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Publication numberUS3635678 A
Publication typeGrant
Publication dateJan 18, 1972
Filing dateJun 13, 1969
Priority dateJun 13, 1969
Publication numberUS 3635678 A, US 3635678A, US-A-3635678, US3635678 A, US3635678A
InventorsBowen John G, Seitz Lamont J
Original AssigneeBaxter Laboratories Inc
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Clot-timing system and method
US 3635678 A
Abstract
A system and method is provided which has the general capabilities of measuring the speed of coagulation, congealing or solidification of a fluid sample, and which has particular utility in the measurement of the time required by a sample under test to increase viscosity to a particular level. The system and method to be described is predicated on a viscosity principle, and it includes a member suspended in the fluid sample and which changes position when the sample achieved a predetermined degree of viscosity. The change in position of the aforesaid member is sensed, and the time at which the change occurs, is used in the determination of the time required, for example, for the sample to form a fibrin clot, in a blood or plasma sample or to effect a particular reaction causing solidification or congealing of the sample.
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Description  (OCR text may contain errors)

United States Patent Seitz et a].

[ 1 Jan. 18,1972

CLOT-TIMING SYSTEM AND METHOD 3,267,363 8/1966 Young ..23/253 X [72] inventors: Lamont J. Seitz, Huntington Beach, Calif.; 337L112 9/1966 et a1 "23,253 h G B d m 3,375,705 4/1968 Kim ..73/57 e 3,443,419 5/1969 Gruitroy et al. ...73/64.1 3 Assignee; Baxter Laboratories, Inc, Morton Grove, 3,520,659 7/1970 Steinberg et al. ..23/253 X lll.

Primary Examiner-Joseph Scovronek [22] Flled: June 1969 Attorney-Walter C. Kehm and Robert G. Pollock 2| A LN 846,992 l 1 PP 57 ABSTRACT Related Application Data A system and method is provided which has the general capa- 3 continuatiomimpan f Sen 733332 J 7 bilities of measuring the speed of coagulation, congealing or 1963, abandone solidification of a fluid sample, and which has particular utility in the measurement of the time required by a sample under 52 vs. Cl. ..23/230 R, 23 230 B, 23/253, test to increase viscosity w a Particular level The System and 23/259, 73/57, 73/64. I, 206/47 A, 250/218, method to be described is predicated on a viscosity principle, 250/222, 335/205, 356/39, 356/72 and it includes a member suspended in the fluid sample and 51, int. Cl. ..Lcoin 11/16, G0ln 33/16, HOlh 9 00 which. Changes Position when the Sample achieved a predeter- [58] Field of Search ..23/230, 230 B, 253, 259; mined deg'ee The change P of 73/54 64A 356/39. 250 21 222. 20 4 7 A aforesaid member iS sensed, and the time at WhiCh the change occurs, is used in the determination of the time required, for [56] References Cited example, for the sample to form a fibrin clot, in a blood or plasma sample or to effect a particular reaction causing UN E STATES PATENTS solidification or congealing of the sample. 2,957,338 10/1960 Kennedy et al ..73/54 40 Claims, 8 Drawing Figures 7r/ M rm? Qee/ 5d Ji- PATENTED JAN-18872 3,635,678

SHEET 1 UF 3 May/13 96 54% .j

PATENIEB JAN 1 am I SHEET 2 OF 3 CLOT-TIMING SYSTEM AND METHOD This application is a continuation-in-part of copending US. Pat. application Ser. No. 738,382, filed June 17, 1968, now abandoned.

BACKGROUND OF THE INVENTION The importance of blood coagulation has long been recognized. In recent years, there has been a large amount of research into the complexities of coagulation. Much of the present interest in coagulation has been centered upon the disease of hemophilia and other congenital bleeding disorders.

Before proper therapy can be initiated for a bleeding disorder in the patient, the cause of the bleeding must first be understood. These causes can be determined by different tests involving the coagulation of the patients blood. These tests involve, for example, the determination of the time required by the patient's blood to manifest a clotting condition.

In the past, the incidence of clotting of the blood sample was usually detected by visual means. However, instruments for automatically detecting the clot formation have also been proposed in the prior art. These instruments, for example, detect the clot formation in the blood or plasma sample by photometric means, or by resistance or capacitance changes in an electric circuit. However, the prior art systems for the most part suffer from one drawback or another. For example, most of the prior art instruments have questionable temperature control, and have time resolutions no better than 0.6 seconds. In addition, the usual prior art instruments are rather inconvenient to use, since they require frequent cleaning, adjustments, and the like.

In other reactions where the time of congealing or solidification is of interest, the conventional viscosimeter is used to detect and measure a reaction rate or time to reach a certain viscosity. These, however, are usually not as uniform or precise as are required in sensitive reactions as for instance in polymerization reactions, precipitation of viscous components of solutions, or in other diagnostic tests in which there is a sudden or dramatic increase in viscosity. The conventional tests now in use suffer from the same problems extant with the clottiming tests mentioned above.

The improved timing system and method of the present invention, as mentioned briefly above, detects in a predetermined manner any increase in clotting in a blood or plasma sample by sensing predetermined changes in the viscosity of the sample. In the embodiment to be described, for example, a ball composed of appropriate magnetic material, such as steel, is introduced into the sample. A magnetic field is provided through the sample which tends to hold the magnetic ball in a fixed position as the sample is reciprocated. This condition obtains so long as the viscosity of the sample remains below a predetermined threshold. However, when the increased viscosity of the fluid sample is sufficient to enable the reciprocating fluid to move the ball away from its fixed position, and against the magnetic force tending to hold it in its fixed position, the change in the ball location in the sample is detected and the time can be measured by any convenient means.

The resultant movement of the ball can be sensed by photoelectric means, as will be described. As an alternative, the ball movement may be detected by sensing the resulting change in magnetic reluctance of the system as the ball is so moved. In either event, the precise time for the reaction in the sample to thicken, congeal or solidify can be measured by the apparatus of the invention. It will be appreciated, of course, that the sample itself may be held stationary, and the magnetic field moved back and forth to achieve the same result.

