Method for treating a volatile liquid and liquid treatment device

Abstract

A method for handling a volatile liquid using a pipette, comprising: a low-volatility liquid suction step of suctioning a low-volatility liquid having a lower volatility than the volatile liquid from a suction / discharge port; an air suction step of suctioning air from the suction / discharge port after the low-volatility liquid suction step; and a volatile liquid suction step of suctioning the volatile liquid from the suction / discharge port after the air suction step.

Description

TECHNICAL FIELD

[0001] The present application relates to a method for handling a volatile liquid using an air displacement piston pipette, and a liquid handling apparatus that performs the method. BACKGROUND

[0002] In physical and chemical experiments, an air displacement piston pipette is widely used in order to measure and dispense a liquid. The piston pipette has a structure in which air is introduced into and discharged from a cylinder by moving a piston up and down in the cylinder, and by adjusting the distance of moving the piston up and down, a liquid can be accurately measured in a tip attached to the front end of the cylinder.

[0003] A device for electrically operating a piston pipette is also sold by various companies, and this device can perform continuous suction and continuous discharge. As such an automatic dispensing device, there are Bravo by Agilent, NIMBUS by Affymetrix, epMotion by Eppendorf, Microlab by Hamilton, Biomak by Beckman Coulter, and the like.

[0004] The piston pipette is a structure in which a liquid is measured by introducing and discharging air, and thus, for a liquid such as water that has low volatility, accurate measurement can be performed, but for a liquid such as acetonitrile (ACN) and acetone that has high volatility, there is a problem in that after suction, liquid leakage easily occurs from the suction / discharge port, and accurate measurement is difficult. As a reason for this, it can be considered that when a liquid with high volatility is sucked from the suction / discharge port, the pressure in the cylinder of the pipette changes due to the vapor of the volatile liquid, or the temperature in the cylinder changes due to the heat of vaporization generated by evaporation, and thus, the air present in the cylinder expands, and the volatile liquid is squeezed out. This is also disclosed in Non-Patent Literature 1.

[0005] PRIOR ART DOCUMENTS

[0006] NON-PATENT LITERATURE

[0007] Non-Patent Literature 1: The 82nd Japan Society for Analytical Chemistry Organic Microanalysis Research Forum - The 98th Society of Instrument and Control Engineers Mechanics Quantity Measurement Department Joint Symposium (32nd Presentation Materials) Theme: About Dispensing Operation Using a Micro Pipette (Japanese: The 82nd Japan Society for Analytical Chemistry Organic Microanalysis Research Forum - The 98th Society of Instrument and Control Engineers Mechanics Quantity Measurement Department Joint Symposium (32nd Presentation Materials) Theme: About Dispensing Operation Using a Micro Pipette)

[0008] Non-Patent Literature 2: https: / / ocw.kyoto-u.ac.jp / ja / faculty-of-agriculture-jp / 5129000 / pdf / 03.pdf

[0009] Non-Patent Literature 3: https: / / www.aandd.co.jp / adhome / pdf / tech_doc / analytical / pipette_guide.pdf SUMMARY

[0010] Problem to be solved by the invention

[0011] As described above, in the case of handling a volatile liquid with a pipette or the like, the following phenomenon occurs: at the time of suction, the air layer in the tip, the barrel is expanded due to the volatilization of the liquid, the pressure rises, and the liquid is squeezed out. This phenomenon is called liquid leakage or droplet. As a result, accurate measurement of the liquid becomes impossible.

[0012] As a method for reducing the influence caused by volatilization of a volatile liquid, it has also been proposed to repeatedly perform suction and discharge of the liquid a plurality of times before measurement of the volatile liquid, and to saturate the air layer with volatilized liquid molecules (refer to Non-Patent Literatures 2 and 3). However, in the case of adopting this method, although it is possible to reduce the liquid leakage speed from the suction / discharge port, it is not possible to completely eliminate liquid leakage.

[0013] In addition, the above method intentionally volatilizes the liquid to be measured to saturate the air layer in the barrel, and therefore there is a problem that the amount of the liquid to be measured decreases due to evaporation. For example, if the amount of the liquid to be measured is 500 μL, even if 2 μL or so is volatilized to become 498 μL, the decrease amount is about 4%, which can be said to be a small influence. However, in the case where the amount of the liquid to be measured is only a small amount such as 5 μL, when 2 μL or so is volatilized out of 5 μL to become 3 μL, about 40% of the liquid is decreased, and the influence becomes very large.

