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WO1999006149A1 - Instruments de pipetage preremplis avec des echantillons temoins etalonnes - Google Patents

Instruments de pipetage preremplis avec des echantillons temoins etalonnes Download PDF

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Publication number
WO1999006149A1
WO1999006149A1 PCT/US1998/016137 US9816137W WO9906149A1 WO 1999006149 A1 WO1999006149 A1 WO 1999006149A1 US 9816137 W US9816137 W US 9816137W WO 9906149 A1 WO9906149 A1 WO 9906149A1
Authority
WO
WIPO (PCT)
Prior art keywords
analyte
tip
liquid
reservoir
conduit
Prior art date
Application number
PCT/US1998/016137
Other languages
English (en)
Inventor
Stephen F. Mauro
Robert A. Reynolds
Original Assignee
Aalto Scientific, Ltd.
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 Aalto Scientific, Ltd. filed Critical Aalto Scientific, Ltd.
Priority to AU20349/99A priority Critical patent/AU2034999A/en
Publication of WO1999006149A1 publication Critical patent/WO1999006149A1/fr

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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
    • B01L3/0275—Interchangeable or disposable dispensing tips
    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • 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
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • 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
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N2001/2893—Preparing calibration standards
    • 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
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1055—General features of the devices using the transfer device for another function for immobilising reagents, e.g. dried reagents
    • 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
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • G01N35/00693—Calibration

Definitions

  • the invention herein relates to pipettes and pipetting equipment and instruments. More particularly, it relates to such devices which are used to collect, store and dispense reference materials for use as primary/secondary standards, calibrators or quality controls in medical, biological and chemical tests. Description of the Prior Art:
  • reference materials are made up in quantity by dissolving a sample of the reference analyte in a volume of the desired solvent liquid.
  • Analytes are usually provided in solid dehydrated or preferably lyophilized form, since in such forms the analytes, most of which are organic and biological materials, have stable extended shelf lives.
  • the laboratory conventionally mixes a sufficient quantity of solution to enable drawings of reference samples for as long a period as the solution remains effective (which may be from several hours to several weeks). This conventional practice, however, has several drawbacks and allows for the introduction of several different types of error.
  • errors can arise during measuring of the quantity of solid analyte and/or the liquid solvent, during withdrawal of individual sample quantities from the formulated solution, and by partial loss of sample during transport of the reference sample from the solution container to the place at which the analysis is to be run.
  • errors may be random (such as when a laboratory technician misreads the measured weight of the solid analyte or a portion of sample leaks from the test instrument) or systematic (such as when the scale used to weigh the solid analyte is improperly calibrated).
  • the technician works with extreme skill and carefully checks all measurements and equipment frequently, significant errors in standard reference samples can be anticipated.
  • the time demands on laboratory technicians are usually such that there is little time for such thoroughness. Errors therefore consistently creep into reference samples and thus are incorporated into reference and test data.
  • analytes may have extended stability in solid or lyophilized form
  • stability begins to decrease once the analyte is dissolved in the solvent liquid.
  • the master solution properties change, thus often also changing the reference data of the samples. Therefore the laboratory technicians must apply correction factors to the standard samples, depending on when the samples have been drawn from the master solution. Such corrections can introduce additional errors, since the technician may incorrectly calculate or apply the correction, or the correction value itself may be uncertain, since the exact degree of degradation of the master solution normally can only be roughly estimated.
  • the devices of this invention avoid the potentials for error, excessive costs, waste and degradation problems of the prior art, and permit the rapid, consistent, precise and accurate preparation of standard solutions for use as reference samples.
  • An analyte preferably the solute, but also alternatively the solvent
  • which will form the desired test solution is incorporated ("preloaded") in precisely measured amounts into a pipette tip in a form in which it has long term stability.
  • the analyte will initially be in lyophilized form or will be lyophilized in situ within the tip, in which form it can be subsequently readily and quickly dispersed or dissolved in the carrier liquid to form the desired standard or reference solution.