The system, apparatus and method to be described is advantageous in that tests may be conducted in conjunction with disposable test tubes of the samples, each containing a magnetic ball. The test tubes may be held at a predetermined temperature in the apparatus of the invention, before and when the actual test is made. After each test, the test tube, its magnetic ball, and the remaining contents in the tube may all be disposed of so that there are no cleaning operations involved.

In the clot-timing test as described, a precisely controlled heating system is preferably used in the apparatus, so that the temperature may be held, for example, at normal body temperature of 37 C. 0.5 for blood or plasma tests. The apparatus to be described also inherently provides adequate mixing of the sample during the test. For precise time measurements, the start of the time interval is automatically synchronized with the moment the test is initiated. A constructed embodiment of the apparatus of the invention exhibits capabilities of providing time resolutions to 0.l second, and a detection sensitivity down to 5 percent activity.

Many factors interact in a complex manner in the blood or plasma sample from the first step in the coagulation process to the final formation of the fibrin clot. The coagulation process itself undergoes three separate stages, for example. During the first stage, several plasma factors react with platelets in the presence of a source of calcium ions, such as calcium chloride, to generate thromboplastin. The second stage involves the conversion of prothrombin to thrombin. Once formed, the process enters the third stage during which the thrombin rapidly converts soluble fibrinogen to insoluble fibrin. In so doing, the thrombin catalyzes the spreading of fibrinopeptides from the fibrinogen molecule, allowing the latter to polymerize and form the fibrin clot.

Any source of soluble ionizable calcium salts are suitable as the aforesaid source of calcium ions in the clot timing technique of this invention. Calcium chloride is preferred by most researchers but others prefer other soluble ionizable calcium compounds but care must be exercised as for instance the oxalate salt is insoluble and not ionizable and the citrate salt is, for example, not ionizable even though soluble.

In making coagulation tests, the first stage may be bypassed by adding tissue thromboplastin and calcium chloride to the blood or plasma sample. Such tests measure the prothrombin time of the sample. The original one-stage prothrombin time test was devised by Quick (Amer. .loum. Clin. Pathol. 10, 222, 1940). This test was originally believed to measure prothrombin activity only. It has since been found that the Quick test actually measures all the factors involved in the latter coagulation stages described in the preceding paragraph. Nevertheless, the Quick test has proven to be still a useful tool in evaluating anticoagulant therapy. However, if prothrombin is to be measured specifically, a two-stage test is used in which prothrombin-free plasma is added to the sample, in the method described by Ware and Seegers, Amer. Jour. Clin. Pathol. 19,471 (1949).

The system, method and apparatus of the present invention may be used in conjunction with either of the aforesaid tests, or in other tests involving fluid viscosity. For example, in addition to the Quick test referred to above, in which liquid thromboplastin forms the additional reagent, the system, apparatus and method of the invention can also be applied to the PTT" test involving kaolin-activated liquid partial thromboplastin; the differential PTT" test involving AHF reagent, PTC reagent, and kaolin activated liquid partial thromboplastin; the modified Owren test involving prothrombin-free beef plasma and liquid thromboplastin; the factor VIII Al-IF) assay involving kaolin-activated liquid partial thromboplastin, factor VIII deficient substrate, and a diluting fluid such as veronal buffer; and the factor IX (PTC) assay involving kaolin-activated liquid partial thromboplastin, factor IX deficient substrate, and a diluting fluid such as veronal buffer, as are described by Biggs and MacFarlane in Human Blood Coagulation and its Disorders, Third Edition, F. A. Davis Company, Philadelphia, Pa. 1962).

All the aforesaid tests may involve the start of the time measurement as the calcium chloride solution is added. The strength of the calcium chloride solution, however, may differ from test to test, for example, 0.02 molar to 0.03 molar. For each of the tests, for example, the test tubes of the suitable reagent are provided, each incorporating a magnetic ball. The blood or plasma samples to be tested are pipetted into the test tubes containing the suitable reagent after the test tubes have been placed in the apparatus, and are then incubated at the test temperature. The test in each instance is started by the addition of the calcium chloride solution, and the apparatus to be described herein is constructed so that the timer starts at the exact moment the calcium chloride is pipetted into the sample. The timer is subsequently stopped by the change of viscosity in the sample, for example, due to the first appearances of strands of fibrin clot.

In the actual test to be described, the prothrombin time of a combination of blood plasma, calcium ions and thromboplastin is measured. The presence of calcium ions, either as calcium chloride or other ionizable and soluble calcium salt is essential to the clotting action in the particular test, as measured by the apparatus. There is an optimum concentration of calcium ions to give the shortest and most accurate clotting time. This is normally one-fortieth molar as standardized with Ice. of 3.8 percent sodium citrate solution and 9 milliliters of whole blood. As mentioned above, in the specific embodiment of the invention to be described, the thromboplastin is prepackaged as a disposable item in a test tube, complete with a magnetic ball and stopper, for each blood or plasma test. The blood sample of the patient is initially mixed with the thromboplastin in the test tube. However, the calcium chloride ingredient is omitted from the prepackaged thromboplastin, and the calcium chloride solution is pipetted into the test tube at the initiation of the test. The fibrin clot is sub sequently detected by means described above, at which time the timer stops and provides an indication of the prothrombin time. In some instances, of course, the calcium chloride may be included in the prepackaged thromboplastin. Moreover, in some laboratories, the thromboplastin may be carried as a stable item, and introduced into the test tube and magnetic ball combination in the laboratory itself, just prior to making the tests.

While we have described this apparatus and the method as having particular utility in the prothrombin or clotting times of blood, its ready application to other tests is obvious to those having particular requirements for measuring the precise time for a particular reaction to occur which is characterized by an increase in viscosity of the sample to a point where the viscosity is sufficient to jell, congeal, or thicken the sample enough to move the magnetic ball out of its predetermined position in the magnetic field as the sample vial is reciprocated relative to the field.