[0014] Therefore, in particular, in the case of handling a volatile liquid in a small amount of several μL or so, the above method cannot be adopted.

[0015] Therefore, the purpose of the present application is to suppress liquid leakage from a pipette caused by volatilization of a volatile liquid.

[0016] Solution for solving the problem

[0017] The processing method of the present application is a processing method of a volatile liquid using a pipette having a cylinder, a piston sliding in the cylinder, and a tip having a suction / discharge port and attached to the front end of the cylinder, and sucking and discharging a liquid from the suction / discharge port of the tip in accordance with the operation of the piston. The processing method includes the following steps.

[0018] a low-volatility liquid suction step of sucking a low-volatility liquid having a lower volatility than the volatile liquid from the suction / discharge port after the low-volatility liquid suction step; and

[0019] an air suction step of sucking air from the suction / discharge port after the low-volatility liquid suction step; and

[0020] a volatile liquid suction step of sucking the volatile liquid from the suction / discharge port after the air suction step.

[0021] The liquid processing apparatus of the present application is an apparatus configured to execute the above processing method using a pipette, and includes: a pipette having a cylinder disposed in the vertical direction, a piston sliding in the cylinder in the vertical direction, and a tip having a suction / discharge port at the front end and attached to the lower end of the cylinder with the suction / discharge port facing downward, and sucking and discharging a liquid from the suction / discharge port of the tip in accordance with the operation of the piston; a drive mechanism for operating the pipette; a volatile liquid container containing a volatile liquid; a low-volatility liquid container containing a low-volatility liquid having a lower volatility than the volatile liquid; and a control section for controlling the drive mechanism. The control section is configured to control the drive mechanism to perform the following operations during the suction of the volatile liquid using the pipette: a low-volatility liquid suction operation of sucking a predetermined amount of the low-volatility liquid from the low-volatility liquid container; an air suction operation of sucking a predetermined amount of air from the suction / discharge port after the low-volatility liquid suction operation; and a volatile liquid suction operation of sucking a predetermined amount of the volatile liquid from the volatile liquid container after the air suction operation.

[0022] The low-volatility liquid in the present application refers to a substance having a boiling point of 95°C or higher and being in a liquid state at normal temperature (20°C ± 15°C). As such a low-volatility liquid, for example, water, dimethyl sulfoxide, glycerol, and phenol can be listed.

[0023] The volatile liquid in the present application refers to a substance having a boiling point in the range of 50 to 95°C and being in a liquid state at normal temperature (20°C ± 15°C), or a liquid containing such a substance at 10% or more. As the substance having a boiling point in the range of 50 to 95°C and being in a liquid state at normal temperature (20°C ± 15°C), there can be mentioned, for example, acetonitrile, methanol, ethanol, acetone, toluene, isopropanol, hexane, butanol, cyclohexane, ethylene glycol, benzene, chloroform, acetaldehyde, triethylamine, phenol, naphthalene, formaldehyde, tetrahydrofuran, ethyl acetate.

[0024] Effects of the invention

[0025] In the volatile liquid processing method of the present application, after performing suction of a low volatile liquid having lower volatility than the volatile liquid and air (hereinafter referred to as pre-suction), the volatile liquid is suctioned, and therefore, compared with the case where the pre-suction is not performed, the volume of the air layer present on the upper side of the volatile liquid suctioned into the pipette becomes small. Thereby, the expansion volume of the air layer expanded due to the volatilization of the volatile liquid becomes small, and therefore, compared with the case where the pre-suction is not performed, the occurrence of the leakage of the volatile liquid from the pipette becomes less likely, and the measurement accuracy of the volatile liquid is improved.

[0026] For the liquid processing apparatus of the present application, the control section that controls the driving mechanism for driving the pipette is configured in such a manner that, in the process of suctioning the volatile liquid with the pipette, the suction of the volatile liquid is performed after performing the above-described pre-suction, and therefore, the leakage of the volatile liquid from the pipette becomes less likely, and the measurement accuracy of the volatile liquid is improved. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 A diagram showing the outline configuration of one embodiment of the liquid processing apparatus.

[0028] Figure 2 A flowchart showing one example of a series of operations at the time of suction of a liquid in the embodiment.

[0029] Figure 3 A schematic view showing the state in the tip after suction of a liquid in the embodiment.

[0030] Figure 4 An image diagram for comparing the residual amount of a liquid in the tip in the case where the pre-suction is performed with the case where the pre-suction is not performed, (A) is the case where the pre-suction is performed, and (B) is the case where the pre-suction is not performed.