  • analyte forms may be used, such as hydrated analytes, if such are also readily and quickly dispersed or dissolved in the carrier liquid to form the desired standard or reference solution.
  • Use of the preloaded pipette tips and calibrated pipetting devices of this invention permits drawing of accurate predetermined quantities of the carrier liquids into contact with the analyte solids, with the rapid dissolution or dispersion of the analyte in the carrier liquid, thus forming a consistent and accurate reference sample for each individual test.
  • the system is useable for formation of many different standardized reference sample materials and with a variety of different analytical instruments. It substantially eliminates the opportunity for operator error.
  • the reference sample formed by the dissolution or dispersion of the analyte in the carrier liquid is in many cases intended to react with a subsequent experimental, test or calibration material after it is dispensed from the pipette/pipette tip into contact with such material.
  • pipette and "pipette tip” are used herein for convenience and brevity, the devices of this invention will include not only those devices which are conventionally regarded as pipettes or pipette tips, but also all devices which operate in an equivalent manner and have a generally equivalent structure. This may include, but will not be limited to, liquid communication tubing used with an automated sampling instrument.
  • the invention is a pipette tip for creating and dispensing a liquid sample of known properties from a pipetting device having a liquid reservoir of known volume and liquid transfer means cooperating with the reservoir for alternately drawing a defined volume of a carrier liquid into the reservoir from the exterior of the device and dispensing a corresponding volume of the liquid sample to the exterior from the reservoir,
  • tip comprises a tubular liquid conduit attachable to the reservoir and providing liquid communication for the carrier liquid and the liquid sample between the reservoir and the exterior of the device; analyte containment means within the conduit for containing a defined quantity of analyte therein and causing effective contact between the carrier liquid and the analyte during passage of the carrier liquid from the exterior to the reservoir, such that if the analyte is a solute, the solute is rapidly and fully dissolved, dispersed or hydrolyzed in the carrier liquid, or if the analyte is a solvent, the solvent rapidly and fully dissolves or disperses a respective so
  • the invention is capable of operating effectively with the preloaded analyte being either a solute (analyte) or, alternatively, a solvent with the solute being present in the carrier liquid drawn into the tip during use
  • the analyte preloaded into the tip will be the solute or analyte, with the carrier liquid serving as a solvent or suspensant for the analyte
  • the reservoir may be part of a separate pipetting device or similar instrument or it may be a pipette itself and is formed to contain the desired predetermined volume of carrier liquid, with operation of the device precisely and accurately drawing in that specific quantity of carrier liquid desired for dissolution or dispersion of the analyte to form the sample
  • the invention also includes means for retaining a readily available supply of carrier liquid adjacent to detached tips containing preloaded solid analyte, such that when the technician connects the pipette tip to the pipette or instrument, the required quantity of carrier liquid can also obtained and the desired solution sample produced in a single operation
  • the invention is of a pipetting device for collecting and dispensing a standard liquid sample as of a control material, which comprises a liquid reservoir of known volume, liquid transfer means cooperating with the reservoir for alternately drawing a defined volume of a carrier liquid into the reservoir from the exterior of the device and dispensing a corresponding volume of the liquid sample to the exterior from the reservoir, through a pipette tip which comprises a tubular liquid conduit attachable to the reservoir and providing liquid communication for the carrier liquid and the liquid sample between the reservoir and the exterior of the device; analyte containment means within the conduit for containing a defined quantity of analyte therein and causing effective contact between the carrier liquid and the analyte during passage of the carrier liquid from the exterior to the reservoir, such that if the analyte is a solute, the solute is rapidly and fully dissolved, dispersed or hydrolyzed in the carrier liquid, or if the analyte is a solvent, the solvent rapidly and fully dissolves or dispers
  • a container for retaining the detached pipette tips prior to being attached to a pipette or instrument reservoir.