In jell time measurements for example, and in polymerization action or tests, the same basic principle is employed, and any particular combination of reagents or conditions can be employed as are conventional in that test with only the clearance between the magnetic ball and the sample holder being considered in relation to the intensity or speed of the viscosity increase of the reaction or physical phenomena being measured. In some reactions, for example, additional polymerization reactions or jell formation can take place with such a dramatic increase in viscosity that gross clearance can be provided between the magnetic ball and the wall of the sample holder because the ball will become almost imbedded and immobile in the sample that clearance is immaterial. In other reactions however, there may be desired a close tolerance between the walls of the sample holder and the ball such that a precise viscosity is necessary for the ball to be moved out of its predetermined location in the magnetic field. Thus each specific test may require a different clearance or at least consideration of the normal viscosity increase incident so that test and a selection of the most optimum clearance for that test. In the following discussion, clearance will be considered relative to the clot-timing test.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. I is a perspective schematic representation showing the principles upon which the embodiment of the invention to be described is predicated;

FIG. 2 is a perspective view of the apparatus of the invention, in somewhat schematic form, and representing one embodiment;

FIG. 3 is a prepackaged test tube magnetic member assembly in which the reagent for the sample to be tested is contained;

FIG. 4 is an enlarged fragmentary section of a portion of the apparatus of FIG. 2 and showing the photoelectric sensing system which is used in the apparatus of FIG. 2;

FIG. 5 is an elevational view of a suitable pulse generator which can be used in conjunction with the apparatus of FIG. 2;

FIG. 6 is a diagram of the electrical control system associated with the apparatus of FIG. 2; and

FIGS. 7 and 8 show an appropriate housing for the rap paratus, the housing being shown closed in FIG. 7 and open in FIG. 8.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENT As shown in FIG. 1, a test tube 10 containing the fluid to be tested is supported in the apparatus on a piston, or cam shaft, 12. The piston 12 moves reciprocally in the vertical direction in FIG. 1, so that the test tube 10 is moved up and down with the piston. In carrying out the concepts of the present invention, a magnetic field is established through the test tube. This magnetic field may be created by means, for example, of a pair of stationary bar magnets 14 and 16. A magnetic member 18 is suspended in the fluid within the test tube 10. This member may, for example, be in the form of a ball of stainless steel, or other appropriate magnetic material. For example, the ball may be a chromium-plated member whose interior is formed of an appropriate magnetic material. In a constructed embodiment of the invention, the magnetic member 18 has the configuration of a stainless steel ball, and a diameter of 0. I87 inches. The test tube 10, on the other hand, is a precision bore test tube in the constructed embodiment, whose bore diameter is 0.l99 inches i 0.004 inches. The excursion rate of the test tube by the piston 12 in the constructed embodiment is complete cycles per minute, and the excursion amplitude is controlled so that the ball moves relative to the liquid in the test tube a maximum amount without breaking the surface of the liquid. Should the ball break through the meniscus at the surface of the liquid, air is entrained within the liquid and bubbles are formed.

It will be appreciated that so long as the viscosity of the liquid in the test tube is below a predetermined threshold, the magnetic member 18 will be held stationary by the magnetic field established by the magnets 14 and 16, as the liquid moves up and down with the test tube 10. However, when the viscosity of the liquid exceeds a certain threshold due, for example, to the formation of a fibrin clot, the liquid will draw the magnetic member 18 with it out of the magnetic field, and against the force of the magnetic field. The resulting change in the position of the magnetic member 18 can be sensed by directing a light beam through the test tube from a light source 20, the light beam being detected by a photocell 22 when the magnetic member 18 moves its position.

That is, the light source 20 and photocell 22 may be mounted in the same plane as the magnets 14 and I6, and disposed at right angles thereto, as shown in FIG. I. So long as the magnetic member 18 is held in the magnetic field established by the magnets 14 and 16, it blocks the light to the photocell. However, when the viscosity of the fluid in the test tube exceeds the predetermined threshold, the magnetic member 18 is moved from its illustrated position, so that the light from the source 20 may strike the photocell 22, causing the photocell to generate a signal.

The concept shown in FIG. 1 permits prothrombin times conveniently to be determined in blood or plasma samples. For example, the test tube 10 may be disposable, together with its magnetic member 18. Initially, a quantity of thromboplastin is inserted into the test tube, of the order, for example, of one-tenth milliliter. The tube is then equipped with a stopper. Before the test, the stopper may be removed and an equal quantity of blood or plasma sample, for example, may be pipetted into the test tube. Then, at the instant the timing interval is initiated, a like amount of calcium chloride solution may be introduced into the test tube to start the coagulation reaction. During the test, the magnetic member 18 moves relative to the liquid in the test tube, from the bottom of the liquid to the meniscus, for example, as the test tube is moved. In this way, the magnetic member 18 additionally performs a thorough stirring function. The test tube, ball and stopper are shown in FIG. 3, the stopper being designated as 36.

The subsequent movement of the magnetic member 18 out of the magnetic field upon the formation of the fibrin clot, causes the photocell 22 to generate an output, and this output may be used to terminate the timing interval, so that the prothrombin time may be determined. As mentioned above, as an alternative, the movement of the magnetic member 18 relative to the liquid may be detected by measuring the resulting change in reluctance in the magnetic circuit, rather than by the photocell 22, if so desired. Also, although a reciprocal motion is shown in the drawing and described above, other suitable motion of the liquid, such as a circular movement, for example, may be used with respect to the ball 18.

Appropriate apparatus for carrying out the concept shown in FIG. 1 is illustrated in FIG. 2. The apparatus of FIG. 2 includes, for example, a metallic block 30. An electric heater and thermostat unit 32 is inserted into the block 30, and when the heater is energized, the thermostat unit serves to cause it to maintain the block at a predetermined temperature. This temperature of plasma and blood tests, for example, is preferably 37 C. which corresponds to the normal body temperature. The control may be sufiiciently precise so that the block is maintained at that temperature to within 0.5 C.

A series of incubation wells 34 may be provided in the block 30, and these wells may serve as an appropriate storage means for test tubes of the samples to be tested, and also as a storage means for a test tube of the calcium chloride solution which is used in the tests, as described above, since it too should be maintained at the test temperature. For example, prior to the initiation of the test, a group of prepackaged test tubes 10, shown in FIG. 3, each containing its magnetic ball 18 and stopper 36, and each filled with, for example, one-tenth of a milliliter of thromboplastin, may be removed from a refrigerator and placed in the incubation well 34.