[0031] Figure 5 A graph showing the standard curve of a peptide obtained by continuous dilution with respect to the case where the pre-suction is performed and the case where the pre-suction is not performed.

[0032] Figure 6An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 2 μL.

[0033] Figure 7 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 3 μL.

[0034] Figure 8 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 5 μL.

[0035] Figure 9 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 10 μL.

[0036] Figure 10 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 50 μL.

[0037] Figure 11 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 100 μL.

[0038] Figure 12 An image of the liquid remaining amount in the tip in the case where pre-suction was performed with the air layer volume set to 150 μL. DETAILED DESCRIPTION

[0039] Hereinafter, an embodiment of the volatile liquid treatment method of the present application and a liquid treatment device that executes the treatment method will be described with reference to the drawings.

[0040] First, the liquid treatment device of the embodiment will be described with reference to FIG. 1. Figure 1 An embodiment of the liquid treatment device will be described.

[0041] In the liquid treatment device of the embodiment, a plurality of pipettes 2 are held by the holder 10 in a state of being aligned in a row. The pipette 2 is provided with a cylinder 4 arranged in the vertical direction, a piston 6 that slides in the vertical direction inside the cylinder 4, and a tip 8 attached to the lower end of the cylinder 4. The tip 8 has a suction / discharge port at the front end, and the suction / discharge port is vertically downward.

[0042] Each of the pipettes 2 sucks in and discharges a liquid, a gas from and to the suction / discharge portion of the tip 8 in conjunction with upward and downward operations of the piston 4. In addition, the pipette 2 moves in the horizontal plane direction and the vertical direction to suck in and discharge a liquid to and from a desired container. In this embodiment, all of the pipettes 2 are held by the common holder 10, and the holder 10 moves in the horizontal plane direction and the vertical direction, whereby each of the pipettes 2 moves in the horizontal plane direction and the vertical direction.

[0043] The drive mechanism 12 includes a mechanism for operating the piston 4 and a mechanism for moving the holder 10. The operation of the drive mechanism 12 is controlled by the control section 14. The control section 14 is realized by a general-purpose personal computer or a dedicated computer.

[0044] A plurality of volatile liquid containers 16 that contain a volatile liquid and a plurality of low volatile liquid containers 18 that contain a low volatile liquid are provided in positions lower than the pipettes 2 in a manner corresponding to each of the pipettes 2.

[0045] As the volatile liquid contained in the volatile liquid container 16, there can be listed acetonitrile, methanol, ethanol, acetone, toluene, isopropanol, hexane, butanol, cyclohexane, ethylene glycol, benzene, chloroform, acetaldehyde, triethylamine, phenol, naphthalene, formaldehyde, tetrahydrofuran, ethyl acetate, and the like, and a liquid containing such a liquid at 10% or more.

[0046] As the low volatile liquid contained in the low volatile liquid container 18, there can be listed water, dimethyl sulfoxide, glycerol, and phenol. The low volatile liquid contained in the low volatile liquid container 18 is used when a desired amount of the above-mentioned volatile liquid is measured by the pipette 2.

[0047] The control section 14 is configured in such a manner that it controls the drive mechanism 12 to perform the following operations when a liquid is sucked in. The series of operations for sucking in a liquid are explained together with the flowchart used in Figure 1 Figure 2

[0048] When the operation of sucking in a liquid is started, first, it is confirmed whether the liquid to be sucked in is a volatile liquid. In order to confirm whether it is a volatile liquid, for example, a list of volatile liquids is stored in a storage area such as a data memory provided in the control section 14, and the liquid to be sucked in is compared with the list, whereby it is determined whether the liquid to be sucked in is a volatile liquid.

[0049] ​​If the liquid to be sucked is not a volatile liquid, only a prescribed amount of the liquid is sucked from the suction / discharge port of the tip of each pipette 2. As a result, only a prescribed amount of the liquid to be sucked is collected in the tip 8 attached to the tip of each pipette 2. The liquid collected in each tip 8 is subsequently dispensed into a prescribed dispensing container.

[0050] On the other hand, if the liquid to be sucked is a volatile liquid, first, a low-volatile liquid sucking operation is performed. In the low-volatile liquid sucking operation, the pipette 2 is moved to a position corresponding to the low-volatile liquid container 18, the tip 8 of each pipette 2 is inserted into the low-volatile liquid container 18, and a predetermined amount of low-volatile liquid is sucked from each low-volatile liquid container 18.

