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US3650698A - Apparatus for the automatic determination of the coagulation, aggregation and or flocculation, or the like, rates of fluids, and novel reaction intensifying agent for use therewith - Google Patents

Apparatus for the automatic determination of the coagulation, aggregation and or flocculation, or the like, rates of fluids, and novel reaction intensifying agent for use therewith Download PDF

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US3650698A
US3650698A US881971A US3650698DA US3650698A US 3650698 A US3650698 A US 3650698A US 881971 A US881971 A US 881971A US 3650698D A US3650698D A US 3650698DA US 3650698 A US3650698 A US 3650698A
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Prior art keywords
reaction
reagent
intensifying agent
blood plasma
fluid
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US881971A
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Stanford L Adler
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Technicon Corp
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Technicon Corp
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/4905—Determining clotting time of blood
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/451—Magnetic mixers; Mixers with magnetically driven stirrers wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
    • 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
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/808—Automated or kit
    • 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
    • Y10T436/110833—Utilizing a moving indicator strip or tape
    • 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
    • Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream

Definitions

  • ABSTRACT Apparatus for the determination of the coagulation rate or the like of fluids, wherein dispensing means are operable to suecessively dispense blood plasma samples, in turn and at a precisely metered rate, onto spaced-apart measured quantities or spots of a dried suspension of a reaction intensifying agent carried on an advancing film strip.
  • the intensifying agent may comprise magnetic iron oxide particles.
  • additional dispensing means are operable to dispense a precisely mete red quantity of prothrombin reagent into the film strip.
  • the resulting sample-reagent-intensifying agent mixture is subjected to rotating magnetic fields, with the result that the moving magnetic particles promote mixing and, also, are operative to collect one or more of the fibrin strands, whereby the mixture, which is substantially turbid, undergoes a sharp change in its optical transmission properties, which change is detected by 1i ght sensitive means for the measurement of the prothrombin time of the blood plasma sample of interest.
  • Another object of this invention is the provision of apparatus as above which operate to substantially minimize the amount of the expensive thromboplastin reagent required for a blood plasma sample Prothrombin Time determination to thus materially reduce the cost of such determination.
  • Another object of this invention is the provision of a novel coagulation reaction intensifying or enhancing agent which provides for sharp and dramatic change in a readily discernible and/or automatically detectable characteristic of the blood plasma sample-thromboplastin reagent mixture at the end point of the coagulation reaction,
  • Another object of this invention is the provision of apparatus as above which are particularly adapted for operation with undiluted blood plasma samples.
  • a further object of this invention is the provision of apparatus as above which are fully and continuously automatic in operation and provide a readily interpretable, permanent readout of the determined blood plasma sample Prothrombin Times to thus eliminate most major sources of technicianoccasioned inaccuracy.
  • a still further object of this invention is the provision of apparatus as above which require the use of only readily available components of proven dependability in the fabrication thereof to thus insure long periods of satisfactory, substantially maintenance-free apparatus operation.
  • the apparatus of my invention comprise sample supply means which supply a stream consisting of successive ones of said blood plasma samples, and blood plasma sample dispensing means which are operable to successively dispense said blood plasma samples at a precisely metered rate.
  • a novel coagulation reaction intensifying or enhancing agent which comprises opaque magnetic iron oxide particles as the essential ingredient thereof is supplied in the form of spaced, measured quantities or spots of a dried suspension of said agent as disposed on suitable carrier means which take the form of a substantially transparent film strip.
  • Automatically operable thromboplastin reagent dispensing means are provided and function to dispense precisely metered minimum quantities of said thromboplastin reagent upon demand. Further included are temperature controlled means to effect blood plasma sample incubation and bring the same to appropriate coagulation reaction temperature, rotating magnetic field generation means to generate a rotating magnetic field through said temperature controlled means, and light sensitive detection means to automatically detect the end point of the coagulation reaction and provide the desired Prothrombin Time determination accordingly.
  • said film strip is advanced to a first position on said temperature controlled means whereat a precisely measured quantity of a blood plasma sample is added to said reaction intensifying or enhancing agent to rapidly re-suspend the latter with the effect of said rotating magnetic field being to promote initial blood plasma sample-intensifying or enhancing agent mixing and render the resultant mixture substantially turbid or opaque.
  • the film strip is advanced to said reagent dispensing means whereat a precisely metered quantity of the thromboplastin reagent is added to the substantially turbid or opaque blood plasma sample-intensifying or enhancing agent mixture to commence the coagulation reaction with the effect of said magnetic field on said magnetic iron oxide agent further promoting thorough blood plasma sample-thromboplastin reagent mixing.
  • the film strip is advanced to the operation position of said light sensitive detecting means, which position generally coincides with the center of said rotating magnetic field.
  • the substantially turbid or opaque blood plasma sample-thromboplastin reagent-intensifying agent mixture will undergo a sharp and dramatic change in optical property through the collection of the rotating magnetic iron oxide particles in one or more of the fibrin strands generally centrally of the mixture to thus render the latter substantially transparent for immediate detection by said light sensitive detecting means, and attendant provision of a printed readout of the Prothrombin Time of the blood plasma sample of interest. Operation of the apparatus is continuous in the manner described until each of the blood plasma samples of said successive stream thereof has been determined.
  • FIG. 1 is a flow diagram depicting the new and improved apparatus of my invention
  • FIG. 2 is a top plan view ofa portion of the film strip carrier of the apparatus of FIG. 1 illustrating the disposition of the measured quantities or spots of the reaction intensifying agent thereon;
  • FIG. 3 is a top plan view ofa portion of the film strip carrier of FIG. 2 illustrating the manner in which the reaction intensifying agent promotes blood plasma sample-thromboplastin mixing;
  • FIGS. 4 and 5 illustrate the sharp and dramatic change in the turbidity of the blood plasma sample-reagent-reaction intensifying agent mixture attendant the completion of the coagulation reaction.
  • sample supply means which may, for example, take the general form of those shown and described in U.S. Pat. 3,134,263 issued May 26, I964 to Edward B. M. DeJong, are indicated generally at and comprise a turntable 12 upon which is disposed a circular array of blood plasma sample containers 14.