The different blood samples to be tested may then be pipetted into the various test tubes in the wells 34, with onetenth of a milliliter being placed in each test tube. The test tubes are left in the incubation wells for a sufficient incubation interval so that the liquids therein may be brought to the test temperature of 37 C. In a typical test, for example, and as mentioned above, it is usual for each test tube to contain one tenth of a milliliter of plasma, one-tenth of a milliliter of thromboplastin, and subsequently one-tenth of a milliliter of calcium chloride solution added to initiate the test.

When a test is to be made, one of the test tubes is removed from its incubation well 34 and is placed in a further well 40 which extends through the block 30. The aforesaid piston, or reciprocating camshaft, I2 is positioned in the well 40, and the shaft rests on the edge of an eccentrically mounted cam 42. The cam 42 is driven, for example, by an electric motor 44. It will be appreciated that when the electric motor 44 is energized to drive the eccentric cam 42, the cam shaft 12 is caused to move up and down in the well 40. Then, when a test tube 10 is inserted down into the well, it rests on top of the shaft 12 in the manner shown in FIG. 1, for example, to move with the shaft up and down in the well 40.

The magnets 14 and 16, together with the light source and photo cell 22, are mounted in appropriate tunnels in the block 30. These tunnels may have the configuration shown in FIG. 4, for example, with respect to the photo cell 22 and light source 20, the latter being formed by an electric lamp. The diameter of the tunnels from the photo cell and light source are preferably made slightly smaller than the diameter of the magnetic member 18, so that slight movements of the magnetic member will not cause the photo cell to be activated. For example, in the construction embodiment, the tunnels have a diameter of one-eighth of an inch, whereas the magnetic member 18, or ball has a diameter, as mentioned above, of 0.187 inch.

The electrical control system of the apparatus may be such that immediately upon the placement into the well 40 of the test tube containing the sample to be tested and containing the magnetic member 18, the resulting blocking of the light beam incident on the photocell 22 by the ball causes the electric motor 44 to be activated, so that the test tube moves up and down in the well 40. However, the coagulation reaction does not begin until the calcium chloride solution is added to the liquid in the test tube. This calcium chloride solution addition maybe made, for example, by means of a flexible pipette tube 50 which, for example, may be activated by a pipette mechanism 52. The pipette mechanism 52 may be similar to that described in US. Pat. No. 3,236,423. It comprises essentially an outer cylinder 54 and an inner rod 56. The rod 56 is mounted on a base 60, and the cylinder 54 is mounted over the rod in coaxial relationship therewith. A spring 62, for example, biases the cylinder into an upper position. The tube 50 is coupled into the interior of the cylinder 54 through the upper end of the cylinder.

The outer cylinder 54 is first pressed down to a predetermined position, established by an appropriate stop rod (not shown), and the free end of the flexible tube may be inserted into the test tube which contains the calcium chloride, and which may be stored in one of the incubation wells 34. The cylinder 54 is then released causing a precisely metered amount of the calcium chloride solution to be drawn into the cylinder 54. Then, the free end of the flexible tube 50 is moved over the top of the test tube 10 which is moving reciprocally in the well 40, and the cylinder 54 is moved down to the base 60 against the bias the spring 62. This latter movement of the cylinder causes the calcium chloride solution to be discharged from the cylinder 54 into the reciprocating test tube in the well 40. At the same time, a stop 64 on the rim of the cylinder 54 aetuates a microswitch 66 by engaging its operating arm 66a. The microswitch is used to start the timing mechanism which times the coagulation period, the reaction being started by the insertion of the calcium chloride solution into the sample under test.

If so desired, the pipette assembly described in copending application of Seitz and Jerg, Ser. No. 775,252, filed Nov. 13, 1968, now US. Pat. No. 3,498,135, may be used. Also, the guide mechanism to be described in conjunction with FIG. 9 is convenient in pennitting the end of the pipette to be properly placed over the top of the reciprocating test tube in the well 40.

It will be appreciated that while a sample is being tested, the magnetic member 18 efiectively moves up and down through the sample, as mentioned above. The apparatus may be designed so that the movement of the magnetic member during the test extends from near the bottom of the test tube in the well to near the meniscus at the top of the fluid in the test tube. In this manner, and as pointed out previously herein, the magnetic member 18 also performs a mixing function, so that the liquids in the test tube are intimately mixed during the test. This mixing feature is especially important in certain tests referred to above involving, for example, kaolin. Kaolin is held in suspension in the liquid for certain tests, and it has a tendency to precipitate to the bottom of the test tube, this tendency being prevented by the mixing function established by the magnetic member.

The apparatus of the invention, in the embodiment under consideration, includes a simple known type of impulse counter which serves to record the prothrombin time during each sample test. The pulses for the counter may be conveniently generated by a pulse generator such as shown in FIG. 5. This pulse generator includes, for example, a simple magnetic reed switch which is mounted on a base 102 by means, for example, of a pair of posts 104 and 106. A motor 108 is mounted under the base 102, and a drive shaft 1 10 from the motor extends through the base. A turntable 112 is supported on the upper end of the drive shaft under the reed switch 100, and a bar magnet 114 is mounted on the turntable adjacent the reed switch 100.

The field from the bar magnet 114 is such that the contacts of the reed switch are closed each time the bar magnet is disposed parallel to the longitudinal axis of the switch. This occurs twice for each revolution of the turntable 112. Therefore, there are two closures of the magnetic read switch 100 for each revolution of the turntable 112. The turntable may be turned, for example, by the motor 108 at 300 rpm. This means that there are closures of the reed switch 100 per second, so that the pulse generator generates 10 pulses per second. These pulses are generated by completing the circuit between the terminals 100a and 10% of the reed switch. The resulting generator represents an inexpensive mechanism, yet one which is precise and accurate.

For example, the motor 108 may be a synchronous motor, so that the repetition frequency of the pulses generated by the pulse generator is synchronized with the alternating current line frequency of the alternating current mains, and which is held precisely constant. Also, the reed switch 100 may be controlled, so that the pulse generator generates 10 pulses per second, as mentioned above, so that the timing intervals may be timed with a resolution down to one-tenth of a second.

