CA1151894A - Method and apparatus for metering biological fluids - Google Patents
Method and apparatus for metering biological fluidsInfo
- Publication number
- CA1151894A CA1151894A CA000377890A CA377890A CA1151894A CA 1151894 A CA1151894 A CA 1151894A CA 000377890 A CA000377890 A CA 000377890A CA 377890 A CA377890 A CA 377890A CA 1151894 A CA1151894 A CA 1151894A
- Authority
- CA
- Canada
- Prior art keywords
- tip
- metering
- fluid
- slide
- dispenser
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
Classifications
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
-
- 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
- G01N35/1011—Control of the position or alignment of the transfer device
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/119163—Automated chemical analysis with aspirator of claimed structure
Abstract
-i-METHOD AND APPARATUS FOR METERING BIOLOGICAL FLUIDS
ABSTRACT OF THE DISCLOSURE
A method and apparatus are disclosed for repeatedly and accurately depositing predetermined amounts of fluid, especially biological fluids, onto generally planar analysis slides. The apparatus comprises a dispenser which is adapted to pick up a disposable metering tip, aspirate fluid into the tip, meter a predetermined amount of fluid from the tip onto an analysis slide, and eject the tip after the metering operation.
ABSTRACT OF THE DISCLOSURE
A method and apparatus are disclosed for repeatedly and accurately depositing predetermined amounts of fluid, especially biological fluids, onto generally planar analysis slides. The apparatus comprises a dispenser which is adapted to pick up a disposable metering tip, aspirate fluid into the tip, meter a predetermined amount of fluid from the tip onto an analysis slide, and eject the tip after the metering operation.
Description
~ii3L89~
BACKGROU~iD OF THE I~VENTIO~;
lo Field of the Invention This invention relates to the chemical analysis of substances, and more particularly to a method and apparatus for the precise metering of biological fluids onto test elements.
State of the Prior Art A number of automated systems have been aeveloped for performing quantitative chemical analyses of fluid samples. Most of the commercially-available systems utilize liquid reagents and require analyzer equipment having intricate solution handling and transport capabilities. Recent developments, however, have provided test elements in essentially planar, dry form which can be loaded into a cartridge for use in an analyzer. In the use of such an analyzer, a test element from a cartridge is fed into a metering station where a predetermined amount of sample fluid is deposited on the test element. After an incubation period, the element is mo~ed to a read station where a change in the test element is measured, the amount of change being proportional to a particular analyte in the fluid.
The test element is used only once and is discarded after the reading has been taken. An analyzer for use with such test elements is disclosed in commonly-assigned U.S. Pat. ~o. 4,152,390.
- ~ - . . . .
~ 8 ~ 4 Test elements of the type described above sre adapted to function with very small quantities of sample fluido For example, test elements for performing colorimetric analyses can produce a 5 measurable response with only 10 microliters of sample fluid, and elements for performing potentiometric analyses are operable with 10 microliters of sample fluid and 10 microliters of reference fluid. The volume of fluid supplied to 10 the elements should preferably not vary more than 5%
from a selected value to achieve desirable test results. Thus, there is a problem in provi~ing a metering device which can deliver precise micro quantities of fluid, in spite of variations in the 15 physical properties of the fluid and the test ele~lents. Moreover, in high-throughput analyzers, the metering device must be capable of repeatealy and accurately dispensing such quantities of fluid onto the test elements as they are sequentially 20 moved into a metering station.
A metering device for use with planar test elements is shown in commonly-owned U.S. Pat. No.
4,142,656, to Smith et al. In this patent, fluid is dispensed from a sample cup having a dispensing tip 25 formed on a bottom wall thereof. An electrically-actuated pump is used to generate a pressure in the cup sufficiently above ambient to form a pendant drop on the dispensing tip. The test element is then moved into contact with the pendant drop to 30 effect a ~ransfer of the fluid to the element. Both the sample cup and the test element are transported to the metering apparatus. The metering device disclosed in the Smith et al. patent requires complex transport and drive elements for both the 35 sample cup and the test element, and it is not ' ~' .
~5~L899~
intended for use in applications where fluid must be aspirated into the metering device.
The patent to Drozdowski et al., U.S. Pat.
~o. 3,832,135, discloses a metering device which is adapted to pick up a disposable tip, aspirate fluid into the tip, meter fluid into a receptacle, and eject the tip. Drozdowski et al., however, do not contemplate the metering of fluids onto a series of analysis slides. The patent to Lightner, U.S. Pat.
~o. 3,988,921, shows apparatus for metering through a capillary tube onto a chromatographic plate. In the Lightner apparatus, the capillary tube is loaded with a quantity of fluid, and all of the fluid in the tube is dispensed onto a single plate. Since the tube must be reloaded for each new plate, the Lightner apparatus would not be suitable for use in a high-throughput analyzer where a series of tests are performed on a single sample fluid. Further, none of the known prior-art devices is directed to solving the problem of aspirating a fluid from a sample cup and depositing predetermined amounts of the fluid onto a plurality of analysis slides sequentially moved into a metering station.
SUM~RY OF THE INVENTION
-It is an object of the present invention to overcome the above-described problem in prior-art devices, and to provide a novel method and apparatus for the repeated, precise dispensing of micro quantities of fluid onto test elements for the 3 analysis of biological fluids. The invention is particularly applicable to the metering of biological fluids onto generally planar test elements, or analysis slides.
In accordance with one aspect of the invention there is provided meterin~ apparatus for ~;
... . :
g~
precisely dispensing a predetermined quantity of a biological fluid onto a plurality of generally planar analysis slides sequentially moved into a metering station, the slides being selected from more than one type and different types having different rates of absorption, the apparatus comprising: dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into the tip through an aperture therein, the chamber being sufficiently large to contain enough fluid for a plurality of the slides; pump means in fluid communication with the metering tip, the pump means being actuatable for a preselected period to ~xpel fluid from the tip at a substan-tially constant dispense rate; and positioning meansoperatively connected to the dispenser means for moving the tip to a metering position adjacent to a slide in the metering station and spaceà a sufficient distance from the slide such that fluid delivered at the dispense rate will flow in a continuous stream to the slide, the positioning means being adapted to withdraw the tip from the metering position a predetermined time after the period.
There is also disclosed a process for the precise dispensing of a biological fl~id from a metering tip onto a generally planar analysis sliae;
the process comprising the steps of: aspirating the fluid into the tip until the tip is partially filled 3 with fluid and has an air space above the fl~id;
positioning the tip in a metering position closely adjacent the slide and spaced therefrom between about 0.030cm and about 0.15cm; pressurizing the air and fluid in the tip for a preselected period to force about 10 ~1 of fluid onto the slide at a dispense rate of between ab~ut 10 ~l/sec and 300 8~ ~
~1/sec; and maintaining the tip in the metering position between about 0.05 second and about 0.5 second after the period and then withdrawing the tip from the metering position.