  • a sample off-take device is indicated at 16 and comprises a sample off-take probe 18 and probe operating means 20, respectively.
  • a wash liquid receptacle 22 is disposed as shown adjacent the turntable 12, while sample supply device drive means are indicated at 24 and are operative to drive each of the turntable l2 and the sample off-take probe operating means in the manner described directly hereinbelow as indicated by the dashed lines extending therebetween.
  • the turntable I2 is intermittently rotated, or indexed, to present each of the blood plasma sample containers 14 in turn to the sample off-take probe 18, while the latter is in turn intermittently operated to immerse the inlet end ofthe off-take probe 18 in a thusly presented sample container for a predetermined period of time to aspirate (as described in detail hereinbelow) a predetermined measured volume ofthe blood plasma sample therefrom, to then transfer the said off-take probe inlet end through the ambient air for immersion in the wash liquid receptacle 22 for a predetermined period of time to thus aspirate a predetermined measured volume of ambient air followed by a predetermined measured volume of said wash liquid therethrough, and to then again transfer the said off-take probe inlet end through the ambient air for immersion in the next presented sample container 14 for a predetermined period of time to thus aspirate another predetermined measured volume of ambient air therethrough and commence the aspiration ofa predetermined measured volume of the blood plasma sample from said next presented sample container.
  • a fluid stream consisting of successive, predetermined measured volumes of said blood plasma samples as spaced, in each instance, by a segment of air, a segment of the wash liquid from wash liquid receptacle 22, and a segment of air, respectively, will be supplied to the sample off-take probe 18.
  • a compressible tube or peristaltic proportioning pump which, for example, may take the general form of that shown and described in U.S. Pat. 3,227,091 issued Jan. 4, 1966 to Jack Isreeli, et al., is indicated generally in dashed lines at 26 and, as utilized herein, may be understood to comprise a plurality of resilient, compressible pump tubes 28, 30, 32 and 34, respectively, each of which is progressively compressible or occludable by a plurality of non-illustrated pump rollers, in synchronous manner, to pump fluids therethrough in the direction from right to left as indicated by the flow directional arrows in FIG. 1.
  • compressible pump tube 30 is connected as shown to the outlet end of the blood plasma sample off-take probe 18 to provide for the aspiration of the blood plasma sample-wash liquid-air stream therethrough as discussed hereinabove.
  • the outlet end of compressible pump tube 30 is connected as shown to one inlet ofajunction conduit 36, and the outlet of the latter is connected to a blood plasma sample supply conduit 38.
  • the inlet end of compressible pump tube 28 is left open as shown to atmosphere, while the outlet end thereof is connected to one inlet of three-way valve means 40.
  • One outlet conduit 42 of the three-way valve means 40 extends as indicated to atmosphere, while the other outlet conduit 44 of said three-way valve means is connected to the other inlet of the junction conduit 36.
  • a reagent container is indicated at 46 and, for use as disclosed herein in determining the end point of the blood coagu lation reaction, or Prothrombin Time, of the blood plasma samples from sample supply means 10, may be understood to contain a suitable supply of thromboplastin reagent as indicated at 48.
  • a reagent supply conduit 50 is disposed as shown within the reagent supply container 46 so that the inlet end of the former is in close proximity to the bottom of the latter for obvious purpose, and the outlet end of reagent supply conduit 50 is connected as shown to the inlet end of compressible pump tube 32, whereby is believed made clear that operation of the peristaltic pump 26 will result in the pumping of the reagent 48 from said supply container through said compressible pump tube in the indicated direction.
  • the outlet end of compressible pump tube 32 is connected as shown to one inlet ofajunction conduit 52, while the outlet of said junction conduit is connected to a reagent dispensing conduit 54.
  • a reagent by-pass and return conduit is indicated at 56, and the inlet end thereof is connected as shown to the other outlet of the junction conduit 52, while the outlet end of said reagent by-pass and return conduit extends as shown into the reagent supply container 46 for the return of the thromboplastin reagent thereto as described in detail hereinbelow.
  • Temperature control means which include a heating coil 58 connected as shown in the reagent supply conduit 54 adjacent the outlet end of the latter, and a temperature control bath as indicated in dashed lines at 60, are included to enable the precise control of the temperature of the thromboplastin reagent immediately prior to the dispensing thereof from said conduit outlet end as described in detail hereinbelow.
  • a suction conduit for reagent return is indicated at 62 and is connected as shown to the reagent supply conduit 54 immediately adjacent the outlet end of the latter.
  • the outlet end of the suction conduit 62 is connected as shown to the inlet end of compressible pump tube 34, while the outlet end of the latter is connected to the inlet end of a reagent return conduit 64 which extends as shown to within the reagent supply container 46 to providefor the return of the thromboplastin reagent thereto, against as described in detail hereinbelow.
  • a supply roll of a strip of a film substrate 66 which is made from any material having suitable strength, light transmission, and chemical inertness characteristics in the nature, for examshown on rotatable support means as indicated at 68..
  • measured quantities or spots 70 of a dried suspension of a reaction intensifying or enhancing agent are disposed at substantially equally spaced intervals on the upper surface of the film strip 66.
  • said reaction intensifying agent may be understood to comprise substantially opaque particles of a paramagnetic material such as magnetic iron oxide particles of the nature used in the manufacture tape, as homogeneously suspended before drying in a suitable carrier solution.
  • Magnetic iron oxide particles of this nature are of generally acicular configuration and have a major dimension in the range of 0.40 to 0.60 microns. Alternatively, such particles may be constituted by cobalt or nickel oxide particles.
  • said reaction intensifying agent may consist of a suspension of approximately 50 grams percent magnetic iron oxide particles in approximately 25 percent PVP which contains approximately 5 percent glycerine, before drying, and said suspension may be applied to the film strip 66 for the formation of the spots 70 in any appropriate manner as, for example, through the use of well-known silk screening techniques.
  • the pH of the reagent intensifying or enhancing agent is adjusted, if necessary, to insure that the same will not react with the thromboplastin reagent upon the mixture thereof.
