Application method and device of Tip pipetting in high-altitude environment and storage medium

Abstract

The invention discloses an application method and device of Tip pipetting in a high-altitude environment and a storage medium. The application method comprises the following steps: 1, determining liquid suction and injection compensation amounts; 2, the liquid suction and injection pressure compensation amount is determined; 3, liquid level detection operation; 4, liquid suction operation; and 5, liquid injection operation. According to the method, an influence equation of liquid filling when the altitude changes is obtained according to liquid characteristics and in combination with an influence rule during Tip pipetting, and liquid suction and injection parameters are automatically corrected according to the altitude in a software linkage mode. By means of the mode, the instrument achieves automatic correction when used in the high altitude area, manpower is saved, cost is reduced, and adverse effects caused by personnel differences are avoided. After compensation is conducted through the method, the liquid injection amount is obviously increased, the attenuation compensation effect is obvious, and the consistency and repeatability of the liquid injection amount are obviously improved.

Description

Technical Field

[0001] The present invention relates to the field of in vitro diagnosis, and particularly to an application method, device and storage medium of Tip pipetting in a high-altitude environment. Background Art

[0002] The Tip head sampling system generally consists of a plunger pump composed of a plunger, a plunger rod and a pump chamber, cooperating with a disposable Tip head (pipette tip), to achieve precise inhalation and discharge of trace amounts of liquid. Its working principle is the air displacement principle, and it is widely used in in vitro diagnostic instruments.

[0003] When the Tip head sampling system is working, when the external atmospheric pressure changes, the inhalation and discharge of the liquid will be significantly affected. In addition, the self-properties of the liquid, such as density, viscosity, surface tension, contact angle, etc., are also affected by the external environment; as the altitude increases, the atmospheric pressure and temperature decrease, the liquid density increases slightly, and usually the liquid is regarded as an incompressible fluid, so the slight change in density is often ignored, but the viscosity is sensitive to temperature and altitude, and the liquid viscosity increases when the altitude increases. In addition, when the altitude increases and the temperature decreases, the liquid surface tension increases, which will directly affect the process of the liquid detaching from the Tip head, and at the same time the contact angle is also affected by the change in surface tension, which will directly affect the inhalation and discharge of the liquid during the precise pipetting operation of the Tip head sampling system. At present, to solve the above problems, usually the method of re-adjusting locally is adopted to correct the liquid suction and injection, which makes the operation cumbersome, the workload large, the time-consuming long, the cost high, and the correction effect is greatly affected by the operator's operation level. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide an application method of Tip pipetting in a high-altitude environment. Another purpose of the present invention is to provide a device for implementing this method. Still another purpose of the present invention is to provide a storage medium for storing a computer program to execute each step of this method, so as to achieve precise liquid suction, pipetting and injection of the Tip sampling system in a high-altitude environment.