In one embodiment of the invention, a dispenser having a disposable metering tip is supported on a carriage which is mounted on support rods for lateral movement. The dispenser is raised and lowered by means of a rack-and-pinion drive. At the start of a metering cycle, the carriage is moved to locate the dispenser over a waste receptacle where the metering tip from the preceding metering cycle is ejected. The dispenser then picks up a new metering tip, and a supply of sample fluid is aspirated into the tip. Ihe dispenser means is then moved to position the tip in a metering position where a predetermined amount of sample fluid is deposited onto an analysis slide to complete the metering cycle.
In the event several different tests are desired on the same sample fluid, the metering tip is raised after each metering operation and lowered into the metering position for each new analysis slide. Cross-contamination fro~ one sample fluid to another is eliminaated, since sample fluid does not pass beyond the metering tip, and each metering tip is used for only one sample fluid.
The disclosed invention is adapted to deliver fluid to a slide with the desired precision and accuracy, in spite of substantial variations in the physical properties of the fluid. To achieve this result, applicants have found that several properties must be carefully controlled, including the spacing of the metering tip from the analysis slide, the rate at which the fluid is expelled from the tip, the dwell time of the metering tip in the ~5~89~l metering position after the pump stops, and the rate ' at which the tip is withdrawn from the slide after completion of the metering operation.
BRIEF D~SCRlPTTO~ OF THE DRAWI~GS
Fig. 1 is a perspective view of a chemical analyzer of the type which is adapted to employ the metering apparatus described herein;
Fig. 2 is a perspective view of the metering apparatus of the subject invention, showing the dispenser and the carriage for the dispenser;
Fig. 3 is a perspective view of a pump for the dispenser and a drive mechanism for the carriage; and Fig. 4 is an enlarged elevational view, partially in section, showing a metering tip in the metering position over an analysis slide.
DESCRIFIION OF THE PREFERR~ ~MBO~IME~I
The invention is described hereinafter in connection with an analyzer for performing quantitative chemical analyses of biological fluids, such as blood serum. However, the invention is not so limited, and it can also be employed in other types of apparatus where precise metering devices are required. Although the dipensing of blood sera is described hereinafter by way of example, the apparatus may be used to dispense fluid in any repetitive dispensing operation which requires that the amount of dispensed fluid be uniform in spite of substantial variation in physical properties of the sample fluid so dispensed.
One form of test element, or analysis slide, for use with the subject invention is disclosed in the commonly-owned U.S. Patent to Pryzbylowicz et al., U.S. Pat. ~o. 3,992,158, granted on November 16, 1976. lhe test element disclosed in this pater,t is formed as a multi-layer ' - . . . . .
~5189 element containing the necessary reagents for reaction with componoents of a biological fluid, such as blood serum, deposited thereon. Certain reactions colorimetrically produce a change in optical density in the element which is sensed by a reflectometer, the amount of light reflected from the element varying in accordance with the reaction and being indicative of the amount of a particular analyte present in the fluid. Another form of test element for use with the disclosed invention is shown in the patent to Hamblen et al., U.S. Pat. ~o.
4,053,381, granted October 11, 1977. This patent describes a test element, or analysis slide, of the type which is used to potentiometrically designate the activity of ions in a liquid test solution by the use of electrodes.
The different forms of test elements usable with applicants' invention will vary to some degree in the absorption rates at which they attract fluid metered onto the element; this is due, in part, to a variance in the capillary action in the different forms of elements and to a wicking action between layers in certain elementsO Because of this vari-ance in the test elements, certain characterist;cs of applicants' invention, described hereinafter, must be carefully controlled to achieve the desired precision and accuracy.
Terms such as "up," "down," "lower,"
"vertical," "horizontal," and "bottom," as used herein, refer to the orientation of parts when the disclosed apparatus is positioned in its customary position of use.
The sera to be dispensed are to be tested by devices requiring very accurate, small volumes of sera. The volumes to be dispensed are substantially fixed for a particular application and range from l 5~ ~ 4 -B-to about 30 microliters, and preferably between about 8 and about 13 microliters. Such small volumes permit the performance of multiple tests on a relatively small volume of serum from a patient;
in the case of elderly or infant patients, only small volumes of blood are available for testing, and the smaller the volume needed for each test, the greater the number of tests which can be run on a given sample of serum.
~0 In accordance with the preferre~ embodiment of the invention, there is shown in Fig. 1 an analyzer 12 of the type which is adapte~ to employ a ~etering apparatus 18, described in detail herein-after. Analyzer 12 comprises a slide supply 14 for analysis slides 15 of the colorimetric type (Fig.
BACKGROU~iD OF THE I~VENTIO~;
lo Field of the Invention This invention relates to the chemical analysis of substances, and more particularly to a method and apparatus for the precise metering of biological fluids onto test elements.
State of the Prior Art A number of automated systems have been aeveloped for performing quantitative chemical analyses of fluid samples. Most of the commercially-available systems utilize liquid reagents and require analyzer equipment having intricate solution handling and transport capabilities. Recent developments, however, have provided test elements in essentially planar, dry form which can be loaded into a cartridge for use in an analyzer. In the use of such an analyzer, a test element from a cartridge is fed into a metering station where a predetermined amount of sample fluid is deposited on the test element. After an incubation period, the element is mo~ed to a read station where a change in the test element is measured, the amount of change being proportional to a particular analyte in the fluid.
The test element is used only once and is discarded after the reading has been taken. An analyzer for use with such test elements is disclosed in commonly-assigned U.S. Pat. ~o. 4,152,390.
- ~ - . . . .
~ 8 ~ 4 Test elements of the type described above sre adapted to function with very small quantities of sample fluido For example, test elements for performing colorimetric analyses can produce a 5 measurable response with only 10 microliters of sample fluid, and elements for performing potentiometric analyses are operable with 10 microliters of sample fluid and 10 microliters of reference fluid. The volume of fluid supplied to 10 the elements should preferably not vary more than 5%
from a selected value to achieve desirable test results. Thus, there is a problem in provi~ing a metering device which can deliver precise micro quantities of fluid, in spite of variations in the 15 physical properties of the fluid and the test ele~lents. Moreover, in high-throughput analyzers, the metering device must be capable of repeatealy and accurately dispensing such quantities of fluid onto the test elements as they are sequentially 20 moved into a metering station.
A metering device for use with planar test elements is shown in commonly-owned U.S. Pat. No.
4,142,656, to Smith et al. In this patent, fluid is dispensed from a sample cup having a dispensing tip 25 formed on a bottom wall thereof. An electrically-actuated pump is used to generate a pressure in the cup sufficiently above ambient to form a pendant drop on the dispensing tip. The test element is then moved into contact with the pendant drop to 30 effect a ~ransfer of the fluid to the element. Both the sample cup and the test element are transported to the metering apparatus. The metering device disclosed in the Smith et al. patent requires complex transport and drive elements for both the 35 sample cup and the test element, and it is not ' ~' .
~5~L899~
intended for use in applications where fluid must be aspirated into the metering device.
The patent to Drozdowski et al., U.S. Pat.