  • the particular PVP and glycerine constituents of the magnetic iron oxide particle suspension may be understood to be particularly effective in in suring the desired, substantially instantaneous re-suspension of said iron oxide'particles in an aqueous solution upon the mixture thereof with the respective blood plasma samples as described in detail hereinbelow. It is, however, believed clear that other and different suspensions of said magnetic iron oxide particles in other and different relative percentaged with regard to said PVP and glycerine constituents, and/or with other and different suspending agents, may prove equally useful.
  • Boundary means in the nature of those indicated at 72 in F1 2 will preferably be formed on the film strip 66 in any appropriate manner as, for example, through embossing of the latter, to effect the substantial containment in the indicated area of the reaction intensifying or enhancing agent and the respective blood plasma samples upon the re-suspension of the former in the latter as described in detail hereinbelow.
  • Heat sink means having a substantially level, flat upper surface are indicated at 74, and heating coil means 76 are disposed as shown adjacent the lower surface of said heat sink means to provide for the substantial maintenance of the latter at a desired temperature as should be obvious.
  • a mirror 78 is disposed as shown in the heat sink means 74 in such manner that the upper surface of said mirror is substantially flush with the upper surface of said heat sink means.
  • Film strip guide and drive means are provided and comprise an idler roller 80, a film strip advance drive roller 82, and a film strip pressure roller 84 cooperatively associated with the latter as shown. Accordingly, intermittent driven rotation of from the film strip supply roll, the passage thereof beneath idler roller 80, the passage thereof over the upper surface of heat sink means 74 in close contact therewith, and the sub- 88 and may be seen to comprise a suitable, generally cylindrical opaque housing 90 having a focusing lens 92 disposed therein as shown.
  • a light source is indicated at 941, and light detection means which may, for example, take the form of a photoelectric cell, are indicated at 96, and each of said light source and said photoelectric cell are positioned within the housing 90 as shown in such manner that the light beam will be focused as indicated by the focusing lens 92 for impingement upon the mirror 78 and reflection therefrom for refocusing by the focusing lens 92 for impingement upon the active surface of the photoelectric cell 96.
  • Reaction timer and readout printing means are indicated schematically at 98 and are operatively associated as shown with the photoelectric cell 96 to provide for reaction timing and readout printing on a tape 99 as described in detail hereinbelow.
  • a bar magnet of appropriate field strength is indicated at 100 and is supported as shown for rotation at appropriate rate through operation of drive motor means 102 to thereby establish a rotating magnetic field, the lines of force of which will, of course, extend through and above the heat sink means 74.
  • the bar magnetic 100 is disposed relative to the mirror 78 in such manner that the respective centers thereof are in substantial vertical alignment as seen in FIG. 1, whereby it may be understood that the center of the rotating magnetic field established by rotation of the bar magnet 100 will be generally coincident with the center of the mirror 78.
  • Multi-element snap-action valve means are indicated generally in dashed lines at 104 and may, for example, take the general form of those shown and described in the co-pend ing application for United States Patent of Carl V, Johnson et al., entitled New and Improved Method and Apparatus for Simultaneously Controlling the Flow of Fluids in a Plurality of Flow Paths, Ser. No. 864,262, filed Sept. 22, 1969 and assigned to the assignee hereof.
  • each of the reagent by-pass and return conduit 56, the reagent dispensing conduit 54, and the suction conduit 62 pass as shown through the valve means 104 for control by the latter of the respective fluid flows therethrough and, to this effect, it may be understood that at least the portion of each of said conduits which passes through said valve means is constituted by a compressible tube or conduit as indicated respectively at 106, 108 and 110.
  • the valve means 104 comprise a valve actuator member 111 having projection bar members 112, 114, and 116 formed thereon with said bar members being respectively operatively associated with the compressible conduit portion 106, and 110.
  • the valve means 104 are arranged so that the valve actuator 111 is pivotally moveable, in extremely rapid, snap-action manner between a first position thereof wherein bar member 114 contacts and substantially compresses or occludes compressible conduit portion 108 against a non-illustrated platen to substantially prevent fluid flow therethrough, while neither of bar members 112 or 116 contacts compressible conduit portions 106 and and thus does not interfere with the respective flow of fluids therethrough, to a second position of said valve actuator wherein bar members 112 and 116 respectively contact and substantially compress or occlude compressible conduit portions 106 and 110 against said platen to substantially prevent fluid flow therethrough, while bar member 114 does not contact compressible tube portion 108 and thus does not interfere with the flow of fluids therethrough.
  • valve actuator 111 in said first position thereof, fluid flow through reagent dispensing conduit 54 will be substantially prevented. while fluid flow through the respective reagent by-pass and return conduits 56 and suction conduit 64 will be unaffected. Conversely, with said valve actuator 111 in said second position thereof, it is believed clear that fluid flow through the respective reagent by-pass and return conduit 56 and suction conduit 64 will be substantially prevented, while fluid flow through reagent dispensing conduit 54 will be unaffected.
  • a blood plasma sample dispensing probe is indicated at 120 and the inlet end thereof is connect-ed as shown to the outlet end of blood sample supply conduit 38.
  • the blood sample dispensing probe 120 is supported as shown adjacent the outlet end thereof from the arm 122 of blood sample dispensing probe operating means 124.
  • the blood sample probe operating means 124 are operated from drive motor means as indicated at 126A for oscillatory movement to move the inlet end of the blood sample dispensing probe 120 in an arc between the depicted first position thereof wherein said outlet end is in substantial vertical alignment with a measured quantity or spot 70 of the reagent intensifying or enhancing agent on the upper surface of film strip 66 when the latter is in a specific position thereof as described in detail hereinbelow, and a second position of the probe as depicted in phantom in FIG. 1 wherein said dispensing probe outlet end is in general vertical alignment with a blood plasma sample and wash liquid collection receptacle 126A which leads as indicated to waste.
  • Programmer means which may take any appropriate form in the nature, for example, of cam-operated electrical programmer means are indicated schematically at 128 and are operatively connected as indicated by the dashed lines to each of the sample supply means drive motor 24, the three-way valve means 40, the multi-element valve means 104, the blood plasma sample dispensing probe operating means drive motor 126, the film strip advance drive roller drive motor 86, the photoelectric cell 96, and the timer and readout printing means 98, respectively.
