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WO1992008545A1 - Procede de prelevement d'echantillons par pipette - Google Patents

Procede de prelevement d'echantillons par pipette Download PDF

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Publication number
WO1992008545A1
WO1992008545A1 PCT/US1991/008375 US9108375W WO9208545A1 WO 1992008545 A1 WO1992008545 A1 WO 1992008545A1 US 9108375 W US9108375 W US 9108375W WO 9208545 A1 WO9208545 A1 WO 9208545A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample
pipettor
pressure
aspiration
fluid
Prior art date
Application number
PCT/US1991/008375
Other languages
English (en)
Inventor
Charles W. Brentz
Original Assignee
Abbott Laboratories
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Laboratories filed Critical Abbott Laboratories
Priority to KR1019930701367A priority Critical patent/KR930702072A/ko
Priority to JP4501066A priority patent/JP3065100B2/ja
Priority to AU90758/91A priority patent/AU652014B2/en
Priority to CA002095152A priority patent/CA2095152C/fr
Publication of WO1992008545A1 publication Critical patent/WO1992008545A1/fr
Priority to US08/222,501 priority patent/US5463895A/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F23/00—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm
    • G01F23/14—Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm by measurement of pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/025—Displaying results or values with integrated means
    • B01L2300/027—Digital display, e.g. LCD, LED
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • G01N2035/1018—Detecting inhomogeneities, e.g. foam, bubbles, clots
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025—Fluid level sensing

Definitions

  • This invention relates generally to a non-invasive automated pipetting method, and more particularly, relates to determining the level of fluid present in a test sample.
  • Level sensing is accomplished by moving a pipettor toward a sample while aspirating air and monitoring for a pressure change within the pipettor. Controlled aspiration of the fluid sample is then performed.
  • conducting pipette tip or an electrode adjacent to the pipette tip generates an electrical signal when the conducting pipette tip or the electrode touches the surface of an electrically conducting fluid, such as a buffer solution or serum, plasma or urine sample.
  • an electrically conducting fluid such as a buffer solution or serum, plasma or urine sample.
  • Detecting the surface of a fluid is very important for the precise pipetting of the fluid. Locating the fluid surface permits the controlled immersion of the pipette tip in the fluid. By controlling the depth of immersion of the pipette tip in the fluid, a consistent amount of fluid will cling to the outside of the tip resulting in greater consistency in the total volume dispensed.
  • the use of non-invasive fluid sample surface sensing methods and devices in conjunction with disposable polymeric pipette tips results in such greater control and consistency.
  • non-invasive fluid sample surface sensing achieves two advantages. First, it eliminates the need to wash the pipette tip between sampling, thereby increasing the through put of the instrument. Second, a non-invasive surface probing method eliminates the potential of sample carry-over.
  • a non-invasive fluid surface-sensing system were disclosed in U.S. Patents Nos. 3,474,902 and 3,494,191.
  • This non-invasive fluid surface-sensing system utilizes a method that involves blowing air via a stepper-motor controlled syringe to detect a fluid surface level.
  • This level sensing method can be used in automated pipetting of biological samples.
  • air is often blown into the test sample causing bubbles and generating aerosols.
  • the pipettor is moved toward the sample very slowly until the sample surface is detected, and then immediately withdrawn to the end of its travel range.
  • the syringe is then fully dispensed to blow all the remaining air out of the syringe. Finally, the pipettor is returned to the fluid surface and aspiration is commenced.
  • An object of the present invention is to non-invasively level sense a fluid sample without the need of blowing air through the pipette tip. Another object of the present invention is to aspirate a fluid sample by immersing the pipette tip into the sample at a controlled, minimal depth in order to minimize the amount of sample that clings to the outside of the pipette tip. Yet another object of the present invention is to detect nonhomogeneity, such as clots, bubbles and foam, in the fluid sample. Still other objects of the present invention will be apparent to one skilled in the art.
  • the present invention offers advantages over known methods of level sensing and aspiration of a fluid sample. Carry-over or cross-contamination between samples and reagents is eliminated by employing a non-invasive method in which no contact is made between the level sense means, such as a pressure transducer, and the test sample.
