on and its position is reset to zero for absolute position calibration. The host computer transmits the pipetting position information to the slave computer, including the sampling position (i.e., the position of the reservoir 24) and the pipetting target position (i.e., the receiver position). During this step, the power is off, meaning the pipetting head 5 is de-energized.

[0104] Step 2, take the liquid.

[0105] Specifically, the lower-level computer controls the X-axis and Y-axis motors to move the pipette tip above the reservoir. The lower-level computer also controls the Z-axis motor to slowly lower the pipette tip, immersing its tip in the reservoir to pick up the liquid.

[0106] Step 3, pipetting.

[0107] Specifically, the pipetting steps are as follows:

[0108] (1) The lower computer controls the Z-axis motor to raise the pipette head dipped in liquid to a certain preset height higher than the printing target.

[0109] (2) Move the pipette head to the preset receiver position using the Y-axis motor.

[0110] (3) Depending on the actual situation, move the pipette tip away from the receiver using the X-axis motor to ensure that the moving speed of the pipette tip reaches the expected uniform speed in subsequent steps. This step can be performed synchronously with step (2).

[0111] (4) Turn on the power supply and wait for the voltage to reach the preset voltage value.

[0112] (5) The X-axis motor drives the pipette head to accelerate towards the receiver, and ensures that when the first pipette head is close to the position above the receiver, the pipette head moving speed has reached the preset uniform speed.

[0113] (6) The lower-level computer controls the opening and closing of the high-voltage switch to generate a high-voltage pulse on each independent pipette head, so that the pipette head sprays droplets to spray the liquid onto the receiver, thereby realizing inkjet micro-pipette.

[0114] Each time a pipette tip moves past a receiver, it triggers a pulse at the corresponding position to eject liquid. Depending on the receiver position settings, only a specific pipette tip may eject ink in a single stroke, but each pipette tip 5 in a corresponding row will eject ink N times sequentially, where N is the number of receivers 25 in a row.

[0115] (7) After the X-axis motor has moved to the point where all pipette tips have swept over the receiver, it begins to decelerate.

[0116] (8) Move the Y-axis motor according to the preset position.

[0117] (9) Repeat steps (6) and (7) to make the pipette that did not spray ink in step (6) spray ink at the corresponding preset position.

[0118] (10) Repeat steps (8) and (9) until all pipette tips 5 have been inkjet-ed onto this row of receivers 25.

[0119] (11) Repeat steps (6)-(10) for each row of receiver 25.

[0120] It will be apparent to those skilled in the art that this disclosure is not limited to the details of the exemplary embodiments described above, and that this disclosure can be implemented in other specific forms without departing from the spirit or essential characteristics of this disclosure. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of this disclosure is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within this disclosure.

[0121] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A micro-liquid transfer system, characterized by, The micro-volume liquid transfer system includes: A liquid storage container is used to store liquids to be transferred. A pipette tip, made of conductive material, is used to pick up and transfer liquid from a reservoir. A receiver, made of a conductive material, is used to receive liquid transferred by a pipette tip; A power supply, electrically connected to the pipette tip, is used to energize the pipette tip and create a voltage difference between the pipette tip and the receiver. The controller, electrically connected to the power supply, is used to control the power supply to or from the pipette tip. A drive assembly for driving the movement of a pipette tip, or for driving the movement of at least two of a reservoir, a pipette tip, and a receiver.

2. The micro-liquid transfer system according to claim 1, characterized in that, The pipette head is a solid or slit needle made of metal, a solid or slit needle made of non-metallic materials, a solid or slit needle made of ceramic materials, a solid or slit needle made of plastic materials, or a multi-material needle made by combining different parts of needles made of metal, non-metallic materials, ceramic materials, and plastic materials, or a tubular structure made of metal, non-metallic materials, ceramic materials, and plastic materials.

3. The micro-liquid transfer system according to claim 2, characterized in that, The solid needle has a diameter of 200μm-2mm, a needle tip angle of 10°-60°, and a tip end face that is a plateau with a diameter of 1μm-1000μm; and / or, The slit needle has a diameter of 200μm-2mm, a needle tip angle of 10°-60°, and a platform with a diameter of 1μm-1000μm at the tip. A slit with a width of 1μm-500μm is provided at the needle tip; and / or, The tubular structure has an outer diameter of 2μm-2mm and an inner diameter of 1μm-1mm.