Referring now to the electrical diagram of FIG. 6, the circuit has a pair of input terminals 200 which are intended to be connected to the usual I l5-volt alternating current mains. An appropriate neon-indicating lamp and a series resistor 204 are connected across the terminals 200, the lamp 202 indicating when the circuit is energized.

The alternating current leads from the input terminals 200 are connected to the primary winding of a transformer 206. The transformer 206 serves to reduce the line voltage down to 24-volts AC. The aforesaid light source 20 is connected across the secondary winding of the transformer 206. A bridge rectifier, made up of a group of diodes CR1, CR2, CR3, CR4 is connected to the secondary of the transformer 206, and this rectifier provides full wave rectification of the alternating current, so as to establish 30-volts DC between the lead 208 and the grounded lead 210. A SOO-microfarad microfarad filter capacitor C1 is connected across the leads.

The aforesaid heater 32 is connected through a usual thermostatic switch 212 across the 115 volt leads from the input terminals 200. A capacitor C2 of, for example, 0.0l microfarads, is connected between one of the aforesaid leads and the junction of the switch 212 and heater 32 to protect the contacts of the thermostatic switch. A neon indicator lamp 214 and series resistor 216 are connected across the heater 32, and this lamp glows whenever current is actually flowing through the heater. The indicator lamp 214 provides an indication as to when the block 30 of FIG. 2 has been brought up to operating temperature, at which time the lamp is extinguished.

The output of the photo cell 22 is introduced to a photo cell amplifier 217 which is made up of a pair of NPN-transistors 218 and 220. The photo cell is connected between the lead 208 and the base of the transistor 218. A 5 kilo-ohm potentiometer 222 connects the base of the transistor 218 to the grounded lead 210. This potentiometer may serve as a sensitivity adjustment for the output from the photo cell. The collector of the transistor 218 is connected to the junction of a kilo-ohm resistor 224 and an 820 ohm resistor 226. The resistor 224 is connected to the base of the transistor 220, whereas the resistor 226 is connected to the lead 208.

The base of the transistor 220 is connected to a 6.8 kiloohm resistor 228, whereas the emitter of the transistor 220, together with the emitter of the transistor 218, are connected to a 180 ohm resistor 230. The resistors 228 and 230 are both connected to the grounded lead 210. The collector of the transistor 220 is connected throughthe operating coil of a relay K1 to the positive lead 208. A diode CR5 is connected across the winding, and this diode serves to suppress the inductive transient from the relay winding and serves to protect the transistor 220.

The relay K1 has a pair of lower normally open contacts and a pair of upper normally open contacts. The lower normally open contacts are connected to the lead 208 and relay coil K1 on one hand, and to the lower movable contacts of a relay K2 and to the start switch 66 on the other hand. It will be remembered that the start switch 66 is the microswitch of FIG. 2, and that this switch is closed the moment the calcium chloride is added to the liquid in the test tube to initiate the test. One side of the coil of the relay K2 is connected to the lower contacts and to the switch 66, and the other side of the coil of the relay K2 is grounded.

The upper contacts of the relay K1 are interposed in one of the alternating current leads from the input terminals 200 and to one terminal of each of the motors 44 and 108. The other terminal of each of these motors is connected to the other alternating current lead. Therefore, when the upper contacts of the relay K1 close, both the motors 44 and 108 are energized.

The upper contacts of the relay K2, on the other hand, when closed, serve to complete a connection to an impulse counter 250 which is in series with the magnetic reed switch 100, the other side of the impulse counter being connected to the positive lead 208. The impulse counter 250, for example, may be any known type of electromechanical counter having a numbered scale, and which provides a decimal reading of the number of pulses applied to it. The counter is preferably equipped with an appropriate reset lever. A diode CR6 is then connected across the impulse counter 250 to suppress inductive transients and to protect the reed switch 100.

When one of the test tubes 10 containing the magnetic ball 18 is dropped into the well 40 of the block 30 in FIG. 2, the ball is originally held by the magnets 14 and 16 between the light source 20 and the photo cell 22. This causes the resistance of the photo cell 22 to increase which, in turn, causes the photo cell amplifier 217 to energize the relay Kl. When the relay K1 is energized, the closure of its normally open upper contacts energizes both the motors 108 and 44. Therefore, the moment the test tube is dropped into the well 40, the reciprocating motor 44 is energized and the test tube begins to move up and down in the well. In addition, the pulse generator motor 108 is energized at this time, so that the reed switch is opened and closed at the rate, for example, of 10 closures per second. However, since the relay K2 is now deenergized, the pulses generated by the reed switch 100 are not counted by the impulse counter 250. e

The moment the calcium chloride is introduced into the test tube in the well 40 to initiate the test, the switch 66 on the pipetting apparatus is closed momentarily. This causes the relay K2 to be energized through the lower closed contact of the relay K1. The lower contacts of the relay K2 now act as holding contacts, so that the relay K2 is held energized. So long as the relay K2 is energized, its upper contacts permit the pulses from the reed switch'100 to be passed to the impulse counter 250, so that the impulse counter performs a count of the said pulses.

The impulse counter 250 continues to count the pulses until the coagulation of the sample in the test tube moving up and down in the well 40 draws the ball 18 out of the magnetic field and out of the light beam from the source 20 to the photo cell 22. When this occurs, the relay Kl becomes deenergized. This breaks the holding circuit to the relay K2, so that the relay K2 also becomes deenergized. Therefore, the pulses from the reed switch 100 are no longer applied to the impulse counter 250, and the impulse counter is stopped, thereby providing a reading of the prothrombin time.

As mentioned above, the apparatus of the invention may be housed in a casing such as shown in FIGS. 7 and 8. The block 30 is shown in FIGS. 7 and 8 with its incubation wells 34. Also the test well 40 is provided in the top of the block. The impulse counter 250 is mounted so that its scale can be viewed through the case. A lever 250a may be provided for resetting the impulse counter scale back to zero, when so desired.

As mentioned above, the pulses from the pulse generator switch 100 permit the impulse counter 250 to provide decimal readings to one-tenth of a second. The neon indicator 214 is mounted adjacent the impulse counter, and as also explained, this indicator is extinguished when the block has been raised to the test temperature. The indicator lamp 202 is also provided to the right of the housing to indicate when the power is applied. An appropriate on-off" toggle switch is mounted adjacent the indicator 202 to constitute the power switch for the unit.