[0005] To achieve the above purposes, the present invention adopts the following technical solutions: The application method of Tip pipetting in a high-altitude environment according to the present invention includes the following steps: Step 1, determining the liquid suction and injection compensation amounts: Step 1.1, according to the altitude of the working place of the pipetting device, calculating the liquid property influence factors of the liquid to be aspirated and injected at this altitude, and according to the air volume of the pipetting device and the set liquid suction and injection volume x1, calculating the theoretical liquid suction and injection volume y1 at this altitude through the filling equation; The filling equation is preferably: y1 = ax1 α + bx2 β+cx3 γ +dx4 δ +k; In the formula: x1—Set the liquid suction and injection volume; x2—The air volume of the pipetting device, including the sum of the pump chamber volume, adapter volume and Tip head volume. If there is a pipeline connection in the system, it also includes the pipeline volume; x3—Altitude; x4—Equivalent of liquid characteristics; a—Influence coefficient of filling volume; b—Influence coefficient of system air volume; c—Influence coefficient of altitude; d—Influence factor of liquid characteristics; α—Influence index of filling volume; β—Influence index of system air volume; γ—Influence index of altitude; δ—Influence index of liquid characteristics; k—Constant; Step 1.2, retrieve the altitude of the factory commissioning location of the pipetting device, calculate the liquid characteristic influence factor at the altitude of the factory commissioning location, and calculate the theoretical liquid suction and injection volume y2 at the altitude of the factory commissioning location through the filling equation according to the air volume of the pipetting device and the set liquid suction and injection volume x1. Take the difference between the two theoretical liquid suction and injection volumes y1 and y2, and the liquid compensation volume Δy = y2 - y1 required by the pipetting device at the working location can be obtained; Step 2, determine the liquid suction and injection pressure compensation volume: Collect the atmospheric pressure several times at the working location of the pipetting device, take the average value to obtain the pressure reference value, calculate the pressure difference between the working location and the factory commissioning location of the pipetting device through the formula, normalize the pressure reference value, and perform the same calculation and adjustment on each subsequent collected pressure value to obtain the pressure equivalent; Set the liquid level detection threshold, air suction threshold, needle blockage threshold, missing addition threshold and dripping threshold at the altitude of the working location of the pipetting device; The preferred formula for calculating the pressure difference between the working location and the factory commissioning location of the pipetting device is P = λH m +n+P0; In the formula: P—Pressure AD value; H—Altitude; λ—Influence coefficient of altitude; m—Influence index of altitude; n—Constant; P0—Pressure AD value of the factory commissioning location of the pipetting device; Pressure AD value: The analog electrical signal value collected by the pressure sensor is converted into a digital electrical signal value, which is a dimensionless quantity; Step 3, liquid level detection operation: The instrument moves the pipetting device to the liquid suction position and then moves downward. At the same time, the plunger moves downward from the maximum stroke position. The pressure sensor continuously detects the pressure value in the pump chamber and compares it with the corrected liquid level detection threshold: If the pressure value in the pump chamber detected by the pressure sensor does not reach the liquid level detection threshold within the set time, it is determined that the liquid volume in the sample tube is insufficient, and the operator is prompted to supplement the liquid. When the pressure value in the pump chamber detected by the pressure sensor reaches the liquid level detection threshold within the set time, it is determined that this is the liquid level position, and Step 4 is executed; Step 4, liquid suction operation: After obtaining the liquid level position, the instrument lowers the Tip head of the pipetting device to the liquid suction position to perform the liquid suction step; the liquid suction position refers to the liquid position at a certain depth increased on the basis of the position where the Tip head detects the liquid level; Call the liquid suction parameters with the compensation amount Δy = y2 - y1 added. The plunger moves up the corresponding stroke according to the compensated liquid suction volume to suck the liquid. During the liquid suction process, the pressure sensor continuously detects the pressure value in the pump chamber and compares it with the corrected air suction threshold and needle clogging threshold: If the air suction threshold or the needle clogging threshold is reached, the pipetting device performs the liquid suction process 1 or more times again. If the air suction threshold or the needle clogging threshold is still reached after the repeated liquid suction process exceeds the set time, it is determined that the liquid suction fails, and this test is marked as skipped or the operator is prompted to perform manual intervention, replace the Tip head or process the liquid. If the liquid suction process does not reach the air suction threshold or the needle clogging threshold, the liquid suction process ends, and Step 5 is executed; Step 5, liquid injection operation: After the liquid suction is completed, the instrument moves the pipetting device to the liquid injection position, calls the compensated liquid injection parameters, and the plunger moves down the corresponding stroke according to the compensated liquid injection volume to inject the liquid into the reaction vessel. During the liquid injection process, the pressure sensor continuously detects the pressure value in the pump chamber and compares it with the corrected liquid omission threshold. If the liquid omission threshold is reached, it is determined that the liquid has not been successfully injected into the reaction vessel, and this test is marked as skipped or the operator is prompted to perform manual intervention, replace the Tip head or process the liquid, and repeat Step 4. If the liquid injection does not reach the liquid omission threshold, it is determined that the liquid has been successfully discharged, and the liquid injection process ends.

[0006] Further, in step 5, when the instrument moves the pipetting device to the liquid injection level, the pressure sensor continuously detects the pressure value in the pump chamber and compares it with the corrected dripping threshold. If the dripping threshold is reached, it is determined that liquid dripping occurs during the process of the instrument moving the pipetting device to the liquid injection level, and liquid compensation is required during liquid injection; if the dripping threshold is not reached, it is determined that no liquid dripping occurs, and the subsequent liquid injection process is normally executed.