  • the container includes a basin for containing a body of the carrier- liquid and a retainer, such as a rack, for retaining the detached pipette tips disposed above surface level of the body of carrier liquid when the liquid is contained in the basin, the pipette tips also being retained in alignment for attachment to the reservoir, so that the motion of attaching a pipette tip to a pipette or instrument can also be used to immerse the distal end of the tip in the body in the liquid and draw the liquid into the pipette or instrument.
  • the analyte is loaded and disposed within the tip in lyophilized form, but may be initially loaded in non-lyophilized form and thereafter lyophilized in situ.
  • Figures 1-3 are elevation views, partially cut away, of pipette tips illustrating the incorporation of an analyte in a non-lyophilized liquid form, followed by lyophilizing in situ.
  • Figure 4 is a similar elevation view, partially cut away, of a pipette tip illustrating the containment of an analyte loaded in lyophilized or other solid form.
  • Figures 5-8 are similar elevation views, also partially cut away, illustrating various other embodiments of incorporation of preloaded analytes into pipette tips according to this invention.
  • Figure 9 is a pictorial view of a pipetting machine with a flexible tube connecting the machine to the pipette tip, with an enlarged view of a portion of the tube illustrating the incorporation of a preloaded analyte within the tube.
  • Figure 10 is a diagrammatic perspective view illustrating apparatus of the invention in which representative pipette tips containing analyte are retained in a package which also contains a quantity of carrier liquid, such that upon attachment of a preloaded pipette tip to a pipette or instrument, the required quantity of carrier liquid can also be drawn into the tip by a single operation.
  • FIGS 1-3 illustrate a pipette tip embodiment in which the desired analyte is initially loaded in a hydrated or liquid form, and subsequently lyophilized in situ within the tip
  • the analyte material 10 is, in this embodiment, either hydrated or in a fluidized form as indicated at 3
  • a barrier 5 Positioned across the interior of the barrel 8, near the distal end 24 of the tip 6 is a barrier 5 which will be permeable to the carrier liquid 26 but which offers sufficient flow resistance to the hydrated or fluidized form 3 of the analyte 10, so that upon loading the material 3 does not merely run out of the bottom of the tip
  • the tip 6 is then capped by a cap 7, which fits snugly within the top end 9 of the tip 6
  • the cap 7 has a slot or groove 11 formed in its bottom At the beginning of the lyophihzing process begins after loading the material 3 containing the analyte 10, the cap 7 is inserted into the top 9 and pushed down only far enough to leave a small segment of
  • FIGs 5-7 illustrate other convenient embodiments by which the analyte may be contained within the barrel 8 of the pipette tip 6
  • there are a plurality of small inert balls 16 If the balls are solid, they may have a coating of the analyte 10 on them Alternatively, if they are porous, analyte 10 may be coated across the outer surface and incorporated within the pores of the balls 16
  • the "balls" need not actually be spherical, they may be of any convenient physical form For instance, they may be of standard column packing shapes or other shapes which are convenient for receiving the coating of the analyte 10 and being loaded into the pipette tip 6
  • the balls 16 are retained in place by proximal barrier 14 and distal barrier 12
  • the analyte 10 need not be coated on each ball 16 Rather some of the balls 16 may be made of an inert nonsoluble material and other balls (designated 16') may be made in whole or in part from the analyte itself, such that
  • the embodiment shown has the analyte in the form of a solid annular plug 18 fitted tightly within the barrel 8 of the pipette tip 6 A hole 20 is left through the annular plug 18 to facilitate drawing in the carrier 26 to the pipette.
  • the distal barrier 12 is required, although a proximal barrier 14 may also be used if desired.
  • the analyte 10 is in the form of a porous solid body 22 (not particulated) and only distal barrier 12 is usually needed, although again both barriers may be present if desired.
  • Figure 8 illustrates another embodiment of the invention, similar to that previously illustrated in Figure 7.