  • the present invention also has advantages over positive pressure (blowing air) level sense methods. The possibility of bubbles and aerosols is eliminated by the present invention. Also, because the need to reverse the direction of the syringe pump between the level sense step and the aspiration step is eliminated, the instrument throughput is increased.
  • the present invention eliminates the necessity of withdrawing the pipettor from the sample in order to evacuate the syringe before aspiration again improving the instrument throughput through the elimination of method steps without the creation of bubbles and aerosols.
  • This invention provides an apparatus and method of pipetting a fluid from a container, which comprises (a) determining the level of the fluid in the container by (i) determining the ambient air pressure within a pipettor as a baseline pressure reading, (ii) aspirating air into the pipettor as the pipettor moves toward the fluid sample in the
  • the tip of the pipettor may be disposable or reusable.
  • the invention also provides an apparatus and method of detecting non-homogeneity in a fluid sample, such as the presence of foam or bubbles on the surface of the sample, and/or the presence of clots on the surface or in the bulk of the test sample.
  • This method comprises (a) determining the ambient air pressure within a pipettor as a baseline pressure reading; (b) aspirating air into the pipettor as the pipettor moves towards a sample in a container; (c) monitoring for an air pressure change in the pipettor to indicate the surface level of the fluid in said container; (d) immersing the pipettor in the fluid and aspirating a volume of fluid from the
  • step (e) monitoring pressure changes after said aspiration of step (d); (f) comparing measured pressure change to predetermined normal aspiration pressure windows; and (g) observing pressure values falling outside said predetermined values.
  • Figure 1 is a graph of a representative sample of normal calf serum using the level sensing method of this invention wherein Pressure (+1 psi to -1 psi represented as 10 bit binary) is plotted against a sequential number of pressure readings taken at periodic intervals. The change in pressure occurs as the pipette tip touches the surface of the sample and the air aspiration is immediately halted.
  • Pressure +1 psi to -1 psi represented as 10 bit binary
  • Figure 2 is a graph of representative pressure changes during aspiration of a sample of normal calf serum using the level sensing and aspiration method of this invention to aspirate 1000 ⁇ L of sample, wherein Pressure (+1 psi to -1 psi represented as 10 bit binary) is plotted against Aspiration Data Points. All of the pressure measurements are within the predetermined aspiration pressure windows indicating a homogeneity in the sample.
  • Figure 3 is a graph of a representative sample of normal calf serum containing foam on the surface using the fluid level sensing and aspiration method of this invention to aspirate 1000 ⁇ L of sample, wherein Pressure (+1 psi to -1 psi represented as 10 bit binary) is plotted against Aspiration Data Points. At least one of the measured pressure values is outside a predetermined aspiration pressure window
  • Figure 4 is a graph of a representative sample of normal calf serum containing large bubbles on the surface using the fluid level sensing and aspiration method of this invention to aspirate 1000 ⁇ L of sample, wherein Pressure (+1 psi to -1 psi represented as 10 bit binary) is plotted against Aspiration Data Points. At least one of the measured pressure values is outside a predetermined aspiration pressure window
  • Figure 5 is a graph of a sample of water containing a non-dairy creamer to simulate clots in the sample using the fluid level sensing and aspiration method of this invention to aspirate 1000 ⁇ L of sample, wherein Pressure (+1 psi to -1 psi represented as 10 bit binary) is plotted against Aspiration Data Points. At least one of the measured pressure values is outside a predetermined aspiration pressure window
  • Figure 6 is a illustration of an apparatus which level senses and aspirates two samples simultaneously followed by dispensing of the two samples into a sample reaction tray.
  • the novel level sensing and aspiration apparatus and method of the present invention is based upon measurable pressure changes within a pipettor during the level sensing and aspiration steps.
  • the present invention was surprisingly found to more rapidly and
  • the pipettor apparatus of the present invention is comprised of a disposable pipette tip 1 0 capable of making an air tight connection with a pipette tip holder means 12 having a bore and a tube connection means 14 capable of making an air tight coupling between tubing 16 and the pipettor such that air can be drawn through the disposable pipette tip 10 into the pipette tip holder means 12 and then into tubing 16.