[0051] After the above low-volatile liquid sucking operation, an air sucking operation is performed. In the air sucking operation, each pipette 2 is driven to suck air in a state in which the tip 8 of the tip of each pipette 2 is pulled out of the low-volatile liquid container 18, and a predetermined amount of air is sucked into each pipette 2. As a result, an air layer is formed below the low-volatile liquid layer in the pipette 2. Hereinafter, the low-volatile liquid sucking operation and the air sucking operation are collectively referred to as "pre-sucking".

[0052] After the above pre-sucking, a volatile liquid sucking operation is performed. In the volatile liquid sucking operation, the pipette 2 is moved to a position corresponding to the volatile liquid container 16 in which the volatile liquid to be sucked is contained, and a prescribed amount of volatile liquid is sucked from each volatile liquid container 16.

[0053] Thus, by sequentially performing the low-volatile liquid sucking operation, the air sucking operation, and the volatile liquid sucking operation, that is, by performing pre-sucking before the volatile liquid sucking operation, as shown in (A) of FIG. 1, in the tip 8 of the pipette 2, a low-volatile liquid layer, an air layer, and a volatile liquid layer are sequentially formed from the base end side of the tip 8. Figure 3

[0054] When the volatile liquid is sucked from the tip of the tip 8 without performing the above pre-sucking, as shown in (B) of FIG. 1, a large volume of air layer exists between the volatile liquid and the piston 6. When the volume of the air layer between the volatile liquid and the piston 6 is large, the air layer significantly expands due to the influence of the volatilization of the volatile liquid, and thus the volatile liquid is squeezed out and liquid leakage occurs. Figure 3

[0055] In this embodiment, by performing pre-sucking before the volatile liquid sucking operation, the volume of the air layer that expands due to the volatilization of the volatile liquid is smaller than in the case in which pre-sucking is not performed, and thus the expansion volume of the air layer due to the influence of the volatilization of the volatile liquid is also small, and liquid leakage from the tip of the tip 8 is less likely to occur. ​​

[0056] Figure 4 The images of the tip taken immediately after the 70% ACN solution was sucked in (0 seconds) and after 60 seconds from the time the 70% ACN solution was sucked in were obtained for each of the case where pre-suction was performed (A) and the case where pre-suction was not performed (B).

[0057] In this verification, as the liquid handling device, an automatic dispensing device Bravo (product of Agilent) was used, and as the tip, a tip for 2-250 μL was attached to the front end of the pipette of the device. In the case of "with pre-suction" of (A), first, 3 μL of air was sucked in (pre-suction) after 10 μL of water as a low volatile liquid was sucked in, and then 2 μL of a 70% ACN solution (70% ACN / 30% H2O v / v) was sucked in. In the case of "without pre-suction" of (B), 2 μL of a 70% ACN solution (70% ACN / 30% H2O v / v) was sucked in without pre-suction.

[0058] As a result of this verification, in both the case of "with pre-suction" and the case of "without pre-suction", the same degree of 70% ACN solution was present at the front end of the tip immediately after the 70% ACN solution was sucked in (0 seconds). However, after 60 seconds from the time the 70% ACN solution was sucked in (60 seconds later), in the case of "with pre-suction", the 70% ACN solution at the front end of the tip hardly decreased, and no liquid leakage from the front end of the tip was observed, on the other hand, in the case of "without pre-suction", the 70% ACN solution at the front end of the tip greatly decreased, and liquid leakage from the front end of the tip was confirmed. Therefore, it was confirmed from the results of this verification that by performing pre-suction, liquid leakage from the front end of the tip can be suppressed.

[0059] Figure 5 A graph showing the results of verification of the standard curve of the peptide obtained by serial dilution in the case where pre-suction was performed and in the case where pre-suction was not performed. The solid line is the case where pre-suction was performed, and the dashed line is the case where pre-suction was not performed.

[0060] In this verification, Aβ1-38 peptide (2000 amol / μL) dissolved in a 70% acetonitrile (ACN) solution was serially diluted with a 70% ACN solution. Theoretically, the concentration of the Aβ1-38 peptide became 1000 amol / μL, 500 amol / μL, 250 amol / μL, 125 amol / μL, 62.5 amol / μL. In the 70% ACN solution, 250 amol / μL of stable isotope-labeled Aβ1-38 peptide (SIL-Aβ1-38) was dissolved as an internal standard for normalizing the Aβ1-38 signal measured by a mass spectrometer (MALDI-TOF MS). The solutions diluted by each method were sequentially applied to a μFocus MALDI plate TM900 μm, 1 μL was added, and it was dried. 3 wells were added for each solution, and then measured by MALDI-TOF MS.