~o. 3,832,135, discloses a metering device which is adapted to pick up a disposable tip, aspirate fluid into the tip, meter fluid into a receptacle, and eject the tip. Drozdowski et al., however, do not contemplate the metering of fluids onto a series of analysis slides. The patent to Lightner, U.S. Pat.
~o. 3,988,921, shows apparatus for metering through a capillary tube onto a chromatographic plate. In the Lightner apparatus, the capillary tube is loaded with a quantity of fluid, and all of the fluid in the tube is dispensed onto a single plate. Since the tube must be reloaded for each new plate, the Lightner apparatus would not be suitable for use in a high-throughput analyzer where a series of tests are performed on a single sample fluid. Further, none of the known prior-art devices is directed to solving the problem of aspirating a fluid from a sample cup and depositing predetermined amounts of the fluid onto a plurality of analysis slides sequentially moved into a metering station.
SUM~RY OF THE INVENTION
-It is an object of the present invention to overcome the above-described problem in prior-art devices, and to provide a novel method and apparatus for the repeated, precise dispensing of micro quantities of fluid onto test elements for the 3 analysis of biological fluids. The invention is particularly applicable to the metering of biological fluids onto generally planar test elements, or analysis slides.
In accordance with one aspect of the invention there is provided meterin~ apparatus for ~;
... . :
g~
precisely dispensing a predetermined quantity of a biological fluid onto a plurality of generally planar analysis slides sequentially moved into a metering station, the slides being selected from more than one type and different types having different rates of absorption, the apparatus comprising: dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into the tip through an aperture therein, the chamber being sufficiently large to contain enough fluid for a plurality of the slides; pump means in fluid communication with the metering tip, the pump means being actuatable for a preselected period to ~xpel fluid from the tip at a substan-tially constant dispense rate; and positioning meansoperatively connected to the dispenser means for moving the tip to a metering position adjacent to a slide in the metering station and spaceà a sufficient distance from the slide such that fluid delivered at the dispense rate will flow in a continuous stream to the slide, the positioning means being adapted to withdraw the tip from the metering position a predetermined time after the period.
There is also disclosed a process for the precise dispensing of a biological fl~id from a metering tip onto a generally planar analysis sliae;
the process comprising the steps of: aspirating the fluid into the tip until the tip is partially filled 3 with fluid and has an air space above the fl~id;
positioning the tip in a metering position closely adjacent the slide and spaced therefrom between about 0.030cm and about 0.15cm; pressurizing the air and fluid in the tip for a preselected period to force about 10 ~1 of fluid onto the slide at a dispense rate of between ab~ut 10 ~l/sec and 300 8~ ~
~1/sec; and maintaining the tip in the metering position between about 0.05 second and about 0.5 second after the period and then withdrawing the tip from the metering position.
In one embodiment of the invention, a dispenser having a disposable metering tip is supported on a carriage which is mounted on support rods for lateral movement. The dispenser is raised and lowered by means of a rack-and-pinion drive. At the start of a metering cycle, the carriage is moved to locate the dispenser over a waste receptacle where the metering tip from the preceding metering cycle is ejected. The dispenser then picks up a new metering tip, and a supply of sample fluid is aspirated into the tip. Ihe dispenser means is then moved to position the tip in a metering position where a predetermined amount of sample fluid is deposited onto an analysis slide to complete the metering cycle.
In the event several different tests are desired on the same sample fluid, the metering tip is raised after each metering operation and lowered into the metering position for each new analysis slide. Cross-contamination fro~ one sample fluid to another is eliminaated, since sample fluid does not pass beyond the metering tip, and each metering tip is used for only one sample fluid.
The disclosed invention is adapted to deliver fluid to a slide with the desired precision and accuracy, in spite of substantial variations in the physical properties of the fluid. To achieve this result, applicants have found that several properties must be carefully controlled, including the spacing of the metering tip from the analysis slide, the rate at which the fluid is expelled from the tip, the dwell time of the metering tip in the ~5~89~l metering position after the pump stops, and the rate ' at which the tip is withdrawn from the slide after completion of the metering operation.
BRIEF D~SCRlPTTO~ OF THE DRAWI~GS
Fig. 1 is a perspective view of a chemical analyzer of the type which is adapted to employ the metering apparatus described herein;
Fig. 2 is a perspective view of the metering apparatus of the subject invention, showing the dispenser and the carriage for the dispenser;
Fig. 3 is a perspective view of a pump for the dispenser and a drive mechanism for the carriage; and Fig. 4 is an enlarged elevational view, partially in section, showing a metering tip in the metering position over an analysis slide.
DESCRIFIION OF THE PREFERR~ ~MBO~IME~I
The invention is described hereinafter in connection with an analyzer for performing quantitative chemical analyses of biological fluids, such as blood serum. However, the invention is not so limited, and it can also be employed in other types of apparatus where precise metering devices are required. Although the dipensing of blood sera is described hereinafter by way of example, the apparatus may be used to dispense fluid in any repetitive dispensing operation which requires that the amount of dispensed fluid be uniform in spite of substantial variation in physical properties of the sample fluid so dispensed.
One form of test element, or analysis slide, for use with the subject invention is disclosed in the commonly-owned U.S. Patent to Pryzbylowicz et al., U.S. Pat. ~o. 3,992,158, granted on November 16, 1976. lhe test element disclosed in this pater,t is formed as a multi-layer ' - . . . . .
~5189 element containing the necessary reagents for reaction with componoents of a biological fluid, such as blood serum, deposited thereon. Certain reactions colorimetrically produce a change in optical density in the element which is sensed by a reflectometer, the amount of light reflected from the element varying in accordance with the reaction and being indicative of the amount of a particular analyte present in the fluid. Another form of test element for use with the disclosed invention is shown in the patent to Hamblen et al., U.S. Pat. ~o.
4,053,381, granted October 11, 1977. This patent describes a test element, or analysis slide, of the type which is used to potentiometrically designate the activity of ions in a liquid test solution by the use of electrodes.
The different forms of test elements usable with applicants' invention will vary to some degree in the absorption rates at which they attract fluid metered onto the element; this is due, in part, to a variance in the capillary action in the different forms of elements and to a wicking action between layers in certain elementsO Because of this vari-ance in the test elements, certain characterist;cs of applicants' invention, described hereinafter, must be carefully controlled to achieve the desired precision and accuracy.
Terms such as "up," "down," "lower,"
"vertical," "horizontal," and "bottom," as used herein, refer to the orientation of parts when the disclosed apparatus is positioned in its customary position of use.
The sera to be dispensed are to be tested by devices requiring very accurate, small volumes of sera. The volumes to be dispensed are substantially fixed for a particular application and range from l 5~ ~ 4 -B-to about 30 microliters, and preferably between about 8 and about 13 microliters. Such small volumes permit the performance of multiple tests on a relatively small volume of serum from a patient;
in the case of elderly or infant patients, only small volumes of blood are available for testing, and the smaller the volume needed for each test, the greater the number of tests which can be run on a given sample of serum.