  • Tubing 16 is connected to a pressure
  • pipette tip holder means 12 is attached to a means (not shown) for moving the pipettor vertically along the Z-axis.
  • Pipette tip holder means 12 are well know in the art.
  • manual and automated pipettors are readily available which have a tip probe that permits the formation of an air tight seal between the pipettor and a disposable pipette tip and at the same time, permit the easy removal of the disposable pipette tip.
  • a limit-switch can be incorporated to detect the presence or absence of a pipette tip on the tip probe, One skilled in the art would be able to prepare such a pipettor without undo experimentation.
  • tube connection means 14 are well known in the art, such as luer-lock, compression fitting tube adaptors and the like, and can be readily adapted by one skilled in the art for use in the present invention without undo experimentation.
  • the disposable pipette tips (10) can be stored in racks which are accessible by the pipettor.
  • Pressure measurement means 18 measures the air pressure within the pipettor either continuously or
  • pressure measurement means is a pressure transducer
  • the pressure transducer is interfaced to a host computer system through a Datem dcm300 Digital I/O Board (available from Datem Limited, Ontario, Canada).
  • the pressure transducer provides a 10-bit binary output (0 to 1023) with an ambient air pressure measuring at approximately the center of the range (512).
  • Full scale pressure (+1 psi) translates to 0 and full scale vacuum (-1 psi) translates to 1023.
  • Means 20 for aspirating air through the pipettor must be capable of precisely controlled movements.
  • the aspiration means (20) must be capable of stopping immediately after the pipette tip reaches the fluid surface.
  • a preferred aspiration means (20) is a syringe, preferably a 1500 ⁇ L syringe, mechanically connected to a stepper motor and home limit-switches capable of controlling the movement of the syringe piston and causing the syringe to aspirate and dispense air through tubing 16.
  • the stepper motor and home limit-switches are interfaced to the host computer through the Datem dcm340 Stepper Motor Control (available from Datem Limited, Ontario, Canada).
  • Means for moving the pipettor vertically along the Z-axis is an electro-mechanical assembly that is capable of at least moving the pipettor along the Z-axis (vertically) relative to the XY-plane of the sample container (22) and may also be capable of moving the pipettor along the X and Y axes.
  • a stepper-motor and home limit-switches are used for positioning the pipettor along the Z-axis.
  • the stepper-motor and home limit-switches are interfaced to the host computer through the Datem dcm340 Stepper Motor Control.
  • a Magnon XY Table (available from Magnon Engineering, Fontana, California) or the like is used for positioning the pipettor.
  • the Magnon XY Table includes both the mechanical hardware and the electronic controls
  • California is used to interface the XY table controller to the host computer.
  • FIG. 6 illustrates dual pipettor assemblies. Each pipettor
  • the assembly comprises a disposable pipette tip 10, pipette tip holder means 12 connected through tubing 16 to a pressure measurement means 18 and an aspiration means 20.
  • the two pipettor assemblies are interfaced with a means for moving both pipettors vertically along the Z-axis such that two samples can be level sensed and aspirated simultaneously or sequentially.
  • These dual pipettor assemblies permit the dispensing of two samples into a reaction tray having dual reaction wells (24) .
  • the sample pipetting method of the present invention involves level sensing of the sample's fluid surface and sample aspiration.
  • the following is a detailed summary of the present invention using the pipettor apparatus shown in Figure 6:
  • the ambient air pressure is measured in the pipettor by a pressure transducer while the syringe is in its fully dispensed position and the pipettor is located at the top of its stroke in the Z axis.
  • the value becomes a baseline to which all other pressure readings are compared. By using this value as a baseline, any effect on the pressure measurements due to changes in the atmospheric pressure are eliminated.
  • the pipettor is moved down toward the test sample until the pipette tip is even with the top of the test sample tube.
  • the pipettor must be stopped so that the tip of the pipettor is not more than 0.125 or 1/8 inch below the surface of the sample. By stopping within 0.125 inches, the amount of sample fluid clinging to the outside of the pipette tip can be more easily minimized.