A pipette mechanism 300, different from that described above, may be provided for adding the calcium chloride to the solution so as to initiate each test. This mechanism, for example, may be turned to a position over the well 40, at which time a measured quantity of calcium chloride is introduced into the moving test tube in the well 40, and the timer circuit is simultaneously started by closing a switch, such as the switch 66 in FIGS. 2 and 6, as described above.

Ancillary equipment such as pipettes and disposable tips, and the like, may be stored in a compartment formed in the rear of the casing, as shown in the view of FIG. 8. As mentioned above, instead of the pipette mechanism 300, the pipette described in copending application of Seitz and Jerg, Ser. No. 775,252, filed Nov. 13, 1968, now U.S. Pat. No. 3,498,135, may be used to introduce the calcium chloride into the movable test tube in the well 40.

As mentioned above, the advantages and features of the apparatus, system and method of the present invention include the provision of a relatively inexpensive unit and method which may be operated easily and by semiskilled personnel, and yet which is capable of quickly and accurately providing precise prothrombin time measurements, and the like. A major advantage of the apparatus described from an opera tional standpoint, is the fact that all the samples may be tested in disposable test tubes, so that there is no mess and no cleanup required after each test. The pipettes which are used to insert the blood or plasma samples into the test tubes, and which may be used to introduce the calcium chloride, may be equipped with removable tips, which can be discarded after each use.

The invention provides, therefore, an improved clot timer method, system and apparatus which operates on a viscosity principle, and which can be used in general, wherever viscosity levels above predetermined thresholds are to be sensed and/or corresponding time intervals for the test fluids to undergo viscosity changes are to be measured.

What is claimed is:

1. Apparatus for sensing changes in viscosity of a fluid sample including: a receptacle means for the fluid; a magnetic member suspended in the fluid in the receptacle; magnetic means for creating a magnetic field in the receptacle for holding said magnetic member in a predetermined position with respect to said magnetic field so long as the viscosity of said fluid is below a predetermined threshold and in the presence of relative movements between said fluid and said magnetic field; means coupled to at least one of the aforesaid means for imparting relative movement between said receptacle and said magnetic field; and means for sensing movements of said magnetic member away from said predetermined position in the presence of the aforesaid relative movement.

2. The combination defined in claim 1 in which said sensing means includes a light source positioned to direct light through said fluid to be interrupted by said magnetic member when said magnetic member is in said predetermined position, and photoelectric means positioned to receive light from said light source upon movements of said magnetic member away from said predetermined position.

3. The combination defined in claim 2 and which includes a block providing a housing for said magnetic means and for said sensing means, and which includes electric heater means mounted in said block for maintaining said block at a predetermined temperature.

4. The combination defined in claim 3 in which said block has a plurality of incubation wells therein established at said predetermined temperature for storing receptacles of the fluid to be tested and for maintaining said fluids at said predetermined temperature.

5. The combination defined in claim 3 in which said block includes a well adjacent said magnetic means and said sensing means for receiving the aforesaid receptacle means, and said system includes means extending into said well for moving said receptacle means reciprocally past said magnetic means and said sensing means.

6. The combination defined in claim 1 in which said magnetic member is in the form of a steel ball approximating the inner diameter of said receptacle.

7. The combination defined in claim 1 and which includes a timer means for measuring the time required for the viscosity of the fluid sample to exceed said predetennined threshold.

8. The combination defined in claim 7 in which said timer means includes a pulse generator, an impulse counter, and control circuitry for selectively connecting said pulse generator to said impulse counter.

9. The combination defined in claim 8 in which said pulse generator includes a magnetically operated reed switch, magnetic means, and means for cyclically bringing said magnetic means into operative relationship with said reed switch to actuate said switch.

10. The combination defined in claim 9 in which said magnetic means includes a permanent bar magnet, and in which said last-named means includes a turntable supporting said bar magnet adjacent said reed switch and an electric motor for imparting rotational movement to said turntable to bring said bar magnet in and out of operative magnetically coupled relationship with said reed switch.

1 l. In combination for use in apparatus for sensing changes in viscosity of a fluid blood or blood plasma sample, receptacle means containing a fluid thromboplastin or partial thromboplastin reagent, and a magnetic ball positioned in the fluid in the receptacle, said ball having a diameter approximating the inner diameter of said receptacle.

12. The combination defined in claim 11 in which said receptacle comprises a test tube and stopper means sealing said test tube and retaining the aforesaid reagent therein.

13. The combination defined in claim 11 in which said test tube has a bore diameter of the order of 0.199 inch, and said magnetic member is in the form of a ball having a diameter of the order of 0. l 87 inch.

14. The combination defined in claim 11 in which said magnetic member is in the form of a steel ball approximating the inner diameter of said receptacle.

15. A method for detennining the time of reaction by sensing changes in viscosity of a fluid sample undergoing reaction comprising: suspending a magnetic member contained within said fluid sample within a steady state magnetic force field, imparting relative movement between the fluid sample and said magnetic force field, and sensing movement of said magnetic member from a predetermined position within said magnetic force field, said movement being controlled so that the magnetic member does not break the surface of the fluid sample.

16. A method for determining the time of clotting of blood and blood plasma comprising: suspending a magnetic ball contained in a fluid sample of said blood or plasma in admixture with thromboplastin or partial thromboplastin within a steady state magnetic force field, said fluid sample being confined in a transparent tubular container of restricted clearance between the said magnetic ball and the sidewall of the container due to the magnetic ball having a diameter approximating the inner diameter of said test tube, imparting relative movement between the magnetic force field and the fluid sample to cause the magnetic ball to move up and down in said tubular container, adding a solution containing soluble calcium ions to said fluid sample, and measuring the time interval until said magnetic ball is moved from the original position in the magnetic force field by the formation of a clot in said sample, said movement being controlled so that the magnetic ball does not break the surface of the fluid sample.

17. A method for sensing changes in viscosity of a fluid sample which comprises: including a magnetic member in the fluid; creating a magnetic field in the fluid for suspending the magnetic member in a particular position with respect to the magnetic field so long as the viscosity of the fluid is below a predetermined threshold; imparting relative vertical reciprocating movement between said fluid and said magnetic field; and sensing any movement of said magnetic member away from said particular position with respect to said magnetic field, said movement being controlled so that the magnetic member does not break the surface of the fluid sample.