[0007] According to the liquid characteristics of the present invention, combined with the influence law during Tip pipetting, the influence equation of liquid filling with the change of altitude is obtained. Through software linkage, the liquid suction and injection parameters are automatically corrected according to the altitude. In this way, the instrument realizes automatic calibration when used in high-altitude areas, saves manpower, reduces costs, and avoids the adverse effects brought by personnel differences.

[0008] The liquid injection effect after compensation by the method of the present invention is as Figure 5 shown; Figure 5 It can be seen that before compensation by the method of the present invention, as the altitude increases, the liquid injection volume gradually decreases, and the larger the liquid volume, the greater the attenuation. After compensation by the method of the present invention, the liquid injection volume is significantly increased, the compensation effect of attenuation is significant, and the consistency and repeatability of the liquid injection volume are also significantly improved.

[0009] The present invention corrects the pressure value, pressure difference value and threshold according to the altitude, improves the accuracy of abnormal alarm, brings a positive impact on the customer experience and instrument use, and the effect after correcting the pressure value is as Figure 6 shown; Figure 6 The suction pressure difference in Figure 6 is equal to the difference between the reference value and the peak pressure during the suction process. It can be seen from Attached Drawing Explanation

[0010] Figure 1 is the flow chart of the application method described in the present invention.

[0011] Figure 2 is the flow chart for calculating the suction and injection compensation amounts described in the present invention.

[0012] Figure 3 is the flow chart for calculating the suction and injection pressure compensation amounts described in the present invention.

[0013] Figure 4 is the schematic structural diagram of the pipetting device described in the present invention.

[0014] Figure 5It is a curve comparison diagram before and after the compensation of the suction and injection liquid volume described in the present invention.

[0015] Figure 6 It is a curve comparison diagram before and after the compensation of the suction and injection liquid pressure described in the present invention. Detailed implementation manners

[0016] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings. These embodiments are implemented on the premise of the technical solution of the present invention, and detailed implementation manners and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0017] In the description of the present invention, unless otherwise clearly defined and limited, the terms "connected" and "connected" that may appear should be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection or an electrical connection; it may be a direct connection or an indirect connection through an intermediate medium, and it may be the communication inside two components. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood through specific situations.

[0018] The application method of the Tip pipetting described in the present invention in a high-altitude environment adopts the following pipetting device: As Figure 4 shown, it includes a motor drive mechanism 1, a piston pump 2, an adapter 3, a Tip head 4, and a pressure sensor 5.

[0019] The control signal input end of the motor drive mechanism 1 is connected to the control signal output end of the upper computer, and the power output end of the motor drive mechanism 1 is connected to the power input end of the piston pump 2; the liquid inlet and outlet of the piston pump 2 are connected to the Tip head 4 through the adapter 3, and the detection port of the pressure sensor 5 is connected to the pump chamber 2.1 of the piston pump 2, which is used to detect the pressure value in the pump chamber 2.1 in real time during the liquid suction and injection process of the piston pump 2, and output the pressure value to the upper computer.

[0020] The working process of the pipetting device is as follows: 1. Liquid suction: The motor drive mechanism 1 controls the piston 2.2 of the piston pump 2 to move upward, the pressure in the pump chamber 2.1 is less than the external atmospheric pressure, and the sample liquid enters the pump chamber 2.1 through the adapter 3 and the Tip head 4 under the action of the external atmospheric pressure to complete the liquid suction.

[0021] 2. Liquid injection: The motor drive mechanism 1 controls the piston 2.2 of the piston pump 2 to move downward, the volume of the pump chamber 2.1 is compressed, and the sample liquid flows out from the Tip head 3 under the action of the pressure in the pump chamber 2.1 to achieve liquid injection.

[0022] 3. The pressure sensor 5 detects the pressure changes in the pump chamber 2.1 during the processes of liquid extraction, liquid injection, and liquid transfer in real time, and sends the detected pressure value to the host computer. The host computer records the detected pressure value and executes the steps of liquid suction, liquid injection, and liquid transfer according to the detected pressure value.