  • the continuous pressure measurement will actually be recorded as a series of periodic
  • At least about 100 ⁇ L of sample is aspirated into the pipettor by withdrawing the syringe the appropriate distance.
  • the pressure in the pipettor is measured (see Fig. 2, Aspiration Data Point 1).
  • the pressure is again measured after the pressure has reached equilibrium, i.e. a steady state pressure (about 0.2 seconds) (see Fig. 2, Aspiration Data Point 2).
  • Step 8 the pipetting is continued with Step 8.
  • the aspiration pressure windows are calculated from the ambient pressure measurement taken in Step 1 above by adding empirically determined values to the ambient pressure measurement (see Table 1).
  • the empirically determined values are obtained using standard experimental methods known in the art, i.e. a variety of normal, homogeneous samples are pipetted using the sample pipetting method herein with a variety of pressure transducers.
  • transducers are known to differ in their individual performance characteristics and by establishing a normal range, i.e. aspiration pressure windows, variations between different transducers and
  • a nonhomogeneous sample is a sample that has at least one pressure measurement that falls outside the aspiration pressure windows which are the ranges within which the pressure measurements of normal, homogeneous samples will fall.
  • the empirically determined values are simply obtained by subtracting the ambient pressure (at the time of the normal sample pressure measurements) from the highest and lowest pipettor pressure measurements obtained during the sample pipetting of the normal samples. Thus, these empirical values when added to the ambient pressure in some future sample pipetting will automatically be adjusted for any variation in the ambient pressure at the time of the future sample pipetting.
  • the pipettor is then lowered further into the sample a short distance (approximately 0.055 inches) to avoid starving the pipettor of sample during sample aspiration.
  • the pressure measurement value is then compared with aspiration pressure windows. If at least one pressure value is outside the corresponding window, the sample is nonhomogeneous and the pipetting is halted. If the value is within the windows, the pipetting is continued with Step 11.
  • Steps 8-10 i.e. an aspiration cycle (see Fig. 2,
  • Aspiration Data Points 4-8) are repeated, if necessary, until the total desired amount of sample is aspirated into the pipettor (from about 100 ⁇ L to about 1000 ⁇ L).
  • the pipettor is moved up a short distance
  • the pipettor is then moved slowly up about 0.5 inches to prevent shearing off of a small amount of sample from inside the pipettor tip.
  • the pipettor is then moved to the home position from which the pipettor can be moved to a dispensing location and is ready to dispense an accurate amount of sample into a reaction vessel.
  • the pipettor is moved downward toward the fluid sample's surface simultaneously with aspiration of air into the pipettor.
  • the syringe used in this method is a 1500 ⁇ L syringe.
  • the preferred syringe speed for the level sensing method is 160 ⁇ L per second and the speed of the pipettor is adjusted so that the pipettor reached the end of its stroke (i.e.
  • the pipettor's downward speed should preferably be less than the maximum speed so that the pipettor can be stopped such that the end of the pipette tip is no more than 0.125 (1/8) inch below the surface of the sample.
  • the delay in the pipettor's movement preferably for about 0.2 seconds, gives the air pressure time to reach steady state.
  • the aspiration method begins after the sample surface has been level sensed and the pipette tip is located no more than about 0.125 inches below the sample's surface. Both the syringe and the pipettor are stationary. The pipettor is moved down a short distance, preferably about 0.055 inches, to prevent the pipettor from being starved for sample during aspiration. If the pipettor is starved for sample, air will be aspirated along with sample and an erroneous amount of sample will have been aspirated. At least 100 ⁇ L of sample is then aspirated (first aspiration). It is believed that about 100 ⁇ L of sample is the minimum amount of sample that can be accurately aspirated by this protocol using the apparatus shown in Figure 6. This amount of sample provides a
  • a pressure reading is taken (Aspiration Data Point 1). If this pressure reading is outside the aspiration pressure window for Aspiration Data Point 1 , the sample is non-homogeneous. For example, a sample with high viscosity, such as a sample with clots or thick foam, will cause a higher vacuum to be created within the pipettor than a normal homogeneous sample. A sample with bubbles or a leak in the system will result in a lower vacuum within the pipettor than a normal homogeneous sample and may even read at ambient pressure.