  • Figure 8 illustrates that the analyte 10, whether granulated or as a massive solid, can be secured at any position along the length of barrel 8 of pipette tip 6. It is preferred, however, that the analyte 10 be positioned somewhere centrally of the barrel 8, as generally illustrated in Figures 1-4, rather than being near the distal end 24 or the upper end 4 of the pipette tip 6.
  • Proximal barrier 14 is normally hydrophilic, but in some cases (discussed below) it may initially be at least slightly hydrophobic. Similarly, distal barrier 12 will be either initially hydrophobic (designated as 12 in the Figures) or initially hydrophilic (designated as 12' in the Figures). Whether a barrier 12 or 14 is initially hydrophobic or hydrophilic will normally depend on the manner in which the analyte 10 is initially incorporated into the barrel 8 of the pipette tip 6 and the shelf life conditions of the preloaded pipette tips.
  • both barriers may be hydrophillic.
  • the barriers be at least slightly hydrophobic, to prevent absorption of moisture through the barriers and into contact with the preloaded solid analyte. This may be accomplished, if the barrier material itself is hydrophilic, by placing a thin hydrophobic coating over the outer surface (i.e., the surface which faces away from the analyte body 10) of each barrier. Conversely, the barriers may be made of material which is initially hydrophobic.
  • Figure 7 also illustrates an embodiment in which the solid analyte body 10 is to be formed in situ by deposition from or drying of an aqueous solution or slurry, other than as by lyophilization as illustrated in Figures 1-3.
  • Figure 7 illustrates a distal barrier 12' which is initially hydrophobic, so that the liquid can be poured into the barrel 8 and will be blocked from draining out by the hydrophobic barrier 12'.
  • Initial hydrophobicity may be imparted to the barrier 12' either by coating the inner surface (i.e., the surface which will face the analyte body 10) with a thin hydrophobic material, or the barrier 12' itself may be made of initially hydrophobic material.
  • proximal barrier 14 may optionally be emplaced. That proximal barrier may be either hydrophilic or hydrophobic, as discussed above. Since the carrier 26 will normally be water or an aqueous body fluid, it will be necessary to incorporate into the carrier an additive which will convert an initially hydrophobic barrier to a hydrophilic barrier. (The additive itself of course must not be detrimental to the analyte or affect the test results.) If the hydrophobicity was provided by a coating on a barrier, the hydrophobic coating must be rapidly dissolved by the additive. If the barrier itself was initially hydrophobic, the material from which it is made must be rapidly made hydrophilic by the additive.
  • hydrophilic means that the barriers (filters) will wet simultaneously with water, which has a surface tension of approximately 72 dynes/cm 2 at normal ambient room conditions.
  • Hydrophilic means that the barriers have sufficient surface tension of their own that they will not spontaneously wet with water, unless that surface tension is reduced.
  • a PTFE hydrophobic barrier would require reduction of surface tension to about 50 dynes/cm 2 to be wetted by pure water.
  • a wetting agent such as detergent or organic solvent with a surface tension of less than 32 dynes/cm 2 in the carrier to wet the barrier and make it hydrophilic.
  • Useful barrier materials include, but are not limited to, cellulose acetate, modified polyvinylidene fluoride, and nylon (all hydrophilic) and polytetrafluoro- ethylene (PTFE), polyvinylidene fluoride, and Immobilon XXX (all hydrophobic).
  • FIGS 1-8 illustrate the incorporation of the solid analyte into pipette tips.
  • Such preloaded tips represent an important end use of the present invention, and will be purchased by many laboratory, hospital, emergency care and other facilities for use in a wide variety of commonly conducted tests in which a pipetted reference standard is required. It will, however, also be recognized that the invention may be used in other test instruments and automated pipetting systems for reference samples where those instruments or systems operate in a manner akin to a typical pipette, by drawing in a predetermined quantity of carrier and forming a standard solution from the carrier and the specific quantity of preloaded analyte. Such a system is illustrated in Figure 9. An instrument 28 is shown generically.