~0 In accordance with the preferre~ embodiment of the invention, there is shown in Fig. 1 an analyzer 12 of the type which is adapte~ to employ a ~etering apparatus 18, described in detail herein-after. Analyzer 12 comprises a slide supply 14 for analysis slides 15 of the colorimetric type (Fig.
2), and a slide supply 16 for analysis slides of the potentiometric type, not shown. Metering apparatus 18 is adapted to aspirate sample fluid from a cup 1 supported in a sample tray 20 ana to deposit a predetermined amount of the fluid onto an analysls slide supported in a slide distributor 30. A second metering device, not shown, works in conjunction with metering apparatus 30 to also deposit reference fluid on analysis slides of the potentiometric type. After the metering operation, analysis slides of the potentiometric type are deposited in an incubator 22 by distributor 30, and analysis slides of the colorimetric type are deposited in an incubator 24. Incubators 22, 24, are adapted to cooperate respectively with analysis means 23, 25, for measuring a change in the analysis slides as a recult of the fluids deposited thereon.
With reference to Fig. 2, metering apparatus 1~ comprises a dispenser 40 and a means for positioning dispenser 40 which includes a carriage 42 for mo~ing dispenser 4G laterally ; . - . .
~51~394 through a plurality of stations in analyzer 12, and a vertical drive 44 for raisin~ and lowering dispenser 40 at each of the stations. Dispenser 40 comprises a dispenser head 46 which is adapted to receive a disposable metering tip 48, and is connected by means of a line 50 to a pump 52 (Fig.
With reference to Fig. 2, metering apparatus 1~ comprises a dispenser 40 and a means for positioning dispenser 40 which includes a carriage 42 for mo~ing dispenser 4G laterally ; . - . .
~51~394 through a plurality of stations in analyzer 12, and a vertical drive 44 for raisin~ and lowering dispenser 40 at each of the stations. Dispenser 40 comprises a dispenser head 46 which is adapted to receive a disposable metering tip 48, and is connected by means of a line 50 to a pump 52 (Fig.
3) of the positive displacement type. ~ump 52 comprises a piston, not shown, which is driven by a bidirectional stepper motor 54.
When motor 54 is actuated in one direction, a partial vacuum is created in line 50 by pump 52, and fluid is drawn into tip 4~ until the tip is partially filled. Motor 54 is actuated in an opposite direction to meter fluid from tip 48. In the metering operation, motor 54 drives pump 52 for a prese]ected period during which the pressure in line 50 and tip 4~ is raised sufficiently to force about lO ~1 of flui~ onto an analysis slide. Under certain operating conditions, depending on the amount of fluid aspirated into tip 48, it may be desirable to vent line 50 before dispensing fluid onto an analysis slide. A pressure transducer 56 closely monitors pressure in line 50 for purposes which will be explained in more detail hereinafter.
Sample tray 20 is adapted to carry a disposable tip 48 for each of the sample fluids to be analyzed. A new tip 48 is used with each sample fluid to avoid any cross-contamination problems.
The cups lg containing sample fluid are arranged around the outer periphery of tray 20, as shown in Fig. 2. An indexing mechanism, not shown, advances tray 20 at the start of each metering cycle to bring a cup 19 and new tip 48 resp~ctively into th~
aspiration station and the tip supply station for 3~ cooperation with metering apparatus 18. Iips 4& can be formed by known molding techniques from polymers, .', . . :
.
,: .
~5~9~L
such as acetal and polypropylene. One tip which is particularly suitable for use in apparatus 18 is the tip described and claimed in commonly-owned Cdn.
Application Ser. No. 362,694 filed on Oct. 17/
1980, by R. L. Columbus, entitled "Self Cleaning ~ozzle Construction for Aspirators." Also, certain commercially-available pipe~te tips have metering characteristics which are acceptable for use in apparatus 18. One example of such a tip is the Elkay #OO0-000-ClC tip, manufactured by Elkay Products, Inc., Worcester, Mass.
Ca-riage 42 is mounted for horizontal movement on two parallel support rods 70. ~ods 70 are carried on a pylon 43 attached to the analyzer frame, not shown. A drive meanc for carriage 42 includes a bidirectional stepper motor 72 (Fig. 3) which is connected to a capstan drive 74. ~rive 74 comprises a dru~i 76; a cable 78 carried on drum 76 is supported on guide pulleys 80 and connected to carriage 42. It will be seen from Figs. 2 and 3, that when motor 72 is driven, for example, in a counterclockwise direction, as viewed in ~ig. 3, carriage 42 will move to the right (Fig. 2).
Carriage 42 must be located along a line at four points which include the tip pick-up station, the aspiration station, the metering station and the tip-eject station. Four horizontal-position sensors 86 of a photoelectric type cooperate h~ith a flag 87 on carriage 42 to precisely position the carriage 42 at each of these stations.
Vertical drive 44 comprises a rack 90 which is attached to dispenser head 46. Rack 90 is raised and lowered by means of a pinion 52 driven by a stepper motor ~4 mounted on carriage 42. Four ~ertical-position sensors 5~ cooperate ~ith a flag 98 on rack 9~ to precisely determine the vertical ~5~894 position of dispenser head 4~. Power from a power supply, not shown, is supplied to the sensors 96 and motor 94 through a ribbon cable 100.
ln the operation of metering apparatus 18, dispenser 40 is moved through at least one complete metering cycle for each sample fluid. At the start of the metering cycle, carriage 42 is moved to the tip-eject station to position dispenser 40 over a waste receptacle 110 where a metering tip 48 from a previous metering cycle is ejected into the receptacle 110 by an ejector, not shown, on head 46. Carriage 42 is then moved by motor 72 to the tip-supply station where dispenser 40 is located directly over a disposable tip 48 in sample tray 20. Dispenser 40 is then lowered to pick up a tip 48, raised, and moved laterally to the aspiration station. ~ispenser 40 is then lowered to locate a tip 48 in a sample cup 19 where it aspirates sufficient sample fluid to perform the number of tests desired. After aspiration and before withdrawal of the tip 48, approximately 10 ~1 of fluid are dispensed back into cup 19; this primes the dispenser and insures that the first analysis slide will receive a precise amount of fluid. The dispenser 40 is then raised, moved laterally to the metering station where tip 48 is positioned directly over an analysis slide 15; tip 48 is then lowered into a guide 116 ~Fig. 2) on distributor 30 which locates the tip 48 in the metering position. Pump 52 is then actuated for a preselected period to meter the desired amount of sample fluid onto the analysis slide 15. ~ip 48 remains in the metering position for a predetermined time after pump 52 stops to complete the metering operation; then dispenser 40 is raised to a home position, shown in Fig. 2. In most cases, more than one analysis will 39~
be performed per sample fluid. If additional analyses are being performed, the dispenser 40 will be raised and lowered for each new slide.