18. The method defined in claim 17 and which includes: directing a light beam through the fluid to be normally interrupted by said magnetic member; and receiving the light beam upon movement of said magnetic member away from said particular position.

19. The method defined in claim 18, and which includes converting the received light beam into electrical energy.

20. The method defined in claim 17 and which includes imparting reciprocal movement to said fluid in a vertical direction.

21. The method defined in claim 17 and which includes timing the interval required for the magnetic member to move away from said particular position.

22. A method for sensing changes in viscosity of a fluid sample which includes providing a magnetic member in the fluid; creating a magnetic field in the fluid for holding the magnetic member in a particular position with respect to the magnetic field so long as the viscosity of the fluid is below a predetermined threshold; imparting reciprocal movement to said fluid in a vertical direction with respect to said magnetic field; directing a light beam through the fluid to be normally interrupted by said magnetic member; receiving the light beam upon movement of said magnetic member away from said particular position; converting the received light beam into electrical energy; and timing the interval required for the magnetic member to move away from said particular position, said movement being controlled so that the magnetic member does not break the surface of the fluid sample.

23. The method defined in claim 17 and which comprises mixing thromboplastin or partial thromboplastin and plasma in the fluid sample.

24. The method defined in claim 17 and which comprises mixing thromboplastin, or partial thromboplastin, plasma and a source of soluble calcium ions in the fluid sample.

25. The method defined in claim 24 in which the thromboplastin or partial thromboplastin, plasma and source of soluble calcium ions are mixed in the sample in substantially equal proportions.

26. The method defined in claim 25 in which the thromboplastin or partial thromboplastin, plasma and source of soluble calcium ions are brought to a test temperature of the order of 37 C.

27. The method defined in claim 25 in which approximately one-tenth of a milliliter each of thromboplastin or partial thromboplastin, plasma and calcium chloride are mixed in substantially equal proportions in the sample.

28. Apparatus for sensing changes in viscosity of a fluid sample including: receptacle means for the fluid; a magnetic member in the fluid in the receptacle means; magnetic means for creating a magnetic field in the receptacle to hold said magnetic member in a predetermined position with respect to said magnetic field so long as the viscosity of said fluid is below a predetermined threshold and in the presence of relative movements between said fluid and said magnetic field; means for sensing movements of said magnetic member away from said predetermined position in the presence of the aforesaid relative movements; a block providing a housing for said magnetic means and for said sensing means and including a well adjacent said magnetic means and said sensing means for receiving said receptacle means; a piston extending vertically into said well from the lower end thereof and reciprocally movable within said well for moving said receptacle means reciprocally past said magnetic means and said sensing means; and a drive mechanism coupled to said piston for imparting vertical reciprocal movement to said piston within said well.

29. The apparatus defined in claim 28 in which said sensing means includes a light source positioned to direct light through said fluid to be interrupted by said magnetic member when said magnetic member is in said predetermined position; and photoelectric means positioned to receive light from said light source upon movements of said magnetic member away from said predetermined position.

30. The apparatus defined in claim 28 and which includes a timer mechanism for measuring the time required for the viscosity in the fluid sample to exceed said predetermined threshold.

31. The apparatus defined in claim 30 and in which the timer mechanism includes a pulse generator having a magnetically operated reed switch; magnetic means; a turntable supporting said magnetic means and positioned relative to said reed switch for cyclically bringing said magnetic means into operative relationship with said reed switch; and an electric motor for imparting rotational movement to said turntable.

32. Apparatus for sensing changes in viscosity of a congealable fluid sample including: a receptacle means for the fluid; a magnetic member suspended in the fluid in the receptacle; magnetic means for creating a magnetic field in the receptacle for holding said magnetic member in a predetermined position with respect to said magnetic field so long as the viscosity of said fluid is below a predetermined threshold and in the presence of relative movements between said fluid and said magnetic field; means coupled to at least one of the aforesaid means for imparting relative vertical reciprocating movement between said receptacle and said magnetic field; and photoelectric means for sensing'movements of aid magnetic member away from said predetermined position in the presence of the aforesaid relative vertical movement.

33. The combination defined in claim 32 and which includes a block providing a housing for said magnetic means and for said photoelectric sensing means and a well adjacent said sensing means for receiving the aforesaid receptacle means, and which includes electric heater means mounted in said block for maintaining said block at a predetermined temperature.

34. The combination defined in claim 33 in which said block has a plurality of incubation wells therein established at said predetermined temperature for storing receptacles of the fluid to be tested and for maintaining said fluids at said predetermined temperature.

35. The combination defined in claim 32 in which said magnetic member is in the form of a steel ball.

36. The combination defined in claim 32 and which includes a timer means for measuring the time required for the viscosity of the fluid sample to exceed said predetermined threshold.

37. The combination defined in claim 36 in which said timer means includes a pulse generator, an impulse counter, and control circuitry for selectively connecting said pulse generator to said impulse counter.

38. The combination defined in claim 37 in which said pulse generator includes a magnetically operated reed switch, magnetic means, and means for cyclically bringing said magnetic means into operative relationship with said reed switch to actuate said switch.

39. The combination defined in claim 38 in which said magnetic means includes a permanent bar magnet, and in which said last-named means includes a turntable supporting said bar magnet adjacent said reed switch and an electric motor for imparting rotational movement to said turntable to bring said bar magnet in and out of operative magnetically coupled relationship with said reed switch.