  • a second aspiration pressure reading (Aspiration Data Point 2) is taken within the pipettor after a short delay, preferably at least about 0.2 seconds, which is sufficient time for the pressure within the pipettor to reach a steady state.
  • a pressure reading outside the aspiration pressure window corresponding to Aspiration Data Point 2 is an indication of non-homogeneity or problems with the system. Whenever any pressure reading is outside the corresponding aspiration pressure window, the aspiration process is stopped automatically.
  • sample aspiration cycles wherein a set volume (or less if that is all that is needed to obtain the desired amount of total sample aspirated),
  • An aspiration cycle includes the following: (1 ) moving the pipettor downward into the sample a short distance,
  • the aspiration pressure windows are empirically derived values.
  • a number of normal homogeneous fluid samples are aspirated using the present invention method using different lots of pressure measurement means.
  • the normal fluctuations in the pressure readings (Aspiration Data Points) due to variations in the samples and pressure measurement means will establish a normal range of pressure values that can be expected to be observed when aspirating normal homogeneous samples.
  • the range at each Aspiration Data Point extends from the lowest pressure reading value to the highest pressure reading value obtained when the normal homogeneous samples were aspirated.
  • the ambient pressure (at the time of the aspiration) is subtracted from the lowest and highest pressure reading values obtained at each Aspiration Data Point.
  • the differential values at each Aspiration Data Point obtained from ten samples of normal calf serum are listed in Table 1.
  • the aspiration pressure windows in future aspirations can then be calculated from these differential values by adding the ambient pressure measured at the beginning of the level sensing steps (step 1 above). The accuracy of these ranges (i.e. the differential values) will be dependant upon the number of normal samples used to establish the aspiration pressure windows. Preferably at least ten (10) samples should be used to establish the
  • the sample is non- homogeneous and the aspiration is halted.
  • the aspiration pressure window values according to the values in Table 1 would be from 752 (512 + 240) to 882 (512 + 370).
  • a sample pressure reading value less than 752 or greater than 882 would indicate that the sample is non-homogeneous.
  • the pipettor is moved upward a short distance, preferably about 0.055 inches, so that the end of the pipette tip is within 0.125 inches below the surface of the sample. This permits some of the sample, preferably about 50 ⁇ L, to be dispensed back into the sample. Because mechanical systems have a looseness in the mechanical connections, such as slippage between gears and the like, a backlash is observed when the mechanism driving the syringe piston is reversed in direction from its former movement. For example, when approximately 50 ⁇ L of sample is dispensed back into the sample, some of the mechanical movement readjusts the tension between the parts before the syringe piston begins to move. Thus, less than 50 ⁇ L of sample is actually dispensed back into the sample.
  • a short delay preferably at least 0.5 seconds, permits much of the sample fluid clinging to the outside of the pipette tip to run off.
  • the pipettor is then moved a short distance upward, preferably at least about 0.5 inches, at a very slow rate, preferably no more than 2.88 inches per second. This permits the removal of the pipette tip from the sample without shearing off or loosing a small amount of sample from inside the end of the pipette tip.
  • the pipettor can then be returned to the home position at normal speed. From the home position the pipettor is moved to a new location where dispensing of the aspirated sample occurs. Alternatively, the reaction tray is moved in place of the sample container and the pipettor is again moved downward.
  • a sample must be at least partially liquid to be
  • a sample can be a liquid biological fluid such as blood, serum, plasma, urine, cerebrospinal fluid, ascites fluid, cell growth media, tissue and swab extracts, fluids resulting from sample processing in DNA cyclizers, and the like.
  • the biological sample can contain particles such as cells and the like. The particles can also include microparticles or other small particles used in assay procedures.
  • a sample can also be a non-biological fluid such as water samples, or any chemical or solid which can be at least dispersed in a liquid suspension.