~letering apparatus 13 is particularly suitable for use with biological fluids, e.g. blood serum having a surface tension which varies between about 28 dynes/c~ and about 75 dynes/cm and a relative viscosity between about 0.8 and about 3 (compared to distilled water). Apparatus 18 is 10 adapted to dispense these fluids such that the mean metered volume does not vary more than 5% from a selected value, and the precision, expressed as a coefficient of variation, is less than 5%. To achieve these results, metering apparatus preferably 15 has the properties listed below.
1. There should be no separation of the fluid stream during the metering operation. Io make sure that separation does not occur it has been found that the spacing ~ of tip 48 from slide 15 20 (See ~ig. 4) i~ preferably between about 0.012 inches (0.030cm) and about 0.060 inches (0.15cm).
2. It is also preferred that the dispense rate at which fluid is expelled from tip 48 is between about 10 ~l/sec and about 3Q0 ~l/sec. If 25 the dispense rate is too slow, there is danger of separation of the fluid stream, even with proper spacing of tip 48 fro~ slide 15; if the rate is too fast, fluid tends to build up around tip 48. A
representative rate within this range is 50 ~l/sec, 30 which can be used regardless of the type or chemistry of the slide onto which the fluid is being metered. That is, this fixed, predetermined rate has been used both on colorimetric type slides, eOg.
glucose, ~U~, or a like assay, as well as on 35 potentiometric slides, e.g. a NA assay.
3. At the completion of the cispensing of ~ ~5~ ~94 .
fluid, i.e. after pump 52 has stopped, it is preferred that tip 48 dwell in the metering position (Fig. 4) between about 0.05 sec and about 0.5 second before being withdrawn. This insures that there will be a clean break of the stream of fluid upon withdrawal; if the tip dwells for a greater period of time, fluid may be pulled out o~ tip 48 by the slide.
When motor 54 is actuated in one direction, a partial vacuum is created in line 50 by pump 52, and fluid is drawn into tip 4~ until the tip is partially filled. Motor 54 is actuated in an opposite direction to meter fluid from tip 48. In the metering operation, motor 54 drives pump 52 for a prese]ected period during which the pressure in line 50 and tip 4~ is raised sufficiently to force about lO ~1 of flui~ onto an analysis slide. Under certain operating conditions, depending on the amount of fluid aspirated into tip 48, it may be desirable to vent line 50 before dispensing fluid onto an analysis slide. A pressure transducer 56 closely monitors pressure in line 50 for purposes which will be explained in more detail hereinafter.
Sample tray 20 is adapted to carry a disposable tip 48 for each of the sample fluids to be analyzed. A new tip 48 is used with each sample fluid to avoid any cross-contamination problems.
The cups lg containing sample fluid are arranged around the outer periphery of tray 20, as shown in Fig. 2. An indexing mechanism, not shown, advances tray 20 at the start of each metering cycle to bring a cup 19 and new tip 48 resp~ctively into th~
aspiration station and the tip supply station for 3~ cooperation with metering apparatus 18. Iips 4& can be formed by known molding techniques from polymers, .', . . :
.
,: .
~5~9~L
such as acetal and polypropylene. One tip which is particularly suitable for use in apparatus 18 is the tip described and claimed in commonly-owned Cdn.
Application Ser. No. 362,694 filed on Oct. 17/
1980, by R. L. Columbus, entitled "Self Cleaning ~ozzle Construction for Aspirators." Also, certain commercially-available pipe~te tips have metering characteristics which are acceptable for use in apparatus 18. One example of such a tip is the Elkay #OO0-000-ClC tip, manufactured by Elkay Products, Inc., Worcester, Mass.
Ca-riage 42 is mounted for horizontal movement on two parallel support rods 70. ~ods 70 are carried on a pylon 43 attached to the analyzer frame, not shown. A drive meanc for carriage 42 includes a bidirectional stepper motor 72 (Fig. 3) which is connected to a capstan drive 74. ~rive 74 comprises a dru~i 76; a cable 78 carried on drum 76 is supported on guide pulleys 80 and connected to carriage 42. It will be seen from Figs. 2 and 3, that when motor 72 is driven, for example, in a counterclockwise direction, as viewed in ~ig. 3, carriage 42 will move to the right (Fig. 2).
Carriage 42 must be located along a line at four points which include the tip pick-up station, the aspiration station, the metering station and the tip-eject station. Four horizontal-position sensors 86 of a photoelectric type cooperate h~ith a flag 87 on carriage 42 to precisely position the carriage 42 at each of these stations.
Vertical drive 44 comprises a rack 90 which is attached to dispenser head 46. Rack 90 is raised and lowered by means of a pinion 52 driven by a stepper motor ~4 mounted on carriage 42. Four ~ertical-position sensors 5~ cooperate ~ith a flag 98 on rack 9~ to precisely determine the vertical ~5~894 position of dispenser head 4~. Power from a power supply, not shown, is supplied to the sensors 96 and motor 94 through a ribbon cable 100.
ln the operation of metering apparatus 18, dispenser 40 is moved through at least one complete metering cycle for each sample fluid. At the start of the metering cycle, carriage 42 is moved to the tip-eject station to position dispenser 40 over a waste receptacle 110 where a metering tip 48 from a previous metering cycle is ejected into the receptacle 110 by an ejector, not shown, on head 46. Carriage 42 is then moved by motor 72 to the tip-supply station where dispenser 40 is located directly over a disposable tip 48 in sample tray 20. Dispenser 40 is then lowered to pick up a tip 48, raised, and moved laterally to the aspiration station. ~ispenser 40 is then lowered to locate a tip 48 in a sample cup 19 where it aspirates sufficient sample fluid to perform the number of tests desired. After aspiration and before withdrawal of the tip 48, approximately 10 ~1 of fluid are dispensed back into cup 19; this primes the dispenser and insures that the first analysis slide will receive a precise amount of fluid. The dispenser 40 is then raised, moved laterally to the metering station where tip 48 is positioned directly over an analysis slide 15; tip 48 is then lowered into a guide 116 ~Fig. 2) on distributor 30 which locates the tip 48 in the metering position. Pump 52 is then actuated for a preselected period to meter the desired amount of sample fluid onto the analysis slide 15. ~ip 48 remains in the metering position for a predetermined time after pump 52 stops to complete the metering operation; then dispenser 40 is raised to a home position, shown in Fig. 2. In most cases, more than one analysis will 39~
be performed per sample fluid. If additional analyses are being performed, the dispenser 40 will be raised and lowered for each new slide.
~letering apparatus 13 is particularly suitable for use with biological fluids, e.g. blood serum having a surface tension which varies between about 28 dynes/c~ and about 75 dynes/cm and a relative viscosity between about 0.8 and about 3 (compared to distilled water). Apparatus 18 is 10 adapted to dispense these fluids such that the mean metered volume does not vary more than 5% from a selected value, and the precision, expressed as a coefficient of variation, is less than 5%. To achieve these results, metering apparatus preferably 15 has the properties listed below.
1. There should be no separation of the fluid stream during the metering operation. Io make sure that separation does not occur it has been found that the spacing ~ of tip 48 from slide 15 20 (See ~ig. 4) i~ preferably between about 0.012 inches (0.030cm) and about 0.060 inches (0.15cm).