  • each of the blood plasma sample containers 14 would contain an undiluted blood plasma sample from a different patient, each of which will have been previously treated in classical manner with a fixative reagent in the nature of sodium oxalate or sodium citrate immediately upon withdrawal from the patient, and will preferably be maintained at approximately 4 to 5 C. in the relevant blood plasma sample container 14 to inhibit clotting factor deterioration through the use of non-illustrated cooling means which may be included in or operatively associated with the sample supply device 10.
  • the three-way valve means 40 would be arranged to operate, under the control of programmer 128, to be in the second position thereof to introduce air to the blood plasma sample-wash liquid-air stream flowing through junction conduit 36 only when the wash liquid segments are flowing therethrough to thus air segment each of said wash liquid segments to materially improve the cleansing action thereof, while insuring the flow of each of the aspirated blood plasma samples as a continuous stream to the blood plasma sample dispensing probe 120.
  • the reagent supply container 46 would, of course, contain a supply of the thromoplastin reagent 48 sufficient for the Prothrombin Time determination of each of the blood plasma samples carried from the sample supply means 10.
  • the film strip advance drive roller motor 86 would be arranged to operate the film strip advance drive roller 82, under the control of programmer 128, to alternatively, intermittently advance the film strip 66 to two positions thereof relative to the focal point of lens 92, the outlet end of reagent dispensing conduit 54, and the outlet end ofthe blood plasma sample dispensing probe 120, respectively, and to ena ble the dwelling of said film strip in each of said positions for different predetermined periods of time as described in detail hereinbelow. More specifically, it may be understood that said film strip advance drive roller would initially be operated to advance the film strip to the position thereof depicted in FIG.
  • a leading measured quantity or spot 70 of the reaction intensifying or enhancing agent (as now thoroughly mixed and re-suspended with a blood plasma sample and a precisely metered amount of the thromboplastin reagent in the manner described in detail hereinbelow) would be disposed as indicated at position C on the mirror 78 at the exact focal point of the focusing lens 92, while the next succeeding or trailing measured quantity or spot 70 of said reaction intensifying or enhancing agent would be disposed as indicated at position A directly below the outlet end of blood plasma sample dispensing probe when the same is in the depicted blood plasma sample dispensing position thereof as shown in FIG. 1.
  • the spacing 5 (FIG 2) between said measured quantities or spots 70 of the reaction intensifying or enhancing agent on the upper surface of the film strip 66 is predetermined to substantially coincide with the distance between said lens focal point on mirror 78 and the point on heat sink 74 which is in substantial vertical alignment with the outlet end of the blood plasma sample dispensing probe 120.
  • the former would be positioned so that the measured quantity or spot 70 of the reaction intensifying or enhancing agent which had been disposed at position A would now be advanced for disposition in substantial vertical alignment with the outlet end of reagent dispensing conduit 54 at position B as indicated in FIG. 1, it being believed clear that with the film strip 66 thusly disposed, no measured quantities or spots 70 of the reaction intensifying or enhancing agent will be disposed at either of positions A or C.
  • the multi-element valve means 104 would be arranged to operate, again under the control of programmer 128, to be in said second position thereof to enable reagent flow from reagent supply conduit 32 through compressible conduit portion 108 to reagent dispensing conduit 54 only for a period of time predetermined to substantially coincide with the period of time in which the film strip 66 is dwelled in a said second position thereof to position a measured quantity or spot 70 of the reaction intensifying or enhancing agent in substantial vertical alignment with the outlet end of said reagent dispensing conduit.
  • the multielement valve means 104 would be arranged to be in said first position thereof to permit fiuid flow only through compressible conduit portions 106 and 110.
  • temperature control bath 60 would be arranged to maintain the temperature of the temperature control coil 58 at approximately 37 C. to thus insure the dispensing of the thromboplastin reagent at substantially this temperature.
  • the blood plasma sample dispensing probe operating means 124 would be arranged to operate, through drive motor 126A under the control of programmer 128, to position the blood plasma sample dispensing probe 120 as depicted in the blood plasma sample dispensing position thereof only for a part of the time when the film strip 66 is dwelled in a said first position thereof with a measured quantity or spot 70 of the reagent intensifying or enhancing agent being disposed as depicted in FIG. 1 at position A, and to at all other times position said blood plasma sample dispensing probe in the position depicted in phantom in FIG. 1 whereby the remainder of each of the blood plasma samples that is not dispensed for test, and the respective inter-sample wash liquid segments, will be dispensed into receptacle 126 for flow therefrom to waste.
  • heating coil means 76 would be arranged to operate to maintain the temperature of the heat sink means 74 at approximately 37 C.
  • the blood plasma sample dispensing probe operating means will be actuated to move said probe to said second position thereof directly over wash-liquid collection receptacle 126 to enable the flow of the remainder of the blood plasma sample, and the succeeding air segment, air segmented wash liquid segments, and air segments, through said blood plasma sample dispensing probe to insure a thorough cleansing of the latter and prevent the contamination of the succeeding blood plasma sample by the residue of the just dispensed blood plasma sample, to obvious advantage.
  • the film strip advance drive roller 82 will, at this point, be maintained stationary for approximately 55 seconds to dwell the film strip 66 in this first position thereof for that period of time to bring the thusly dispensed blood plasma sample and the measured quantity or spot 70 of the reaction intensifying or enhancing agent up to the preferred test tempera ture of approximately 37C. and commence the required incubation of said blood plasma sample.
  • the film strip advanced drive roller 82 will be operated to advance the film strip 66 to said second position thereof wherein the now thoroughly mixed blood plasma sample and reagent intensifying or enhancing agent measured quantity 70 will be disposed at position B directly beneath the outlet end of reagent dispensing conduit 54.
  • the multielement valve means 104 will be rapidly shifted to the second position thereof to enable the commencement of reagent dispensing, in precisely metered amount, through the reagent dispensing conduit 54 at approximately 37C.
  • the time of shifting of the multi-element valve means to said second position thereof may be taken as time 0 and communicated from the programmer 128 to the timer and readout printing the means 98 since this time substantially coincides with the time the thromboplastin reagent first contacts said blood plasma sample to commence the coagulation reaction.