  • This instrument may be any one of many different types which form a reference solution sample and a test solution sample and separate, compare specific predetermined properties of the two samples and then display a differential value reading for a desired property or for some other indication to a technician, such as on a display screen 30.
  • the reference sample is formed by drawing in carrier 26 through tubing 32
  • Tubing 32 terminates in a tip 34 which is inserted into a body of carrier 26 which is drawn upward through the tubing by a pump (not shown) within the instrument
  • a pump not shown
  • the carrier As the carrier is drawn up the tubing 32, it encounters a body of analyte 10 retained in place by barriers 12 and 14, in a manner similar to that shown in Figures 1-8
  • the carrier 26 passes through the barriers 12 and 14, simultaneously dissolving the analyte 10, such that when the resulting solution reaches the instrument through the remaining portion of tubing 32, it has formed a measured predetermined reference solution sample, as with the pipette systems
  • the analyte 10 be in the form of lyophilized or solid particles, granules, solid balls or coated balls rather than being in the form of a rigid solid body
  • the operator will normally place the pipette appendage 2 at the proximal end 4 of the preloaded pipette tip and couple the two together, normally simply by pushing the appendage 2 into the top 4 of the tip 6, as in the prior art procedures
  • the technician thus can use the same procedure that he or she is familiar with to secure the preloaded tip of this invention to the pipette
  • the pipette is then moved to a separate container of carrier 26 and the carrier is drawn in to the pipette by a conventional pipette mechanism, which is calibrated to draw in a precise predetermined quantity of carrier
  • the carrier 26 passes over and through the mass of the analyte 10 and rapidly dissolves, disperses or hydrates it completely To facilitate complete dissolution suspension or hydration, it will usually be desirable to have the carrier 26 completely fill not
  • the technician waits this length of time and then transfers the now formed mixture of analyte and carrier to a receptacle (such as test tube, petri dish, test instrument chamber or other similar conventional receptacle) into which is deposited the entire solution to form the control or reference sample.
  • a receptacle such as test tube, petri dish, test instrument chamber or other similar conventional receptacle
  • the emptied pipette tip will then commonly be discarded. Alternatively, however, it may in some cases be desirable for emptied tips to be collected for recycle by sterilization and refiling.
  • FIG 10 illustrates a further refinement of this system in which the preloaded pipette tip and the carrier can be obtained by the technician in a single operation and virtually a single motion.
  • a container 36 has a rack 38 mounted near its top.
  • a rack 38 mounted in the rack 38 are mounted a plurality of pipette tips 6. (In Figure 7, two pipette tips 6, one of which is shown partially cut away, are illustrated as representative.) It will be understood that initially all openings 40 of the rack 38 may, and normally will, also contain preloaded pipette tips.
  • the container 36 will be significantly deeper than the prior art pipette tip rack containers, such that the distal end 24 of a pipette tip 6 is positioned only part way down into the depth of the container 36. This leaves a volume (depth indicated at 42) which is used to contain a quantity of the carrier 26.
  • the carrier 26 may be loaded into the container 32 prior to closing and shipping, but more preferably the volume to house the carrier will be left empty during shipping. Thereafter, upon opening the package and readying it for use, the technician will pour a desired quantity of carrier 26 into the bottom portion of the container 36, normally to the depth 42, to fill the volume. Conveniently, one of the openings 40 in the grid 38 may be left vacant to facilitate the technician's transfer of the carrier 26 from a supply source to the interior of the container 36.
  • the rack or grid 38 will be made of a flexible material such that after the technician brings the pipette and its protrusion 2 into contact with and joins the upper portion 4 of the pipette tip 6, the technician can continue to push the assembled device downward, flexing the rack 38, until the distal end 24 of the pipette tip 6 is submerged in the body of carrier liquid 26.
  • the predetermined quantity of carrier 26 can then be readily drawn into the pipette via the pipette tip and through the body of analyte 10. Once the quantity of carrier liquid has been drawn into the pipette, the technician can merely lift the entire assembly directly out of the rack 38 and transport it to the target receptacle.