2. It is also preferred that the dispense rate at which fluid is expelled from tip 48 is between about 10 ~l/sec and about 3Q0 ~l/sec. If 25 the dispense rate is too slow, there is danger of separation of the fluid stream, even with proper spacing of tip 48 fro~ slide 15; if the rate is too fast, fluid tends to build up around tip 48. A
representative rate within this range is 50 ~l/sec, 30 which can be used regardless of the type or chemistry of the slide onto which the fluid is being metered. That is, this fixed, predetermined rate has been used both on colorimetric type slides, eOg.
glucose, ~U~, or a like assay, as well as on 35 potentiometric slides, e.g. a NA assay.
3. At the completion of the cispensing of ~ ~5~ ~94 .
fluid, i.e. after pump 52 has stopped, it is preferred that tip 48 dwell in the metering position (Fig. 4) between about 0.05 sec and about 0.5 second before being withdrawn. This insures that there will be a clean break of the stream of fluid upon withdrawal; if the tip dwells for a greater period of time, fluid may be pulled out o~ tip 48 by the slide.
4. After the dwell time as noted above, it is preferred that tip 48 be withdrawn from the - metering position at a rate of between about 0.2 inches/sec (0.5cm/sec) and about 2 inches/sec ~5.08cm/sec). The tip 48 is withdrawn at a relatively slow rate to allow a fluid wipe-off effect.
In the use of the disclosed metering apparatus with a high-throughput analyzer, as shown in Fig. 1, a metering operation takes place approximately every 12 seconds. Ihus, it will be seen that each of the steps in the metering cycle must be carefully controlled and monitored, and metering apparatus 18 must function in timed relation to other elements of analyzer 12. Pressure transducer 56 is used to monitor the performance of apparatus 18. Fressure is sensed in line 50, and if conditions are present such as a plugged tip 48, no fluid in cup 19, or a separation of the fluid stream between the tip 48 and the slide 15, they will be detected by the transducer. A control system (not shown~ for metering apparatus 18 could include one or more computers which may take any of the various forms known in the art that include programmable microcomputers. The instructions and method of programming such computers is well known in the art, and thus, no further explanation is considered necessary.
~ ~ 5~ ~9 ~
The inven~ion has been described in detail with reference to certain preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
In the use of the disclosed metering apparatus with a high-throughput analyzer, as shown in Fig. 1, a metering operation takes place approximately every 12 seconds. Ihus, it will be seen that each of the steps in the metering cycle must be carefully controlled and monitored, and metering apparatus 18 must function in timed relation to other elements of analyzer 12. Pressure transducer 56 is used to monitor the performance of apparatus 18. Fressure is sensed in line 50, and if conditions are present such as a plugged tip 48, no fluid in cup 19, or a separation of the fluid stream between the tip 48 and the slide 15, they will be detected by the transducer. A control system (not shown~ for metering apparatus 18 could include one or more computers which may take any of the various forms known in the art that include programmable microcomputers. The instructions and method of programming such computers is well known in the art, and thus, no further explanation is considered necessary.
~ ~ 5~ ~9 ~
The inven~ion has been described in detail with reference to certain preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention.
Claims (14)
1. Metering apparatus for precisely dispensing a predetermined quantity of a biological fluid onto a plurality of generally planar analysis slides sequentially moved into a metering station, said slides being selected from more than one type and different types having different rates of absorption, said apparatus comprising:
dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into the tip through an aperture therein, said chamber being sufficiently large to contain enough fluid for a plurality of said slides;
pump means in fluid communication with said metering tip, said pump means being actuatable for a preselected period to expel fluid from said tip at a substantially constant dispense rate; and positioning means operatively connected to said dispenser means for moving said tip to a metering position adjacent to a slide in the metering station and spaced a sufficient distance from the slide such that fluid delivered at said dispense rate will flow in a continuous stream to said slide, said positioning means being adapted to withdraw said tip from said metering position a predetermined time after said period.
dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into the tip through an aperture therein, said chamber being sufficiently large to contain enough fluid for a plurality of said slides;
pump means in fluid communication with said metering tip, said pump means being actuatable for a preselected period to expel fluid from said tip at a substantially constant dispense rate; and positioning means operatively connected to said dispenser means for moving said tip to a metering position adjacent to a slide in the metering station and spaced a sufficient distance from the slide such that fluid delivered at said dispense rate will flow in a continuous stream to said slide, said positioning means being adapted to withdraw said tip from said metering position a predetermined time after said period.
2. Metering apparatus, as defined in Claim 1, wherein said dispense rate is between about 10 µl/sec and about 300 µl/sec.
3. Metering apparatus, as defined in Claim l, wherein said distance is between about 0.030cm and about 0.15cm.
4. Metering apparatus, as defined in Claim 1, wherein said time is between about 0.05 second and about 0.5 second.
5. Metering apparatus, as defined in Claim 1, wherein said positioning means is adapted to withdraw said tip at a rate of between about 0.5 cm/sec and about 5.08 cm/sec.
6. Metering apparatus, as defined in Claim 1, wherein said quantity of fluid is about 10 µl.
7. Metering apparatus, as defined in Claim 1, wherein said fluid has a surface tension within the range from between about 28 dynes/cm to about 75 dynes/cm.
8. A process for the precise dispensing of a biological fluid from a metering tip onto a generally planar analysis slide, said process comprising the steps of:
aspirating the fluid into said tip until the tip is partially filled with fluid and has an air space above the fluid;
positioning the tip in a metering position closely adjacent the slide and spaced therefrom between about 0.030 cm and about 0.15 cm;
pressurizing the air and fluid in the tip for a preselected period to force about 10 µl of fluid onto the slide at a fixed, predetermined dispense rate of between about 10 µl/sec and 300 µl/sec; and maintaining said tip in the metering position between about 0.05 second and about 0.5 second after said period and then withdrawing the tip from said metering position.
aspirating the fluid into said tip until the tip is partially filled with fluid and has an air space above the fluid;
positioning the tip in a metering position closely adjacent the slide and spaced therefrom between about 0.030 cm and about 0.15 cm;
pressurizing the air and fluid in the tip for a preselected period to force about 10 µl of fluid onto the slide at a fixed, predetermined dispense rate of between about 10 µl/sec and 300 µl/sec; and maintaining said tip in the metering position between about 0.05 second and about 0.5 second after said period and then withdrawing the tip from said metering position.
9. A process, as defined in Claim 8, wherein said tip is withdrawn from the metering position at the rate of between about 0.5 cm/sec and about 5.08 cm/sec.