4. The micro-liquid transfer system according to claim 1, characterized in that, The pipette head is provided in several parts, and the pipette heads are arranged in an array.

5. The micro-liquid transfer system according to claim 1, characterized in that, The micro-liquid transfer system also includes a working platform. The drive assembly includes a Z-axis worktable and a Z-axis moving stage mounted on the Z-axis worktable. The Z-axis worktable is equipped with a Z-axis motor for driving the Z-axis moving stage to rise and fall. The pipetting head is mounted on the Z-axis moving stage.

6. The micro-liquid transfer system according to claim 5, characterized in that, The work platform is also equipped with an X-axis worktable and a Y-axis worktable. An X-axis motor is installed on the X-axis worktable, and a Y-axis motor is installed on the Y-axis worktable. Wherein, the Y-axis worktable is mounted on the X-axis worktable, the X-axis motor drives the Y-axis worktable to move, a mounting platform is provided on the Y-axis worktable, the Y-axis motor drives the mounting platform to move, and the liquid reservoir and receiver are mounted on the mounting platform; or The X-axis worktable is mounted on the Y-axis worktable, the Y-axis motor is used to drive the X-axis worktable to move, the X-axis worktable is provided with a mounting platform, the X-axis motor is used to drive the mounting platform to move, and the liquid reservoir and receiver are mounted on the mounting platform.

7. The micro-liquid transfer system according to claim 6, characterized in that, The micro-liquid transfer system also includes a measurement component, which includes a bottom-up distance sensor and a top-down distance sensor; The bottom-up distance sensor is mounted on the mounting platform and is used to measure the position error of the pipette tip. The top-down distance sensor is mounted on the Z-axis worktable and is used to measure the position of the mounting platform, the position and error of all components on the mounting platform, and the liquid level in the liquid reservoir.

8. The micro-liquid transfer system according to claim 7, characterized in that, The bottom-up distance sensor and the top-down distance sensor are selected from contact distance sensors, ultrasonic distance sensors, reflective optical distance sensors, confocal optical distance sensors, interferometric optical distance sensors, and time-of-flight optical distance sensors.

9. The micro-liquid transfer system according to claim 5, characterized in that, The micro-liquid transfer system also includes an optical imaging system mounted on the Z-axis stage, which includes at least an illumination source and a camera.

10. The micro-liquid transfer system according to claim 1, characterized in that, The micro-liquid transfer system also includes a capacitance measuring device connected to a power source, which is used to measure the capacitance between the pipette tip and the reservoir, and between the pipette tip and the receiver.

11. The micro-liquid transfer system according to claim 1, characterized in that, The micro-liquid transfer system also includes an environmental control component, which includes a closed container and a temperature control system, a humidity control system, a dust removal system, a gas circulation system, and a gas injection system connected to the closed container. The enclosed container is used to house at least the reservoir, pipette tip, receiver, and drive assembly.

12. A method for transferring trace amounts of liquid, characterized in that, The micro-liquid transfer method uses the micro-liquid transfer system as described in claim 1, and specifically includes the following steps: Use the drive assembly to move the pipette tip, or move at least two of the reservoir, pipette tip, and receiver, so that the pipette tip picks up the liquid in the reservoir; Bring the pipette tip and receiver close to each other; Powering the pipette tip creates a voltage difference between it and the receiver, causing the liquid on the pipette tip to be sprayed onto the receiver, thus completing the liquid transfer.

13. The micro-liquid transfer method according to claim 12, characterized in that, The voltage difference between the pipette tip and the receiver is 0.5kV-5kV.

14. The method for transferring trace amounts of liquid according to claim 12, characterized in that, The output voltage of the power supply is 0.5kV-5kV; The receiver is connected to a ground wire.

15. The application of a micro-liquid transfer system as described in claim 1 or a micro-liquid transfer method as described in claim 12 in the printing of biological sample microarrays.

16. The application according to claim 15, characterized in that, The printing solvent is at least one of water-based solvent, organic solvent, or a mixture of water-based solvent and organic solvent.

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