[0061] Mass spectrometry data was obtained using AXIMA Performance (Shimadzu / KRATOS, Manchester, UK) in Linear TOF in positive ion mode. The m / z value of Linear TOF was represented by the average mass of the peak. As for the m / z value, human angiotensin II and human ACTH fragment 18-39, bovine insulin oxidized beta-chain, bovine insulin were used as external standards for calibration.

[0062] The result obtained by normalizing the signal of the resulting Aβ1-38 with the signal of SIL-Aβ1-38 was set as the normalized intensity. A standard curve was prepared using the Aβ1-38 concentration and the normalized intensity, and the case where pre-suction was performed was compared with the case where pre-suction was not performed. In the case where pre-suction was not performed, the normalized intensity when the concentration was diluted 2 times decreased by more than 1 / 2, and the linearity was not drawn. On the other hand, in the case where pre-suction was performed, the normalized intensity when the concentration was diluted 2 times also decreased to 1 / 2, and the linearity was drawn. The determination coefficient (R 2 ) in the linear regression equation was R 2 = 0.9718 in the usual method, and on the other hand, R 2 = 0.9993 in the case where pre-suction was performed, thereby showing that it was fitted to a straight line by performing pre-suction. This result shows that in the case where pre-suction was not performed, the solution was injected in an amount less than the intended amount due to the leakage, and in the case where pre-suction was performed, the leakage was suppressed, and the solution was accurately injected in an amount equivalent to the intended amount.

[0063] From the above results, it was shown that by performing pre-suction, the leakage from the tip of the pipette 2 was suppressed, and the measurement accuracy of the volatile liquid was improved.

[0064] Figure 6 to Figure 12 Figures showing the verification results of the relationship between the amount of air suction in pre-suction and the leakage suppression effect. These images were obtained by photographing the suction head installed at the lower end of the barrel from an oblique lower side. In this verification, 2 μL Figure 6 ), 3 μL Figure 7 ), 5 μL Figure 8 ), 10 μL Figure 9 ), 50 μL Figure 10), 100μL ( Figure 11 ), 150μL ( Figure 12 The pipette tip was then filled with air, followed by 2 μL of 70% ACN solution. The condition of the pipette tip was observed after 60 seconds.

[0065] In this validation, when the air intake volume was less than 10 μL, there was virtually no decrease in the 70% ACN solution in the pipette tip after 60 seconds, indicating that leakage was suppressed. However, when the air intake volume was 50 μL and 100 μL, a decrease in the 70% ACN solution in the pipette tip was observed after 60 seconds, indicating that leakage occurred.

[0066] This validation confirmed that while pre-inhalation can suppress leakage of volatile liquids, if the volume of the air layer between the low-volatility liquid and the volatile liquid increases, the expansion volume caused by the evaporation of the volatile liquid also increases, reducing the leakage suppression effect. It was confirmed that under the conditions used in this validation, if the air intake volume is below 10 μL, the reduction in volatile liquid is suppressed to within 10% of the intake volume, achieving a sufficient leakage suppression effect. It should be noted that the air intake volume during pre-inhalation can be adjusted appropriately based on the volatility of the volatile liquid and the intake volume.

[0067] The above description uses a liquid processing apparatus having multiple pipettes 2 as an example, but the processing method and liquid processing apparatus of the present invention are not limited thereto, and can also be applied to a processing method and liquid processing apparatus using only one pipette.

[0068] Furthermore, the processing method of the present invention can be implemented not only in liquid processing apparatuses as described in the above embodiments, but also in cases where liquid processing is performed by manually operating a pipette.