10. Metering apparatus for use in an analyzer for the analysis of biological fluids, said apparatus being adapted to meter a predetermined quantity of fluid onto an analysis slide for the testing of a particular analyte, said analyzer being adapted to measure a change in said slide which is indicative of the amount of analyte in said fluid, said apparatus comprising:
means for supporting said slide in a metering station;
dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into said tip through an aperture therein;
pump means in fluid communication with said metering tip; said pump means being adapted to aspirate fluid into said tip and to expel fluid therefrom in precise amounts;
carriage means for moving said dispenser means laterally through a plurality of stations in the analyzer; and drive means for raising and lowering said dispenser means at each of said stations, said drive means being adapted to move said dispenser means independently of said carriage means.
means for supporting said slide in a metering station;
dispenser means including a metering tip having a fluid chamber for receiving fluid aspirated into said tip through an aperture therein;
pump means in fluid communication with said metering tip; said pump means being adapted to aspirate fluid into said tip and to expel fluid therefrom in precise amounts;
carriage means for moving said dispenser means laterally through a plurality of stations in the analyzer; and drive means for raising and lowering said dispenser means at each of said stations, said drive means being adapted to move said dispenser means independently of said carriage means.
11. Metering apparatus, as defined in Claim 10, wherein said dispenser means comprises a dispenser head for receiving said tip and a pressure detecting means in fluid communication with said tip is connected to said dispenser head.
12. Metering apparatus, as defined in Claim 10, wherein said pump means comprises a positive displacement pump and a stepper motor connected to said pump.
13. Metering apparatus, as defined in Claim 10, wherein said carriage means comprises a carriage movably supported on generally parallel support rods, and a capstan drive connected to said carriage.
14. Metering apparatus, as defined in Claim 10, wherein said drive means comprises a rack and pinion operatively connected to said dispenser means.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15956380A | 1980-06-16 | 1980-06-16 | |
US159,563 | 1980-06-16 | ||
US260,855 | 1981-05-06 | ||
US06/260,855 US4340390A (en) | 1980-06-16 | 1981-05-06 | Method and apparatus for metering biological fluids |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1151894A true CA1151894A (en) | 1983-08-16 |
Family
ID=26856081
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000377890A Expired CA1151894A (en) | 1980-06-16 | 1981-05-20 | Method and apparatus for metering biological fluids |
Country Status (2)
Country | Link |
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US (1) | US4340390A (en) |
CA (1) | CA1151894A (en) |
Families Citing this family (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4452899A (en) * | 1982-06-10 | 1984-06-05 | Eastman Kodak Company | Method for metering biological fluids |
US4555957A (en) * | 1983-10-14 | 1985-12-03 | Cetus Corporation | Bi-directional liquid sample handling system |
US4539855A (en) * | 1984-05-03 | 1985-09-10 | Eastman Kodak Company | Apparatus for transferring liquid out of a capped container, and analyzer utilizing same |
US4794085A (en) * | 1984-07-19 | 1988-12-27 | Eastman Kodak Company | Apparatus and method for detecting liquid penetration by a container used for aspirating and dispensing the liquid |
FR2571147B1 (en) * | 1984-10-01 | 1986-11-14 | Commissariat Energie Atomique | PROGRAMMABLE AUTOMATON FOR DEPOSITING IN A PRECISE POSITION ON AN ANALYSIS MEDIUM OF A TINY PRECISE QUANTITY OF LIQUID |
JPS61198041A (en) * | 1985-02-28 | 1986-09-02 | Konishiroku Photo Ind Co Ltd | Biochemical-analyzing instrument |
US4675301A (en) * | 1985-04-01 | 1987-06-23 | Eastman Kodak Company | Method for correcting for changes in air pressure above a liquid to be dispensed from a container mounted on a probe |
US4615360A (en) * | 1985-09-05 | 1986-10-07 | Eastman Kodak Company | Means providing separation of exterior sheath of liquid on dispensing tip |
US4647419A (en) * | 1985-10-10 | 1987-03-03 | Eastman Kodak Company | Method and apparatus for producing a flash free pipette |
US5204268A (en) * | 1988-06-02 | 1993-04-20 | Fuji Photo Film Co., Ltd. | Method and apparatus for applying liquid samples |
US4951512A (en) * | 1988-06-23 | 1990-08-28 | Baxter International Inc. | System for providing access to sealed containers |
US5413000A (en) * | 1988-06-23 | 1995-05-09 | Dade International Inc. | Assembly for removing waste from closed sample containers |
US5315887A (en) * | 1988-06-23 | 1994-05-31 | Baxter Diagnostics Inc. | Multiport equalization probe |
US5213761A (en) * | 1989-04-12 | 1993-05-25 | Olympus Optical Co., Ltd. | Automatic chemical analyzer having an improved delivery mechanism |
US5264182A (en) * | 1989-04-12 | 1993-11-23 | Olympus Optical Co., Ltd. | Sample and reagent delivery device with a probe and probe supporting member for preventing contamination |
JP2539512B2 (en) * | 1989-07-17 | 1996-10-02 | 株式会社日立製作所 | Multi-item analyzer and method for operating the analyzer |
US5089229A (en) * | 1989-11-22 | 1992-02-18 | Vettest S.A. | Chemical analyzer |
US5250262A (en) * | 1989-11-22 | 1993-10-05 | Vettest S.A. | Chemical analyzer |
US5010930A (en) * | 1989-12-22 | 1991-04-30 | Eastman Kodak Company | Pipette and liquid transfer apparatus for dispensing liquid for analysis |
AU639575B2 (en) * | 1990-05-01 | 1993-07-29 | Enprotech Corporation | Integral biomolecule preparation device |
EP0465691A1 (en) * | 1990-07-09 | 1992-01-15 | Hewlett-Packard GmbH | Apparatus for processing liquids |
US5143849A (en) * | 1991-03-21 | 1992-09-01 | Eastman Kodak Company | Tip to surface spacing for optimum dispensing controlled by a detected pressure change in the tip |
US6849462B1 (en) | 1991-11-22 | 2005-02-01 | Affymetrix, Inc. | Combinatorial strategies for polymer synthesis |
US6943034B1 (en) | 1991-11-22 | 2005-09-13 | Affymetrix, Inc. | Combinatorial strategies for polymer synthesis |
JP3049615B2 (en) * | 1992-06-08 | 2000-06-05 | ベーリング ダイアグノスティックス,インコーポレーテッド | Liquid dispensing system |
DE69312839T2 (en) * | 1992-09-30 | 1998-01-22 | Johnson & Johnson Clin Diag | Aspirating pipettes |