  • a vacuum was created within the pipettor shown in Figure 6 by aspirating air into the pipettor (with a syringe) as the pipettor was moved toward the sample surface.
  • the pressure was monitored during this process with a pressure transducer and the data was stored in the variable named "p_array".
  • the sample was goat plasma.
  • the pipettor control software was executed under the control of the Soft-Scope 286 Debugger program (available from Concurrent Sciences, Moscow, Idaho). This software package has the ability to monitor execution of the program and examine the values of variables during processing. After level sensing was
  • Table 2 The values in Table 2 are 10-bit binary where full scale vacuum (-1 psi) has a value of 1023 and full scale pressure (+1 psi) has a value of 0.
  • the change in pressure at reading number 14 indicates that the surface has been reached, i.e. the tip of the pipettor has touched the sample surface.
  • the aspiration pressure windows were verified using normal calf serum as follows. Ten samples of normal calf serum were individually aspirated and the pipettor aspiration pressure data was saved. All ten samples were visually verified to contain no foam, bubbles, dots or other nonhomogeneity. All ten samples were level sensed within 0.125 (1/8) inches of the sample surface, and thus fell within the allowed window of 0.125 inches from the sample surface.
  • the aspiration data from all ten samples is summarized in Table 3.
  • a representative sample is graphed in Figure 2, wherein pressure (+1 psi to -1 psi represented as 10-bit binary) is plotted against aspiration data points.
  • One calf serum sample shown as the solid line between closed squares, was plotted. Also plotted was the low limit windows, graphed as the solid line between crosses, and the high limit windows, shown as the solid line between asterisks.
  • the aspiration data from all three samples is summarized in Table 4.
  • the data from one of the calf serum samples containing foam (shown as the solid line between closed squares) is graphed in Figure 3, wherein pressure (+1 psi to -1 psi represented as 10-bit binary) is plotted against aspiration data points. Also plotted was the low limit windows, graphed as the solid line between crosses, and the high limit windows, shown as the solid line between asterisks.
  • the sample was rejected on the basis of the initial aspiration data point and aspiration was halted.
  • the bubbles of the third sample hindered the sample surface level sense.
  • the bubbles and not the sample surface were detected when the bubbles were contacted by the pipettor.
  • This sample was rejected on the basis of the aspiration pressure data.
  • the third sample aspiration data is graphed in Figure 4 (shown as the solid line between closed squares), wherein pressure (+1 psi to -1 psi represented as 10-bit binary) is plotted against aspiration data points. Also plotted was the low limit windows, graphed as the solid line between
  • Figure 5 is a graph of a representative sample (shown as the solid line between closed squares), wherein pressure (+1 psi to -1 psi represented as 10-bit binary) is plotted against aspiration data points. Also plotted was the low limit windows, graphed as the solid line between crosses, and the high limit windows, shown as the solid line between asterisks.

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  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Fluid Mechanics (AREA)
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  • Sampling And Sample Adjustment (AREA)
  • Analysing Materials By The Use Of Radiation (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Abstract

Procédé de type non invasion de détermination de la quantité de fluide présente dans une prise d'essai. On détermine la quantité de fluide présente dans une prise d'essai située dans un récipient (22) en déplaçant une pipette (10) en direction de la surface de l'échantillon tout en aspirant l'air et en contrôlant les modifications de pression à l'aide d'un détecteur (18). On peut détecter le caractère éventuellement non homogène de l'échantillon pendant l'aspiration.