  • multi-element valve means 104 will be rapidly shifted to return to said first position thereof wherein further reagent flow from reagent supply conduit 32 to reagent dispensing conduit 54 will be prevented by the abrupt closure of compressible conduit portion 108, and the supply of reagent being pumped through compressible pump tube 32 by-passed instead through reagent by-pass and return conduit 56 for return to reagent supply container 46.
  • This shifting of the multi-element valve means to said second position thereof will, in addition, be effective to open compressible conduit portion with attendant creation of considerable suction in suction line 62 through the operation of compressible pump tube 34 to thus insure that any thromboplastin reagent remaining in the outlet end portion of the reagent dispensing conduit 54 after the completion of reagent dispensing is sucked therefrom through the suction 62 for return to reagent supply container 46 on reagent return conduit 64 to thus further insure the precise dispensing of exactly the desired amount, only, of said reagent and substantially prevent any waste of the latter to obviously significant ad vantage.
  • the film strip advance drive roller 82 is operated to again advance the film strip 66 to a said first position thereof wherein the blood plasma sample-reagent-reagent intensifying or enhancing agent mixture under discussion will be advanced to position C which, as discussed hereinabove, substantially coincides with the focal point of focusing lens 92 on mirror 78.
  • this blood plasma sample-reagent-reaction intensifying agent mixture is at this point still substantially opaque or turbid due to the wide distribution of the substantially opaque magnetic iron oxide particles therein, the movement of the said mixture into position C will function to break the beam of light from light source 94 to said photoelectric cell, and that this occurrence may be utilized for the provision ofa control signal to programmer 128 to immediately discontinue operation of the film strip advance drive roller drive motor 86 as should be obvious.
  • FIG. 4 depicts the blood plasma sample-reagent-reaction intensifying agent mixture as the same initially assumes position C and clearly illustrates that the said mixture is, at this point, substantially turbid or opaque due to the substantially even distribution of the multitude of magnetic iron oxide particles therein.
  • the interaction between the fibrin strands and said magnetic iron oxide particles, and collection thereof in one or more relatively large globules as indicated at 73 in FIG. 5 will result in a rapid and dramatic change in the optical characteristics of the said mixture to those depicted in FIG. 5, wherein the said fibrin-magnetic iron oxide particle globules will be collected generally centrally of said mixture to result in sharp and dramatic change in the light transmission properties thereof from the substantially turbid or opaque to the substantially translucent or transparent.
  • Operation ofthe apparatus of my invention is, of course, automatically continuous as described until the Prothrombin Time for each of the blood plasma samples supplied from sample supply device has been determined.
  • 60 of said blood plasma samples may be positioned at one time on the sample supply means turntable l2, and approximately only one hour will be required for the determination of the Prothrombin Times of all of said blood plasma samples.
  • the apparatus of my invention may be understood to make possible the precise and automatic determination of the Prothrombin Time of an undiluted blood plasma sample in a ratio of approximately 0.02 ml. of thromboplastin reagent to each 0.01 ml. of blood plasma sample as opposed, for example, to blood plasma sample Prothrombin Time determination made in accordance with the principles of the prior art which require approximately 0.2 ml. of thromboplastin reagent per 0.1 ml. of blood plasma sample.
  • the apparatus of my invention make possible a very substantial and significant reduction of approximately percent in the amount of expensive thromboplastin reagent required per blood plasma sample Prothrombin Time determination.
  • the apparatus of my invention would have significant utilization for different purposes. More specifically, it is believed clear that through suitable modification the said apparatus could readily be adapted to the determination, for example, of the partial thromboplastin time, or PTT, of the blood plasma samples to enable the use thereof for the more specific isolation of the factor or factors causing deficiencies in the clotting time of a patient's blood.
  • the apparatus of my invention may be utilized in the determination of the end point of a polymerization type reaction, the end point of which is evidenced by an abrupt change in viscosity, in a wide variety of liquids other and different than blood plasma samples.
  • the apparatus of the invention could be utilized to determine the end point of the flocculation reaction as would occur in pregnancy testing and/or the end point of the agglutination reaction as would occur in testing for rheumatoid arthritis.
  • the apparatus of the invention is applicable for such determination in reliable and accurate manner for blood plasma samples diluted down as far as 5 percent to thus enable the use of the apparatus to establish anti-coagulant dosage controls for essential therapeutic use.
  • reaction intensifying agent comprising a plurality of paramagnetic particles
  • reaction intensifying agent particles are of a material which is substantially chemically inert with regard to said fluid and said reagent, whereby said reaction intensifying agent will not interfere chemically with said reaction.
  • reaction intensifying agent is substantially opaque and generally uniformly distributed throughout said fluid-reagent-reaction intensifying agent mixture at the commencement of said reaction to render the same substantially turbid, and said reaction intensifying agent is operable to collect generally centrally of said fluid-reagent-reaction intensifying agent mixture under the influence of said activating means only at the completion of said reaction with concomitant change in the turbidity of said fluid-reagent-reaction intensifying agent mixture.
  • said means to mix a said fluid and said reagent with said reaction intensifying agent comprise, means to successively supply predetermined quantities of said reaction intensifying agent, means to successively mix a predetermined quantity of a said fluid with each of said reaction intensifying agent quantities, and means to successive-. sively mix a predetermined minimum quantity of said reagent with each of said reaction intensifying agent-fluid quantity mixtures to effect said reaction.
  • said means to successively supply said predetermined quantities of said reaction intensifying agent comprise, strip-like carrier means having said quantities disposed thereon in substantially equally spaced manner.
  • said carrier means are substantially transparent
  • said detecting means comprise light sensitive means which are operable to direct a beam of light through said mixture and through said carrier means to thereby detect said change in the turbidity of said fluid-reagent-reaction intensifying agent mixture through the detection of the attendant change in the light transmission characteristics thereof.
  • said means to mix a said fluid and said reagent with said reaction intensifying agent comprise, means to successively supply predetermined quantities of said reaction intensifying agent, means to successively mix a predetermined quantity of a said fluid with each of said reaction intensifying agent quantities, and means to successively mix a predetermined minimum quantity of said reagent with each of said reaction intensifying agent-fluid quantity mixtures to effect said reaction.