[0023] The storage medium provided by the present invention stores a computer program for controlling the steps of liquid suction, liquid injection, and liquid transfer by the host computer processor.

[0024] It can be understood that if the method in this embodiment is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on such an understanding, the essence of the technical solution of this application, or the part that contributes to the prior art, or all or part of this technical solution can be embodied in the form of a software product. This computer software product is stored in a storage medium and executes all or part of the steps of this embodiment. The storage medium includes various media that can store program codes such as USB flash drives, mobile hard disks, read-only memories (ROMs), random access memories (RAMs), magnetic disks, or optical discs.

[0025] As Figures 1-4 shown, the application method of the Tip liquid transfer of the present invention in a high-altitude environment is carried out according to the following steps: Step 1, determine the liquid suction and injection compensation amounts: Step 1.1, according to the altitude of the working place of the liquid transfer device, calculate the liquid property influence factor of the liquid to be sucked and injected at this altitude, and calculate the theoretical liquid suction and injection amounts y1 at this altitude through the filling equation according to the air volume of the liquid transfer device and the set liquid suction and injection amounts x1; y1 = ax1 α + bx2 β + cx3 γ + dx4 δ + k; In the formula: x1 - the set liquid suction and injection amounts; x2 - the air volume of the liquid transfer device, including the sum of the pump chamber volume, adapter volume, and Tip head volume. If there is a pipeline connection in the system, it also includes the pipeline volume; x3 - the altitude; x4 - the liquid property equivalent; a - the filling amount influence coefficient; b - the system air volume influence coefficient; c - the altitude influence coefficient; d - the liquid property influence factor; α—filling volume impact index; β—system air volume influence index; γ—altitude impact index; δ—Liquid property influence index; k—constant; The above coefficients and indices are called up based on the database established during the research process, combined with the air volume, liquid volume, and liquid characteristics of the device.

[0026] Step 1.2, retrieve the altitude of the factory debugging site of the pipetting device, calculate the liquid characteristic influencing factor at the factory debugging site altitude, and calculate the theoretical suction and injection volume y2 at the factory debugging site altitude according to the air volume of the pipetting device and the set suction and injection volume x1 through the filling equation, and the difference between the two theoretical suction and injection volumes y1 and y2 is obtained to obtain the liquid compensation amount Δy=y2-y1 required by the pipetting device at the working site; Step 2, determine the suction and injection pressure compensation amount: At the working place of the pipetting device, collect the atmospheric pressure several times, calculate the average value to get the pressure reference value, and use the formula P=λH m +n+P0, calculate the pressure difference between the working place of the pipetting device and the factory debugging place, normalize the pressure reference value, and make the same calculation and adjustment for each pressure value collected subsequently to obtain the pressure equivalent; set the liquid level detection threshold, empty suction threshold, needle blockage threshold, leakage threshold and dripping threshold at the altitude of the working place of the pipetting device.