  • the rack 38 will also at that time resile to its previous position to keep the other remaining pipette tips out of the body of carrier 26 until each of them is to be submerged.
  • the grid 38 will be made of a material (such as a plastic material) which has some degree of flexibility but is still sufficiently rigid to support the pipette tip 6 while the pipette appendage 2 is being pushed into the upper portion 4, and also to resile immediately upon withdrawal of the pipette tip 6 to its previous position supporting the remaining pipette tips.
  • the tip is preloaded with a predetermined quantity of analyte, the pipette is chosen to draw in exactly the quantity of carrier desired, and the analyte dissolves rapidly and completely when contacted with the carrier. Consequently, the resulting solution is of an exactly known combination of carrier and analyte such that the properties of that solution are a precise and consistently repeatable standard.
  • the potential for technician error is essentially eliminated, since the technician does not measure either the amount of analyte or carrier used.
  • the dissolution is normally sufficiently rapid that it will be completed during the time it takes the technician to move the pipette from the carrier container to the target receptacle.
  • analyte materials which will be used with the preloaded pipette tips or tubing of the present invention include, but are not limited to, (1) materials obtained from human or animal body fluids such as blood, serum, plasma, urine, cerebrospinal fluid, pleural fluid, ascitic fluid, tears, sweat, saliva and amniotic fluid, (2) processed or purified human or animal proteins, peptides, lipids or carbohydrates in native, processed or synthetic human or animal body fluids, or (3) dried synthetic or semisynthetic human or animal body fluids, buffers or other stabilizing media containing various amounts of actual body fluids as in (1) above or purified or processed materials as in (2) above, or combinations thereof
  • the aqueous fluids such as blood, serum, plasma, urine, cerebrospinal fluid, pleural fluid, ascitic fluid, tears, sweat, saliva and amniotic fluid
  • processed or purified human or animal proteins, peptides, lipids or carbohydrates in native, processed or synthetic human or animal body fluids or (3) dried synthetic or
  • the devices and apparatus of the present invention may be used in a wide variety of end uses, including but not limited to analyses of bodily fluids such as blood, semen, urine, spinal fluid, saliva and sweat. It may also be used in any type of chemical or biological analysis where a test solution must be compared with a standard solution.
  • the system will thus find use in chemical and biological laboratories, medical facilities, including emergency rooms and similar locations. It is particularly useful in emergency medical situations and locations, such as being in the inventory of materials available on emergency response vehicles for people such as paramedics.
  • an emergency medical technician can simply use the current invention to withdraw a sample of bodily fluid (such as blood) from the patient into the pipette (usually by having a hypodermic needle tip at the end of the pipette tip) and then dispense the resulting solution into a test device within the emergency vehicle, such that test results can be available for the emergency room physician by the time the patient is delivered to the hospital.
  • a sample of bodily fluid such as blood
  • the technician can quickly obtain valuable data about the patient's condition for the subsequent attending physician.