[0069] Explanation of reference signs

[0070] 2. Pipettes

[0071] 4 tubes

[0072] 6 Pistons

[0073] 8 suction heads

[0074] 10 Retaining parts

[0075] 12 Drive mechanism

[0076] 14 Control Department

[0077] 16 Containers for volatile liquids

[0078] 18. Containers for low-volatility liquids

Claims

1. A method for treating a liquid to be aspirated, comprising using a pipette, the pipette having a barrel, a piston sliding within the barrel, and a pipette tip mounted at the front end of the barrel, the pipette tip having an intake / exhaust port, and the pipette changing the amount of air filling the barrel by operation of the piston, thereby drawing liquid into the pipette tip and expelling liquid from the pipette tip via the intake / exhaust port, the method comprising a liquid aspiration step of drawing the liquid to be aspirated from the intake / exhaust port. Only when the liquid to be inhaled is a volatile liquid, the treatment method further includes, prior to the liquid inhalation step: The low-volatility liquid inhalation step involves inhaling a low-volatility liquid with a lower volatility than the liquid to be inhaled from the inhalation / exhaust port. as well as, The air intake step involves drawing air in from the intake / exhaust port after the low-volatility liquid intake step. The low-volatility liquids mentioned above refer to substances with a boiling point above 95°C that are liquid at room temperature, and... The volatile liquids mentioned above refer to substances with a boiling point in the range of 50–95°C that are liquid at room temperature, or liquids containing more than 10% of such substances. When the air intake is less than 10 μL, the reduction in the volatile liquid is suppressed to within 10% of the intake.

2. The processing method according to claim 1, wherein, The amount of air inhaled from the intake / exhaust port in the air intake step is determined based on the volatility of the liquid to be inhaled and the amount of liquid to be inhaled in the volatile liquid intake step.

3. The processing method according to claim 1 or 2, further comprising: The confirmation step involves confirming whether the liquid to be inhaled is a volatile liquid; as well as The procedure involves determining whether to perform the low-volatility liquid inhalation step and the air inhalation step.

4. The processing method according to claim 1 or 2, wherein, The low-volatility liquid is any one of water, dimethyl sulfoxide, glycerol, and phenol.

5. The processing method according to claim 1 or 2, wherein, The volatile liquid is any liquid selected from acetonitrile, methanol, ethanol, acetone, toluene, isopropanol, hexane, butanol, cyclohexane, ethylene glycol, benzene, chloroform, acetaldehyde, triethylamine, phenol, naphthalene, formaldehyde, tetrahydrofuran, and ethyl acetate, or a liquid containing more than 10% of them.

6. A liquid handling apparatus comprising: A pipette includes: a cylinder arranged in a vertical direction, a piston that slides vertically inside the cylinder, and a pipette tip. The pipette tip is mounted at the lower end of the cylinder with its suction / discharge port facing downwards. The pipette changes the amount of air filling the cylinder by operating the piston, thereby allowing liquid to be drawn into the pipette tip and discharged from the pipette tip via the suction / discharge port. A drive mechanism for operating the pipette; A liquid container that holds the liquid to be inhaled; A container for low-volatility liquids, which contains low-volatility liquids with lower volatility than volatile liquids; as well as, The control unit is used to control the drive mechanism. Only when the liquid to be inhaled is a volatile liquid, the control unit is configured to control the drive mechanism to perform the following operations: a low-volatility liquid inhalation operation, inhaling a predetermined amount of the low-volatility liquid from the low-volatility liquid container; and an air inhalation operation, inhaling a predetermined amount of air from the inhalation / exhaust port after performing the low-volatility liquid inhalation operation and before performing a liquid inhalation operation that inhales a predetermined amount of the liquid to be inhaled from the liquid container. The low-volatility liquids mentioned above refer to substances with a boiling point above 95°C that are liquid at room temperature, and... The volatile liquids mentioned above refer to substances with a boiling point in the range of 50–95°C that are liquid at room temperature, or liquids containing more than 10% of such substances. When the air intake is less than 10 μL, the reduction in the volatile liquid is suppressed to within 10% of the intake.

7. The liquid handling apparatus according to claim 6, wherein, The amount of air intake in the air intake operation is determined based on the volatility of the liquid to be inhaled and the amount of liquid to be inhaled in the volatile liquid intake operation.

8. The liquid handling apparatus according to claim 6 or 7, wherein, The control unit stores a list of volatile liquids and is configured to determine whether the liquid to be inhaled is a volatile liquid based on the list.

9. The liquid handling apparatus according to claim 6 or 7, wherein, The low-volatility liquid is any one of water, dimethyl sulfoxide, glycerol, and phenol.

10. The liquid handling apparatus according to claim 6 or 7, wherein, The volatile liquid is any liquid selected from acetonitrile, methanol, ethanol, acetone, toluene, isopropanol, hexane, butanol, cyclohexane, ethylene glycol, benzene, chloroform, acetaldehyde, triethylamine, phenol, naphthalene, formaldehyde, tetrahydrofuran, and ethyl acetate, or a liquid containing more than 10% of them.

Images