US5344610A (en) * | 1993-02-03 | 1994-09-06 | Eastman Kodak Company | Aspirator probe with long pivot arm to minimize tip flick |
JP3310380B2 (en) * | 1993-05-10 | 2002-08-05 | オリンパス光学工業株式会社 | Dispensing device |
US5895761A (en) * | 1993-07-21 | 1999-04-20 | Clinical Diagnostic Systems, Inc. | Surface area liquid transfer method and related apparatus |
JP3420824B2 (en) * | 1994-04-15 | 2003-06-30 | 富士写真フイルム株式会社 | Method and apparatus for spotting sample liquid on dry analytical film piece |
US7323298B1 (en) | 1994-06-17 | 2008-01-29 | The Board Of Trustees Of The Leland Stanford Junior University | Microarray for determining the relative abundances of polynuceotide sequences |
US7625697B2 (en) | 1994-06-17 | 2009-12-01 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for constructing subarrays and subarrays made thereby |
JP3571092B2 (en) * | 1994-12-20 | 2004-09-29 | 富士写真フイルム株式会社 | Sample solution spotting method on dry analytical film piece |
US5811306A (en) * | 1995-09-04 | 1998-09-22 | Fuji Photo Film Co., Ltd. | Liquid spotting method |
US5723795A (en) * | 1995-12-14 | 1998-03-03 | Abbott Laboratories | Fluid handler and method of handling a fluid |
US5965828A (en) * | 1995-12-14 | 1999-10-12 | Abbott Laboratories | Fluid handler and method of handling a fluid |
US5915282A (en) * | 1995-12-14 | 1999-06-22 | Abbott Laboratories | Fluid handler and method of handling a fluid |
CA2231305C (en) * | 1997-03-11 | 2007-03-20 | Merrit Nyles Jacobs | Improved analyzer throughput featuring through-the-tip analysis |
US6269846B1 (en) | 1998-01-13 | 2001-08-07 | Genetic Microsystems, Inc. | Depositing fluid specimens on substrates, resulting ordered arrays, techniques for deposition of arrays |
US6428752B1 (en) | 1998-05-14 | 2002-08-06 | Affymetrix, Inc. | Cleaning deposit devices that form microarrays and the like |
US6407858B1 (en) | 1998-05-14 | 2002-06-18 | Genetic Microsystems, Inc | Focusing of microscopes and reading of microarrays |
US6722395B2 (en) * | 1998-01-13 | 2004-04-20 | James W. Overbeck | Depositing fluid specimens on substrates, resulting ordered arrays, techniques for analysis of deposited arrays |
US7095032B2 (en) * | 1998-03-20 | 2006-08-22 | Montagu Jean I | Focusing of microscopes and reading of microarrays |
ATE363339T1 (en) * | 1998-05-01 | 2007-06-15 | Gen Probe Inc | STIRRING DEVICE FOR THE FLUID CONTENTS OF A CONTAINER |
JP3816696B2 (en) * | 1999-06-25 | 2006-08-30 | 株式会社小糸製作所 | Mercury supply method and apparatus for arc tube for discharge lamp |
US6709872B1 (en) * | 2000-05-02 | 2004-03-23 | Irm Llc | Method and apparatus for dispensing low nanoliter volumes of liquid while minimizing waste |
US6797518B1 (en) * | 2000-09-11 | 2004-09-28 | Ortho-Clinical Diagnostics, Inc. | Analysis method with sample quality measurement |
US20020098116A1 (en) * | 2000-12-13 | 2002-07-25 | Fuji Photo Film Co., Ltd. | Biochemical analysis system, and biochemical analysis element cartridge |
US7402282B2 (en) * | 2001-07-20 | 2008-07-22 | Ortho-Clinical Diagnostics, Inc. | Auxiliary sample supply for a clinical analyzer |
US6937955B2 (en) | 2002-03-29 | 2005-08-30 | Ortho-Clinical Diagnostics, Inc. | Method for automatic alignment of metering system for a clinical analyzer |
WO2003097808A2 (en) * | 2002-05-17 | 2003-11-27 | Becton, Dickinson And Company | Automated system for isolating, amplyifying and detecting a target nucleic acid sequence |
US20060246593A1 (en) * | 2003-01-03 | 2006-11-02 | Towler Gavin P | Material processing apparatus and method |
US7517494B2 (en) * | 2003-04-30 | 2009-04-14 | Hewlett-Packard Development Company, L.P. | Test tray and test system for determining response of a biological sample |
US7273591B2 (en) | 2003-08-12 | 2007-09-25 | Idexx Laboratories, Inc. | Slide cartridge and reagent test slides for use with a chemical analyzer, and chemical analyzer for same |
US7396512B2 (en) | 2003-11-04 | 2008-07-08 | Drummond Scientific Company | Automatic precision non-contact open-loop fluid dispensing |
US7588733B2 (en) | 2003-12-04 | 2009-09-15 | Idexx Laboratories, Inc. | Retaining clip for reagent test slides |
DE202006010293U1 (en) * | 2005-07-22 | 2006-08-31 | Tecan Trading Ag | Pipetting device with computer program product for accepting or discarding pipetted liquid samples |
WO2008140742A1 (en) | 2007-05-08 | 2008-11-20 | Idexx Laboratories, Inc. | Chemical analyzer |
WO2010078177A1 (en) * | 2008-12-31 | 2010-07-08 | Ventana Medical Systems, Inc. | Robotic pipette system |
US9797916B2 (en) | 2014-01-10 | 2017-10-24 | Idexx Laboratories, Inc. | Chemical analyzer |
WO2017049363A1 (en) * | 2015-09-23 | 2017-03-30 | Venipoc Pty Ltd | Volumetric dispensing of blood |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3261668A (en) * | 1962-08-14 | 1966-07-19 | Scientific Industries | Chemical analyzer tape |
US3219416A (en) * | 1962-10-30 | 1965-11-23 | Scientific Industries | Apparatus for the automatic chemical sequential treatment and analysis of small quantities of material |
GB1218402A (en) * | 1968-02-13 | 1971-01-06 | Baird & Tatlock Ltd | Improvements relating to a multiple pipetting apparatus |
US3570555A (en) * | 1968-11-12 | 1971-03-16 | Warren E Gilson | Fraction collector |
US3687632A (en) * | 1969-07-30 | 1972-08-29 | Rohe Scientific Corp | System for transferring liquids between containers |
US3739821A (en) * | 1971-04-26 | 1973-06-19 | Technicon Instr | Machine-transferrable pipette |
US4046511A (en) * | 1975-06-16 | 1977-09-06 | Union Carbide Corporation | Pipettor apparatus |
US4004883A (en) * | 1975-07-11 | 1977-01-25 | G. D. Searle & Co. | Sensing, leveling and mixing apparatus |
US3991627A (en) * | 1975-11-28 | 1976-11-16 | Block Engineering, Inc. | Alignment device for sample containers |
DE2642777A1 (en) * | 1976-09-23 | 1978-03-30 | Camag Chemie | DEVICE FOR APPLYING LIQUID SAMPLES TO SURFACES |
SE7614077L (en) * | 1976-12-14 | 1978-06-15 | Pharmacia Fine Chemicals Ab | PROGRAMMABLE FRACTION COLLECTOR |
US4257862A (en) * | 1978-07-24 | 1981-03-24 | Eastman Kodak Company | Chemical analyzer |
US4269803A (en) * | 1979-07-02 | 1981-05-26 | Eastman Kodak Company | Slide transfer mechanism |
-
1981
- 1981-05-06 US US06/260,855 patent/US4340390A/en not_active Expired - Lifetime
- 1981-05-20 CA CA000377890A patent/CA1151894A/en not_active Expired
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US4340390A (en) | 1982-07-20 |
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