  • the system is ideal for other applications where rapid results are needed, such as in running tests in an emergency room to make a rapid diagnosis of a received patient's condition, or where a large number of identical samples need to be run in a fixed period of time. Because this system can be repeated quickly and accurately, a laboratory technician can increase his or her productivity significantly by being able to make numerous consistent repeat samples in the time previously required for production of only a single sample. Further, because none of the samples formed by this invention have time before use for the carrier/analyte solution to deteriorate significantly, all of the samples will be of equivalent accuracy and no time consuming and potentially inaccurate time calibrations or corrections need to be made
  • the analyte 10 need not be a single material, but in fact can be a plurality of different materials, all of which are rapidly soluble in the same carrier 26, but which can be used for reading of different properties or conditions of a patient
  • the individual analytes 10 must not interact with each other in a manner which would adversely affect the test readings
  • different materials within the analyte 10 which are themselves interactive but which do not react until they are both immersed in the carrier 26 This also allows for great stability and long shelf life, since the analyte will have the shelf life of lyophilized materials, and solution or dispersion resulting from the combination of the preloaded analyte and the drawn carrier will not deteriorate significantly in the short time from its formation to its use
  • the preloaded pipette tips, instrument tubing, and the like products will find use in many test and analysis procedures These include, but are not limited to, blood chemistries tests such as for sodium, potassium, glucose and urea creatinine XXX, enzyme chemistries such as creatine kinase, lactate dehydrogenase, serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphate, cardiac emergency room chemistries such as creatine kinase MS, troponin T&l and myoglobin, serum protein electrophoresis and other electrophoretic tests to serve as position markers for the various protein or other analyte bands for proper identification, standards and control materials for all types of immunological tests, including for arthritis, lupus erythematosis, scleroderma, hepatitis and HIV, diabetes testing for glycated hemoglobin and other abnormal hemoglobins such as fetal and hemoglobin S,

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  • General Health & Medical Sciences (AREA)
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  • Quality & Reliability (AREA)
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  • Sampling And Sample Adjustment (AREA)

Abstract

La présente invention concerne un appareil et des dispositifs permettant d'obtenir de façon rapide, régulière, rigoureuse et précise des solutions étalons utilisées comme échantillons témoins, en éliminant le risque d'erreurs, les coûts excessifs, et les problèmes de déchets ou de dégradation. L'échantillon témoin est obtenu en amenant le support (26) par le tube (32). Le tube (32) se termine par un embout (34) qui est introduit dans un corps de support (26) amené vers le haut à travers le tube (32) par une pompe placée dans l'instrument. Lorsque le support est amené vers le haut du tube (32), il rencontre un corps d'analyte (10) retenu sur place par des barrières (12 et 14). Le support (26) passe à travers les barrières (12 et 14) faisant dissoudre simultanément l'analyte (10), de sorte que lorsque la solution résultante arrive à l'instrument par la partie restante du tube (32), on obtient un échantillon mesuré et prédéterminé de solution témoin, comme avec le système de pipettes. Puisque le tube (32) est flexible, il est préférable d'utiliser un analyte (10) sous forme de particules solides ou lyophilisées, de granules, de billes solides ou enrobées, qu'un analyte sous forme d'un corps solide et rigide.
PCT/US1998/016137 1997-08-01 1998-07-31 Instruments de pipetage preremplis avec des echantillons temoins etalonnes WO1999006149A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU20349/99A AU2034999A (en) 1997-08-01 1998-07-31 Pipetting devices preloaded with standardized control sample materials