  • said means to successive sively supply said predetermined quantities of said means reaction intensifying agent comprise, strip-like carrier means having said quantities disposed thereon in substantially equally spaced manner.

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US881971A 1969-12-04 1969-12-04 Apparatus for the automatic determination of the coagulation, aggregation and or flocculation, or the like, rates of fluids, and novel reaction intensifying agent for use therewith Expired - Lifetime US3650698A (en)

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US27866D Expired USRE27866E (en) 1969-12-04 1972-12-14 Apparatus for the automatic determination op the coagulation, aggregation and/or fluocculation, or the like. rates of fluids, and novel reaction intensifying agent for use therewith

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US3861197A (en) * 1973-06-29 1975-01-21 Technicon Instr Method and apparatus for determining the viscosity of a liquid sample
US4062652A (en) * 1974-02-07 1977-12-13 Rolfo Fontana Gudrun B Reagent unit intended for microanalyses of standard type and device and method for its production
US4140401A (en) * 1977-09-22 1979-02-20 Paschal Richard C Cleaning apparatus and method
US4149405A (en) * 1977-01-10 1979-04-17 Battelle, Centre De Recherche De Geneve Process for measuring the viscosity of a fluid substance
US4201470A (en) * 1977-02-24 1980-05-06 Albrecht Ehrly Method and apparatus for measurement and registration of the aggregation rate of particles suspended in a liquid
US4477192A (en) * 1982-06-25 1984-10-16 Warner-Lambert Company Magnetic stirring apparatus and method
US4554088A (en) * 1983-05-12 1985-11-19 Advanced Magnetics Inc. Magnetic particles for use in separations
US4672040A (en) * 1983-05-12 1987-06-09 Advanced Magnetics, Inc. Magnetic particles for use in separations
US4676656A (en) * 1985-01-25 1987-06-30 Syntex (U.S.A.) Inc. Fluid handling apparatus and method
WO1988007666A1 (fr) * 1987-04-03 1988-10-06 Cardiovascular Diagnostics Inc. Element et procede permettant de realiser des analyses biologiques avec precision, rapidite et simplicite
WO1989010788A1 (fr) * 1988-05-10 1989-11-16 Cardiovascular Diagnostics Inc. Systeme d'analyse de coagulation employant des particules paramagnetiques
US4933088A (en) * 1986-07-11 1990-06-12 Kabushiki Kaisha Astec Method of and apparatus for treating water utilizing proton-releasing substance and/or magnetic field
US4935346A (en) * 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
US4950908A (en) * 1989-03-20 1990-08-21 Consolidation Coal Company Flocculant control system
US5069216A (en) * 1986-07-03 1991-12-03 Advanced Magnetics Inc. Silanized biodegradable super paramagnetic metal oxides as contrast agents for imaging the gastrointestinal tract
WO1992010754A1 (fr) * 1990-12-07 1992-06-25 Euro/Dpc Limited Procede et appareils d'analyse
EP0511189A2 (fr) * 1991-04-26 1992-10-28 MONSANTO p.l.c. Automatisation d'instruments d'éssai
US5174961A (en) * 1991-01-18 1992-12-29 Hemotec, Inc. High sensitivity coagulation detection apparatus
US5219554A (en) * 1986-07-03 1993-06-15 Advanced Magnetics, Inc. Hydrated biodegradable superparamagnetic metal oxides
US5314826A (en) * 1991-08-23 1994-05-24 Medtronic Hemotec, Inc. Platelet activation and function evaluation technique
US5460779A (en) * 1991-05-28 1995-10-24 Dade International Inc. Device for the automatic examination of blood samples
US5613491A (en) * 1994-06-14 1997-03-25 Ryder International Corporation Coagulation timer
US5925319A (en) * 1996-04-30 1999-07-20 Medtronic, Inc. Test cartridge for evaluating blood platelet functionality
US6284546B1 (en) 1994-06-16 2001-09-04 Dade Behring Marburg Gmbh Method and device for photodetection
US6458326B1 (en) 1999-11-24 2002-10-01 Home Diagnostics, Inc. Protective test strip platform
US6525330B2 (en) 2001-02-28 2003-02-25 Home Diagnostics, Inc. Method of strip insertion detection
US6541266B2 (en) 2001-02-28 2003-04-01 Home Diagnostics, Inc. Method for determining concentration of an analyte in a test strip
US20030082820A1 (en) * 2001-10-18 2003-05-01 Perbost Michel G.M. Chemical arrays
US6562625B2 (en) 2001-02-28 2003-05-13 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US20030180824A1 (en) * 2002-03-25 2003-09-25 Mpock Emmanuel C. System for performing blood coagulation assays and measuring blood clotting times
WO2005043156A1 (fr) * 2003-10-22 2005-05-12 Inverness Medical Switzerland Gmbh Detection de coagulation
US20050155415A1 (en) * 2003-12-17 2005-07-21 Boehringer Ingelheim Microparts Gmbh Process and device for determining viscosity
US20060016701A1 (en) * 2004-05-17 2006-01-26 Wei Qin Point of care heparin determination system
US20110263464A1 (en) * 2008-02-14 2011-10-27 Palo Alto Research Center Incorporated Enhanced drop mixing using magnetic actuation
US20120090726A1 (en) * 2010-10-15 2012-04-19 Leica Biosystems Nussloch Gmbh Method and Apparatus for Safety-Compliant Emptying and Filling of a Reagent Container
US20170089932A1 (en) * 2014-05-22 2017-03-30 Zafena Ab Assay to determine anticoagulants in blood or blood plasma
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US5526111A (en) * 1993-08-31 1996-06-11 Boehringer Mannheim Corporation Method and apparatus for calculating a coagulation characteristic of a sample of blood a blood fraction or a control