PCT/US1991/008375 1990-11-09 1991-11-08 Procede de prelevement d'echantillons par pipette WO1992008545A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
KR1019930701367A KR930702072A (ko) 1990-11-09 1991-11-08 샘플 피펫계량법
JP4501066A JP3065100B2 (ja) 1990-11-09 1991-11-08 サンプルのピペッティング法
AU90758/91A AU652014B2 (en) 1990-11-09 1991-11-08 Sample pipetting method
CA002095152A CA2095152C (fr) 1990-11-09 1991-11-08 Methode d'aspiration d'un echantillon par pipette
US08/222,501 US5463895A (en) 1990-11-09 1994-04-04 Sample pipetting method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US61216090A 1990-11-09 1990-11-09
US612,160 1990-11-09

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Publication Number Publication Date
WO1992008545A1 true WO1992008545A1 (fr) 1992-05-29

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PCT/US1991/008375 WO1992008545A1 (fr) 1990-11-09 1991-11-08 Procede de prelevement d'echantillons par pipette

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EP (1) EP0556336A1 (fr)
JP (1) JP3065100B2 (fr)
KR (1) KR930702072A (fr)
AU (1) AU652014B2 (fr)
CA (1) CA2095152C (fr)
WO (1) WO1992008545A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
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EP0682258A1 (fr) * 1994-05-09 1995-11-15 Ciba Corning Diagnostics Corp. Circuit pour détecter l'obstruction d'une sonde de prélèvement d'échantillons
WO1996041200A1 (fr) * 1995-06-07 1996-12-19 Abbott Laboratories Appareil de pipettage automatique avec detection de fuites et procede pour detecter les fuites
WO1997022007A1 (fr) * 1995-12-14 1997-06-19 Abbott Laboratories Manipulateur de fluide et procede de manipulation d'un fluide
EP0726466A4 (fr) * 1993-08-31 1997-07-02 Aloka Co Ltd Appareil de pipettage dote d'une fonction de detection de fermeture
EP0753750A3 (fr) * 1995-07-13 1997-09-24 Ciba Corning Diagnostics Corp Procédé et dispositif pour aspirer et remettre des échantillons liquides
WO1998053326A1 (fr) * 1997-05-22 1998-11-26 Abbott Laboratories Procede de manipulation de fluide
WO1998053325A1 (fr) * 1997-05-22 1998-11-26 Abbott Laboratories Procede et dispositif de manipulation d'une fluide
EP0930495A4 (fr) * 1996-10-03 1999-07-21
US6158269A (en) * 1995-07-13 2000-12-12 Bayer Corporation Method and apparatus for aspirating and dispensing sample fluids
EP1269140A4 (fr) * 2000-03-28 2003-05-02 Caliper Techn Corp Procedes permettant de reduire un report fluidique dans des dispositifs microfluidiques
WO2002073215A3 (fr) * 2001-03-09 2004-02-26 Hamilton Bonaduz Ag Procede et dispositif d'evaluation d'un processus de dosage de liquide
EP2031403A1 (fr) 2007-08-27 2009-03-04 Roche Diagnostics GmbH Procédé de surveillance d'un procédé de transfert de fluides
EP1306675A4 (fr) * 2000-06-30 2010-07-28 Hitachi Ltd Procede et dispositif de distribution de liquide
DE102011081186A1 (de) * 2011-08-18 2013-02-21 Hamilton Bonaduz Ag Verfahren zum Detektieren der Oberfläche einer Flüssigkeitsprobe in einem Probenbehälter
EP2759835A4 (fr) * 2011-09-20 2015-04-22 Hitachi High Tech Corp Dispositif d'analyse automatique et procédé de détermination de son dysfonctionnement
US9696328B2 (en) 2002-05-17 2017-07-04 Becton, Dickinson And Company Automated system for isolating, amplifying and detecting a target nucleic acid sequence
US20220146540A1 (en) * 2019-03-15 2022-05-12 Hitachi High-Tech Corporation Automatic analysis device

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JP4677076B2 (ja) * 2000-04-19 2011-04-27 アークレイ株式会社 液面検知装置
JP5122949B2 (ja) 2005-05-19 2013-01-16 ユニバーサル・バイオ・リサーチ株式会社 分注量検出方法および吸液モニタ型分注装置
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FR2977317B1 (fr) * 2011-06-28 2013-08-02 Gilson Sas Procede de detection d'anomalies lors du remplissage d'un dispositif de dosage de liquide et dispositif de dosage de liquide