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WO2005077537A1 (fr) 2004-02-11 2005-08-25 Pamgene B.V. Dispositif permettant d'analyser une interaction entre des molecules cibles et des molecules sondes
DE102004046366A1 (de) * 2004-07-15 2006-02-09 Levin, Felix, Dr. Universell einsetzbare Testvorrichtung zur schnellen Analysen von Flüssigkeiten
EP1688181A2 (fr) * 2005-02-05 2006-08-09 Eppendorf Ag Embout de pipette avec filtre
EP1828746A2 (fr) * 2004-10-18 2007-09-05 Applera Corporation Dispositif de traitement de fluide comprenant un modulateur d'ecoulement de materiau composite
EP2103680A1 (fr) * 2007-01-19 2009-09-23 Universal Bio Research Co., Ltd. Pipette ayant un support/fluide enfermé à l'intérieur, appareil destiné au traitement d'une pipette ayant un support/fluide enfermé à l'intérieur et procédé de traitement d'une pipette ayant un support/fluide enfermé à l'intérieur
EP2147723A1 (fr) * 2008-07-16 2010-01-27 Ortho-Clinical Diagnostics, Inc. Utilisation d'un embout pour aspiration/distribution de liquides comme tube de microcentrifugation
WO2013137756A1 (fr) * 2012-03-12 2013-09-19 INSTITUTO POLITéCNICO DE LEIRIA Embout de pipette pour centrifugeuse comprenant deux fermetures
CN103990503A (zh) * 2014-05-16 2014-08-20 临沂大学 一次性移液枪涂布枪头及其使用方法
EP2932234A4 (fr) * 2012-12-12 2016-11-23 Bio Rad Laboratories Procédé et système d'étalonnage

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Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005077537A1 (fr) 2004-02-11 2005-08-25 Pamgene B.V. Dispositif permettant d'analyser une interaction entre des molecules cibles et des molecules sondes
DE102004046366A1 (de) * 2004-07-15 2006-02-09 Levin, Felix, Dr. Universell einsetzbare Testvorrichtung zur schnellen Analysen von Flüssigkeiten
US8062611B2 (en) 2004-10-18 2011-11-22 Applied Biosystems, Llc Fluid processing device including composite material flow modulator
US8383062B2 (en) 2004-10-18 2013-02-26 Applied Biosystems, Llc Fluid processing device including size-changing barrier
US8147770B2 (en) 2004-10-18 2012-04-03 Applied Biosystems, Llc Microfluidic device including a dissolvable structure for flow control
EP1828746A2 (fr) * 2004-10-18 2007-09-05 Applera Corporation Dispositif de traitement de fluide comprenant un modulateur d'ecoulement de materiau composite
EP1828746A4 (fr) * 2004-10-18 2009-09-02 Applera Corp Dispositif de traitement de fluide comprenant un modulateur d'ecoulement de materiau composite
DE102005005437A1 (de) * 2005-02-05 2006-08-10 Eppendorf Ag Filterpipettenspitze
US9138741B2 (en) 2005-02-05 2015-09-22 Eppendorf Ag Filter pipette tip
EP2283926A1 (fr) * 2005-02-05 2011-02-16 Eppendorf Ag Embout de pipette avec filtre
EP1688181A2 (fr) * 2005-02-05 2006-08-09 Eppendorf Ag Embout de pipette avec filtre
EP1688181A3 (fr) * 2005-02-05 2006-08-30 Eppendorf Ag Embout de pipette avec filtre
US8192699B2 (en) 2005-02-05 2012-06-05 Eppendorf Ag Filter pipette tip
EP2103680A1 (fr) * 2007-01-19 2009-09-23 Universal Bio Research Co., Ltd. Pipette ayant un support/fluide enfermé à l'intérieur, appareil destiné au traitement d'une pipette ayant un support/fluide enfermé à l'intérieur et procédé de traitement d'une pipette ayant un support/fluide enfermé à l'intérieur
EP2103680A4 (fr) * 2007-01-19 2013-01-02 Universal Bio Research Co Ltd Pipette ayant un support/fluide enfermé à l'intérieur, appareil destiné au traitement d'une pipette ayant un support/fluide enfermé à l'intérieur et procédé de traitement d'une pipette ayant un support/fluide enfermé à l'intérieur
US8323585B2 (en) 2008-07-16 2012-12-04 Ortho-Clinical Diagnostics, Inc. Use of fluid aspiration/dispensing tip as a microcentrifuge tube
EP2147723A1 (fr) * 2008-07-16 2010-01-27 Ortho-Clinical Diagnostics, Inc. Utilisation d'un embout pour aspiration/distribution de liquides comme tube de microcentrifugation
WO2013137756A1 (fr) * 2012-03-12 2013-09-19 INSTITUTO POLITéCNICO DE LEIRIA Embout de pipette pour centrifugeuse comprenant deux fermetures
EP2932234A4 (fr) * 2012-12-12 2016-11-23 Bio Rad Laboratories Procédé et système d'étalonnage
US9810703B2 (en) 2012-12-12 2017-11-07 Bio-Rad Laboratories, Inc. Calibration process and system
CN103990503A (zh) * 2014-05-16 2014-08-20 临沂大学 一次性移液枪涂布枪头及其使用方法
CN103990503B (zh) * 2014-05-16 2015-09-09 临沂大学 一次性移液枪涂布枪头及其使用方法

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