US5522255A (en) 1993-08-31 1996-06-04 Boehringer Mannheim Corporation Fluid dose, flow and coagulation sensor for medical instrument
US5841023A (en) * 1993-08-31 1998-11-24 Boehringer Mannheim Corporation Magnet for medical instrument
US5629209A (en) * 1995-10-19 1997-05-13 Braun, Sr.; Walter J. Method and apparatus for detecting viscosity changes in fluids
EP1815785A1 (fr) * 2006-02-02 2007-08-08 Bioception B.V.i.o. Dispositif en forme d'une cassette pour le diagnostic de fluides
CN106474997A (zh) * 2016-12-20 2017-03-08 广西师范大学 一种新型磁力搅拌棒
CN115839868B (zh) * 2022-10-27 2024-01-12 山东冽泉环保工程咨询有限公司 一种与靶向取样装置配套的反清洗头

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Cited By (80)

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US3861197A (en) * 1973-06-29 1975-01-21 Technicon Instr Method and apparatus for determining the viscosity of a liquid sample
US4062652A (en) * 1974-02-07 1977-12-13 Rolfo Fontana Gudrun B Reagent unit intended for microanalyses of standard type and device and method for its production
US4149405A (en) * 1977-01-10 1979-04-17 Battelle, Centre De Recherche De Geneve Process for measuring the viscosity of a fluid substance
US4201470A (en) * 1977-02-24 1980-05-06 Albrecht Ehrly Method and apparatus for measurement and registration of the aggregation rate of particles suspended in a liquid
US4140401A (en) * 1977-09-22 1979-02-20 Paschal Richard C Cleaning apparatus and method
US4477192A (en) * 1982-06-25 1984-10-16 Warner-Lambert Company Magnetic stirring apparatus and method
US4554088A (en) * 1983-05-12 1985-11-19 Advanced Magnetics Inc. Magnetic particles for use in separations
US4672040A (en) * 1983-05-12 1987-06-09 Advanced Magnetics, Inc. Magnetic particles for use in separations
US4676656A (en) * 1985-01-25 1987-06-30 Syntex (U.S.A.) Inc. Fluid handling apparatus and method
US5219554A (en) * 1986-07-03 1993-06-15 Advanced Magnetics, Inc. Hydrated biodegradable superparamagnetic metal oxides
US5069216A (en) * 1986-07-03 1991-12-03 Advanced Magnetics Inc. Silanized biodegradable super paramagnetic metal oxides as contrast agents for imaging the gastrointestinal tract
US4933088A (en) * 1986-07-11 1990-06-12 Kabushiki Kaisha Astec Method of and apparatus for treating water utilizing proton-releasing substance and/or magnetic field
US6887426B2 (en) 1986-08-13 2005-05-03 Roger Phillips Reagents test strip adapted for receiving an unmeasured sample while in use in an apparatus
US20030073151A1 (en) * 1986-08-13 2003-04-17 Roger Phillips Minimum procedure system
US4935346A (en) * 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
US20030073152A1 (en) * 1986-08-13 2003-04-17 Roger Phillips Minimum procedure system for the determination of analytes
US6881550B2 (en) 1986-08-13 2005-04-19 Roger Phillips Method for the determination of glucose employing an apparatus emplaced matrix
US20030054427A1 (en) * 1986-08-13 2003-03-20 Roger Phillips Minimum procedure system for the determination of analytes
US5304468A (en) * 1986-08-13 1994-04-19 Lifescan, Inc. Reagent test strip and apparatus for determination of blood glucose
US6268162B1 (en) 1986-08-13 2001-07-31 Lifescan, Inc. Reflectance measurement of analyte concentration with automatic initiation of timing
US6821483B2 (en) 1986-08-13 2004-11-23 Lifescan, Inc. Reagents test strip with alignment notch
US5179005A (en) * 1986-08-13 1993-01-12 Lifescan, Inc. Minimum procedure system for the determination of analytes
US5843692A (en) * 1986-08-13 1998-12-01 Lifescan, Inc. Automatic initiation of a time interval for measuring glucose concentration in a sample of whole blood
US5563042A (en) * 1986-08-13 1996-10-08 Lifescan, Inc. Whole blood glucose test strip
US6858401B2 (en) 1986-08-13 2005-02-22 Lifescan, Inc. Minimum procedure system for the determination of analytes
US6197494B1 (en) * 1987-04-03 2001-03-06 Cardiovascular Diagnostics, Inc. Apparatus for performing assays on liquid samples accurately, rapidly and simply
US20020119486A1 (en) * 1987-04-03 2002-08-29 Cardiovascular Diagnostics, Inc. Element and method for performing biological assays accurately, rapidly and simply
WO1988007666A1 (fr) * 1987-04-03 1988-10-06 Cardiovascular Diagnostics Inc. Element et procede permettant de realiser des analyses biologiques avec precision, rapidite et simplicite
US4849340A (en) * 1987-04-03 1989-07-18 Cardiovascular Diagnostics, Inc. Reaction system element and method for performing prothrombin time assay
JPH01502797A (ja) * 1987-04-03 1989-09-28 カーデイオバスキユラー・ダイアグノステイクス・インコーポレイテツド バイオアッセイを正確に、敏速に且つ単純に実施するためのエレメント及び方法
US5658723A (en) * 1987-04-03 1997-08-19 Cardiovascular Diagnostics, Inc. Immunoassay system using forced convection currents
JP2736091B2 (ja) 1987-04-03 1998-04-02 カーデイオバスキユラー・ダイアグノステイクス・インコーポレイテツド バイオアッセイを正確に、敏速に且つ単純に実施するためのエレメント及び方法
US5110727A (en) * 1987-04-03 1992-05-05 Cardiovascular Diagnostics, Inc. Method for performing coagulation assays accurately, rapidly and simply, using dry chemical reagents and paramagnetic particles
WO1989010788A1 (fr) * 1988-05-10 1989-11-16 Cardiovascular Diagnostics Inc. Systeme d'analyse de coagulation employant des particules paramagnetiques
AU633805B2 (en) * 1988-05-10 1993-02-11 Cardiovascular Diagnostics, Inc. Coagulation assay systems which utilize paramagnetic particles
US4950908A (en) * 1989-03-20 1990-08-21 Consolidation Coal Company Flocculant control system
WO1992010754A1 (fr) * 1990-12-07 1992-06-25 Euro/Dpc Limited Procede et appareils d'analyse