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Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0726466A4 (fr) * 1993-08-31 1997-07-02 Aloka Co Ltd Appareil de pipettage dote d'une fonction de detection de fermeture
US5503036A (en) * 1994-05-09 1996-04-02 Ciba Corning Diagnostics Corp. Obstruction detection circuit for sample probe
EP0682258A1 (fr) * 1994-05-09 1995-11-15 Ciba Corning Diagnostics Corp. Circuit pour détecter l'obstruction d'une sonde de prélèvement d'échantillons
WO1996041200A1 (fr) * 1995-06-07 1996-12-19 Abbott Laboratories Appareil de pipettage automatique avec detection de fuites et procede pour detecter les fuites
US6158269A (en) * 1995-07-13 2000-12-12 Bayer Corporation Method and apparatus for aspirating and dispensing sample fluids
EP1329725A3 (fr) * 1995-07-13 2003-08-27 Bayer Corporation Procédé pour la détection de fuites dans un système d'aspiration et de distribution
EP0753750A3 (fr) * 1995-07-13 1997-09-24 Ciba Corning Diagnostics Corp Procédé et dispositif pour aspirer et remettre des échantillons liquides
US5750881A (en) * 1995-07-13 1998-05-12 Chiron Diagnostics Corporation Method and apparatus for aspirating and dispensing sample fluids
WO1997022007A1 (fr) * 1995-12-14 1997-06-19 Abbott Laboratories Manipulateur de fluide et procede de manipulation d'un fluide
EP0930495A4 (fr) * 1996-10-03 1999-07-21
US6063635A (en) * 1996-10-03 2000-05-16 Abbott Laboratories Dispensing method for automatic sample analysis systems
WO1998053325A1 (fr) * 1997-05-22 1998-11-26 Abbott Laboratories Procede et dispositif de manipulation d'une fluide
WO1998053326A1 (fr) * 1997-05-22 1998-11-26 Abbott Laboratories Procede de manipulation de fluide
EP1269140A4 (fr) * 2000-03-28 2003-05-02 Caliper Techn Corp Procedes permettant de reduire un report fluidique dans des dispositifs microfluidiques
EP1306675A4 (fr) * 2000-06-30 2010-07-28 Hitachi Ltd Procede et dispositif de distribution de liquide
WO2002073215A3 (fr) * 2001-03-09 2004-02-26 Hamilton Bonaduz Ag Procede et dispositif d'evaluation d'un processus de dosage de liquide
US6938504B2 (en) 2001-03-09 2005-09-06 Hamilton Bonaduz Ag Method and device for evaluating a liquid dosing process
US9696328B2 (en) 2002-05-17 2017-07-04 Becton, Dickinson And Company Automated system for isolating, amplifying and detecting a target nucleic acid sequence
EP2031403A1 (fr) 2007-08-27 2009-03-04 Roche Diagnostics GmbH Procédé de surveillance d'un procédé de transfert de fluides
US7917313B2 (en) 2007-08-27 2011-03-29 Roche Molecular Systems, Inc. Method for monitoring a fluid transfer process
DE102011081186A1 (de) * 2011-08-18 2013-02-21 Hamilton Bonaduz Ag Verfahren zum Detektieren der Oberfläche einer Flüssigkeitsprobe in einem Probenbehälter
EP2759835A4 (fr) * 2011-09-20 2015-04-22 Hitachi High Tech Corp Dispositif d'analyse automatique et procédé de détermination de son dysfonctionnement
US9470570B2 (en) 2011-09-20 2016-10-18 Hitachi High-Technologies Corporation Automatic analyzer and method for determining malfunction thereof
US20220146540A1 (en) * 2019-03-15 2022-05-12 Hitachi High-Tech Corporation Automatic analysis device
US12188952B2 (en) * 2019-03-15 2025-01-07 Hitachi High-Tech Corporation Automatic analysis device

Also Published As

Publication number Publication date
CA2095152C (fr) 2003-02-18
KR930702072A (ko) 1993-09-08
EP0556336A4 (fr) 1994-02-23
JP3065100B2 (ja) 2000-07-12
JPH06501558A (ja) 1994-02-17
AU9075891A (en) 1992-06-11
CA2095152A1 (fr) 1992-05-10
AU652014B2 (en) 1994-08-11
EP0556336A1 (fr) 1993-08-25

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