[0027] Where: P—pressure AD value; H—altitude above sea level; λ—Altitude influence coefficient; m—altitude impact index; n—constant; P0—pressure AD value of the pipetting device at the factory commissioning site; Pressure AD value: The analog electrical signal value collected by the pressure sensor is converted into a digital electrical signal value, which is a dimensionless quantity; Step 3, liquid level detection operation: The instrument moves the liquid transfer device to the liquid suction position and then moves downward, while the plunger 2.2 moves downward from the maximum stroke position, and the pressure sensor 5 detects the pressure value in the pump chamber 2.1 in real time and compares it with the corrected liquid level detection threshold value: If the pressure value in the pump chamber 2.1 detected by the pressure sensor 5 does not reach the liquid level detection threshold within the set time, it is determined that the liquid in the sample tube is insufficient, and the operator is prompted to add liquid; when the pressure value in the pump chamber 2.1 detected by the pressure sensor 5 reaches the liquid level detection threshold within the set time, it is determined that this is the liquid level position, and step 4 is executed; Step 4, liquid suction operation: After obtaining the liquid level position, the instrument lowers the Tip head 4 of the pipetting device to the liquid suction position to perform the liquid suction step; the liquid suction position refers to the liquid position at a certain depth increased on the basis of the position where the Tip head detects the liquid level; Call the liquid suction parameters after adding the compensation amount Δy = y2 - y1, and the plunger 2.2 moves up the corresponding stroke according to the compensated liquid suction volume to suck the liquid; during the liquid suction process, the pressure sensor 5 continuously detects the pressure value in the pump chamber 2.1 and compares it with the corrected air suction threshold and needle clogging threshold: If the air suction threshold or the needle clogging threshold is reached, the plunger 2.2 returns to the minimum stroke position and then performs the liquid suction process one or more times. If the air suction threshold or the needle clogging threshold is still reached after the re-liquid suction process exceeds the set time, it is determined that the liquid suction fails, and this test is marked as skipped or the operator is prompted to replace the Tip head or make corresponding treatments; if the liquid suction process does not reach the air suction threshold or the needle clogging threshold, the liquid suction process ends and Step 5 is executed; Step 5, liquid injection operation: After the liquid suction is completed, the instrument moves the pipetting device to the liquid injection position, calls the compensated liquid injection parameters, and the plunger 2.2 moves down the corresponding stroke according to the compensated liquid injection volume to inject the liquid into the reaction vessel; during the liquid injection process, the pressure sensor 5 continuously detects the pressure value in the pump chamber and compares it with the corrected missing addition threshold. If the missing addition threshold is reached, it is determined that the liquid has not been successfully injected into the reaction vessel, and this test is marked as skipped or the operator is prompted to perform manual intervention, replace the Tip head or process the liquid, and repeat Step 4; if the liquid injection does not reach the missing addition threshold, it is determined that the liquid has been successfully discharged and the liquid injection process ends.

[0028] In Step 5, during the process of the instrument moving the pipetting device to the liquid injection position, the pressure sensor 5 continuously detects the pressure value in the pump chamber 2.1 and compares it with the corrected dripping threshold. If the dripping threshold is reached, it is determined that liquid drips occur during the process of the instrument moving the pipetting device to the liquid injection position, and liquid compensation is required during liquid injection; if the dripping threshold is not reached, it is determined that no liquid drips occur and the subsequent liquid injection process is normally executed.

[0029] Finally, it should be emphasized that the above description is only the preferred embodiment of the present invention and is not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, they can still make modifications to the technical solutions described in the foregoing embodiments without creative efforts, or make equivalent replacements for some of the technical features. Therefore, any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for applying Tip pipetting in a high altitude environment, characterized in that: The steps include: Step 1, determine the suction and injection compensation amount: Step 1.1, according to the altitude of the working place of the pipetting device, calculate the influencing factors of the liquid characteristics of the intended suction and injection at the altitude, and calculate the theoretical suction and injection volume y1 at the altitude through the filling equation according to the air volume of the pipetting device and the set suction and injection volume x1; Step 1.2, retrieve the altitude of the factory debugging site of the pipetting device, calculate the liquid characteristic influencing factor at the factory debugging site altitude, and calculate the theoretical suction and injection volume y2 at the factory debugging site altitude according to the air volume of the pipetting device and the set suction and injection volume x1 through the filling equation, and the difference between the two theoretical suction and injection volumes y1 and y2 is obtained to obtain the liquid compensation volume Δy=y2-y1 required by the pipetting device at the working site; Step 2, determine the suction and injection pressure compensation amount: Atmospheric pressure is collected several times at the working place of the pipetting device, and the average value is obtained to obtain the pressure reference value. The pressure difference between the working place of the pipetting device and the factory debugging place is calculated by a formula, the pressure reference value is normalized, and the same calculation and adjustment are performed on each pressure value collected subsequently to obtain the pressure equivalent; the liquid level detection threshold, empty suction threshold, needle blocking threshold, leakage threshold and dripping threshold are set at the altitude of the working place of the pipetting device; Step 3, liquid level detection operation: The instrument moves the pipetting device to the liquid aspiration position and then moves downward. At the same time, the pressure sensor detects the pressure value in the pipetting device in real time and compares it with the corrected liquid level detection threshold: If the pressure value detected by the pressure sensor does not reach the liquid level detection threshold within the set time, it is determined that the liquid in the sample tube is insufficient, and the operator is prompted to add liquid; when the pressure value detected by the pressure sensor reaches the liquid level detection threshold within the set time, it is determined that this is the liquid level position, and step 4 is executed; Step 4, liquid aspiration operation: After obtaining the liquid surface position, the instrument lowers the Tip head of the pipette device to the liquid aspiration position to perform the liquid aspiration step; calls the liquid aspiration parameter after adding the compensation amount Δy=y2-y1; the pipette device aspirates liquid according to the compensated liquid aspiration amount; during the liquid aspiration process, the pressure sensor detects the pressure value in the pipette device in real time and compares it with the corrected empty aspiration threshold and needle blocking threshold: If the empty suction threshold or the needle blocking threshold is reached, the pipette device re-executes the aspiration process. If the re-aspiration process exceeds the set time and still reaches the empty suction threshold or the needle blocking threshold, it is judged that the aspiration has failed, and the test is marked to be skipped or the operator is prompted to intervene manually, replace the tip head or process the liquid; if the aspiration process does not reach the empty suction threshold or the needle blocking threshold, the aspiration process ends and step 5 is executed; Step 5, injection operation: After the aspiration is completed, the instrument moves the pipetting device to the injection position, calls the compensated injection parameters, and the pipetting device injects the liquid into the reaction container according to the compensated injection volume; during the injection process, the pressure sensor detects the pressure value in the pipetting device in real time and compares it with the corrected leakage threshold. If the leakage threshold is reached, it is determined that the liquid has not been successfully injected into the reaction container, and the test is marked to be skipped or the operator is prompted to intervene manually, replace the Tip head or process the liquid, and repeat step 4; if the injection does not reach the leakage threshold, it is determined that the liquid is successfully discharged and the injection process is completed.