US5174961A (en) * 1991-01-18 1992-12-29 Hemotec, Inc. High sensitivity coagulation detection apparatus
EP0511189A2 (fr) * 1991-04-26 1992-10-28 MONSANTO p.l.c. Automatisation d'instruments d'éssai
US5309768A (en) * 1991-04-26 1994-05-10 Monsanto Company Automation of test instruments
EP0511189A3 (en) * 1991-04-26 1993-02-24 Monsanto P.L.C. Automation of test instruments
US5744098A (en) * 1991-05-28 1998-04-28 Dade International Inc. Device for the automatic examination of blood samples
US5460779A (en) * 1991-05-28 1995-10-24 Dade International Inc. Device for the automatic examination of blood samples
US5314826A (en) * 1991-08-23 1994-05-24 Medtronic Hemotec, Inc. Platelet activation and function evaluation technique
US5613491A (en) * 1994-06-14 1997-03-25 Ryder International Corporation Coagulation timer
US6284546B1 (en) 1994-06-16 2001-09-04 Dade Behring Marburg Gmbh Method and device for photodetection
US6955920B1 (en) 1996-04-30 2005-10-18 Medtronic, Inc. Test cartridge for evaluating blood platelet functionality
US5925319A (en) * 1996-04-30 1999-07-20 Medtronic, Inc. Test cartridge for evaluating blood platelet functionality
US6458326B1 (en) 1999-11-24 2002-10-01 Home Diagnostics, Inc. Protective test strip platform
US6979571B2 (en) 1999-11-24 2005-12-27 Home Diagnostics, Inc. Method of using a protective test strip platform for optical meter apparatus
US6562625B2 (en) 2001-02-28 2003-05-13 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US20030138356A1 (en) * 2001-02-28 2003-07-24 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US6541266B2 (en) 2001-02-28 2003-04-01 Home Diagnostics, Inc. Method for determining concentration of an analyte in a test strip
US7390665B2 (en) 2001-02-28 2008-06-24 Gilmour Steven B Distinguishing test types through spectral analysis
US6525330B2 (en) 2001-02-28 2003-02-25 Home Diagnostics, Inc. Method of strip insertion detection
US7300798B2 (en) * 2001-10-18 2007-11-27 Agilent Technologies, Inc. Chemical arrays
US20030082820A1 (en) * 2001-10-18 2003-05-01 Perbost Michel G.M. Chemical arrays
WO2003083489A1 (fr) * 2002-03-25 2003-10-09 Vector Ii, Inc. Systeme conçu pour realiser des dosages de coagulation sanguine et mesurer les temps de coagulation sanguine
US20030180824A1 (en) * 2002-03-25 2003-09-25 Mpock Emmanuel C. System for performing blood coagulation assays and measuring blood clotting times
US7235213B2 (en) 2002-03-25 2007-06-26 Farallon Medical, Inc. System for performing blood coagulation assays and measuring blood clotting times
WO2005043156A1 (fr) * 2003-10-22 2005-05-12 Inverness Medical Switzerland Gmbh Detection de coagulation
US20070158246A1 (en) * 2003-10-22 2007-07-12 Inverness Medical Switzerland Gmbh Coagulation detection
US7357016B2 (en) 2003-12-17 2008-04-15 Boehringer Ingelheim Microparts Gmbh Process and device for determining viscosity
US20050155415A1 (en) * 2003-12-17 2005-07-21 Boehringer Ingelheim Microparts Gmbh Process and device for determining viscosity
US8801918B2 (en) 2004-05-17 2014-08-12 Medtronic, Inc. Point of care heparin determination system
US7699966B2 (en) 2004-05-17 2010-04-20 Medtronic, Inc. Point of care heparin determination system
US20100181210A1 (en) * 2004-05-17 2010-07-22 Wei Qin Point of Care Heparin Determination System
US20060016701A1 (en) * 2004-05-17 2006-01-26 Wei Qin Point of care heparin determination system
US20110263464A1 (en) * 2008-02-14 2011-10-27 Palo Alto Research Center Incorporated Enhanced drop mixing using magnetic actuation
US8617899B2 (en) * 2008-02-14 2013-12-31 Palo Alto Research Center Incorporated Enhanced drop mixing using magnetic actuation
US9016332B2 (en) * 2010-10-15 2015-04-28 Leica Biosystems Nussloch Gmbh Method and apparatus for safety-compliant emptying and filling of a reagent container
US20120090726A1 (en) * 2010-10-15 2012-04-19 Leica Biosystems Nussloch Gmbh Method and Apparatus for Safety-Compliant Emptying and Filling of a Reagent Container
US10739239B1 (en) * 2013-10-28 2020-08-11 Ifirst Medical Technologies, Inc. Rotating magnetic disc medical analyzer and coagulation profiler
US10823743B1 (en) * 2013-10-28 2020-11-03 Ifirst Medical Technologies, Inc. Methods of measuring coagulation of a biological sample
US11598707B1 (en) 2013-10-28 2023-03-07 Ifirst Medical Technologies, Inc. Medical analyzer and coagulation profiler
US11788941B1 (en) 2013-10-28 2023-10-17 Ifirst Medical Technologies, Inc. Method of using disposable BioMEMS coagulation profiling cartridge
US12203833B1 (en) 2013-10-28 2025-01-21 Ifirst Medical Technologies, Inc. Medical analyzer and coagulation profiler with tracked oscillating disc
US12203834B1 (en) 2013-10-28 2025-01-21 Ifirst Medical Technologies, Inc. Disposable BioMEMS coagulation profiling cartridge with a tracked oscillating disc
US20170089932A1 (en) * 2014-05-22 2017-03-30 Zafena Ab Assay to determine anticoagulants in blood or blood plasma
US10613104B2 (en) * 2014-05-22 2020-04-07 Zafena Ab Assay to determine anticoagulants in blood or blood plasma

Also Published As

Publication number Publication date
CA959741A (en) 1974-12-24
GB1340829A (en) 1973-12-19
DE2058973B2 (de) 1974-07-11
DE2058973A1 (de) 1971-06-16
BE759811A (fr) 1971-06-03
CH561422A5 (fr) 1975-04-30
NL7016252A (fr) 1971-06-08
DE2058973C3 (de) 1975-02-27
USRE27866E (en) 1974-01-01
FR2072819A5 (fr) 1971-09-24
GB1325730A (en) 1973-08-08

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