2. The application method of Tip pipetting in a high altitude environment according to claim 1, characterized in that: The filling equation is y1=ax1 α +bx2 β +cx3 γ +dx4 δ +k; Where: x1—Set the suction and injection volume; x2—air volume of the pipette, including the sum of the pump chamber volume, adapter volume and Tip head volume. If there is a pipeline connection in the system, it also includes the pipeline volume; x3—altitude above sea level; x4—liquid characteristic equivalent; a—influence coefficient of filling volume; b—system air volume influence coefficient; c—Altitude influence coefficient; d—fluid property influence factor; α—filling volume impact index; β—system air volume influence index; γ—altitude impact index; δ—Liquid property influence index; k—constant; The pressure difference between the working place of the pipetting device and the factory debugging place is calculated by P=λH m +n+P0; Where: P—pressure AD value; H—altitude above sea level; λ—Altitude influence coefficient; m—altitude impact index; n—constant; P0—pressure AD value of the pipetting device at the factory commissioning site; Pressure AD value: The analog electrical signal value collected by the pressure sensor is converted into a digital electrical signal value, which is a dimensionless quantity.

3. The application method of Tip pipetting in a high altitude environment according to claim 1, characterized in that: In step 5, when the instrument moves the pipetting device to the injection position, the pressure sensor detects the pressure value in the pipetting device in real time and compares it with the corrected dripping threshold. If the dripping threshold is reached, it is determined that liquid dripping occurs when the instrument moves the pipetting device to the injection position, and liquid compensation is required during injection; if the dripping threshold is not reached, it is determined that liquid dripping does not occur, and the subsequent injection process is performed normally.

4. A Tip pipetting device in a high altitude environment, applied to the application method of Tip pipetting in a high altitude environment according to any one of claims 1 to 3, characterized in that: The liquid transfer device comprises a motor drive mechanism, a plunger pump, an adapter, a tip head and a pressure sensor; The control signal input end of the motor drive mechanism is connected to the control signal output end of the host computer, and the power output end of the motor drive mechanism is connected to the power input end of the plunger pump; the liquid inlet and outlet of the plunger pump are connected to the Tip head through the adapter; the detection port of the pressure sensor is connected to the pump cavity of the plunger pump, and is used to detect the pressure value in the pump cavity during the liquid extraction process of the plunger pump in real time, and output the pressure value to the host computer.

5. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores a computer program, and when the computer program is executed by the processor, each step of the method for applying Tip pipetting in a high-altitude environment as claimed in any one of claims 1 to 3 is implemented.

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