40. A method for determining the time of reaction by sensing changes in viscosity of a congealable fluid sample undergoing reaction comprising: suspending a magnetic member contained within said fluid sample within a steady state magnetic force field, imparting relative vertical reciprocating movement between the fluid sample and said magnetic force field, and photoelectrically sensing movement of said magnetic member from a predetermined position within said magnetic force field.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2957338 *Nov 29, 1957Oct 25, 1960Great Lakes Carbon CorpViscometer
US3267363 *Apr 18, 1962Aug 16, 1966Becton Dickinson CoElectrical apparatus for fiber detection
US3271112 *Dec 12, 1962Sep 6, 1966Donald L WilliamsApparatus for laboratory testing
US3375705 *Aug 10, 1964Apr 2, 1968Sherwin Williams CoViscosimeter
US3443419 *Oct 18, 1966May 13, 1969American Enka CorpMethod and apparatus for measuring the maturity of viscose
US3520659 *Oct 20, 1967Jul 14, 1970Xerox CorpMethod and apparatus for use in determining prothrombin time of a blood sample
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3775595 *Jun 15, 1972Nov 27, 1973Instrumentation Labor IncApparatus for processing chemical materials held in container structures
US3882716 *Jul 17, 1972May 13, 1975Elliott BeimanCentrifugal apparatus and cell
US3888113 *Oct 3, 1973Jun 10, 1975Baxter Laboratories IncReagent Tube and Stopper Assembly
US3895235 *Mar 18, 1974Jul 15, 1975Illinois Tool WorksLiquid level and specific gravity indicator
US3900290 *Mar 12, 1974Aug 19, 1975Int Octrooi Mij Octropa Nl1973Method and apparatus for determining the degree of platelet aggregation in blood
US3911728 *Feb 7, 1974Oct 14, 1975Daillet S A EtsCoagulation detection apparatus
US3991896 *Nov 27, 1974Nov 16, 1976Baxter Travenol Laboratories, Inc.Stopper assembly
US4116564 *Feb 5, 1976Sep 26, 1978Institut National De La Sante Et De La Recherche Medicale InsermApparatus for the study of plasmas
US4125327 *Nov 1, 1976Nov 14, 1978Gradient Pty. LimitedMethod and apparatus for simultaneously recording reaction times
US4262521 *Aug 27, 1979Apr 21, 1981Sperry CorporationEpoxy resin gel tester
US4320087 *Jan 23, 1978Mar 16, 1982Abbott LaboratoriesImmunoassay or biochemical assay with an adsorber
US4373931 *Oct 3, 1980Feb 15, 1983Olympus Optical Company LimitedMethod of measuring agglutinating reaction and a reaction vessel therefor
US4533519 *Jul 20, 1983Aug 6, 1985Hemotec, Inc.Gas flow coagulation test cartridge having movable member establishing communication between reagent and reaction chambers
US4663127 *Oct 15, 1982May 5, 1987Hemotec, Inc.Gas flow cartridge having resilient flexible membrane with slit separating reaction and reagent chambers
US4679439 *Sep 17, 1985Jul 14, 1987Dorr-Oliver IncorporatedMethod and apparatus for measuring the unsteady sedimentation potential of colloidal particles
US4849340 *Apr 3, 1987Jul 18, 1989Cardiovascular Diagnostics, Inc.Reaction system element and method for performing prothrombin time assay
US4879897 *Aug 18, 1986Nov 14, 1989Commonwealth Scientific And Industrial Research OrganizationMethod and apparatus for the determination of viscosity
US5040410 *Nov 13, 1989Aug 20, 1991The Research Foundation Of State University Of New YorkRheometer
US5174961 *Jan 18, 1991Dec 29, 1992Hemotec, Inc.With separately controlled automatic dispenser subassembly
US5314826 *Aug 23, 1991May 24, 1994Medtronic Hemotec, Inc.Platelet activation and function evaluation technique
US5439650 *Nov 3, 1992Aug 8, 1995Seiko Instruments Inc.Reaction vessel
US5522255 *Aug 31, 1993Jun 4, 1996Boehringer Mannheim CorporationFluid dose, flow and coagulation sensor for medical instrument
US5526111 *Aug 31, 1993Jun 11, 1996Boehringer Mannheim CorporationMethod and apparatus for calculating a coagulation characteristic of a sample of blood a blood fraction or a control
US5629209 *Oct 19, 1995May 13, 1997Braun, Sr.; Walter J.Blood, monitoring position of ferromagnetic disk freely movable in the fluid
US5686659 *Jun 7, 1995Nov 11, 1997Boehringer Mannheim CorporationFluid dose flow and coagulation sensor for medical instrument
US5710622 *Jun 7, 1995Jan 20, 1998Boehringer Mannheim CorporationFluid dose, flow and coagulation sensor for medical instrument
US5731212 *Dec 20, 1994Mar 24, 1998International Technidyne CorporationAccuracy
US5789664 *Mar 29, 1996Aug 4, 1998Boehringer Mannheim CorporationFor determining a characteristic of a biological fluid or a control
US5841023 *Aug 31, 1993Nov 24, 1998Boehringer Mannheim CorporationFor monitoring a change in a characteristic of a biological fluid
US5925319 *Apr 30, 1996Jul 20, 1999Medtronic, Inc.Test cartridge for evaluating blood platelet functionality
US6134394 *Jul 15, 1999Oct 17, 2000Ricoh Company, Ltd.Image forming apparatus for detecting viscosity of a liquid type developer by utilizing a developer density detecting device
US6189370Jun 17, 1998Feb 20, 2001Roche Diagnostics CorporationFluid dose, flow and coagulation sensor for medical instrument
US6245569Feb 26, 1998Jun 12, 2001Dade Behring Marburg GmbhUsing stepwise threshold-value method; the kinetics of reaction are evaluated by measuring the change in a variable which depends on the reaction and measuring the time taken for a limit value to be exceeded; coagulation
US6534778 *Jul 17, 2000Mar 18, 2003Yamatake CorporationApparatus for detecting balls carried in tube
US6575017Nov 28, 2000Jun 10, 2003Roche Diagnostics Corporation, Inc.Fluid dose, flow and coagulation sensor for medical instrument
US6955920Jun 11, 1999Oct 18, 2005Medtronic, Inc.comprises 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine/collagen as clotting agent; for use during heart and cardiopulmonary surgery
US7092085Jan 20, 2004Aug 15, 2006Desa Richard JSample holder with intense magnetic field
US7117721Feb 4, 2003Oct 10, 2006Roche Diagnostics Operations, Inc.Fluid dose, flow and coagulation sensor for medical instrument
US7699966May 11, 2005Apr 20, 2010Medtronic, Inc.Point of care heparin determination system
US7955818 *Feb 23, 2005Jun 7, 2011Thierry BernardiMethod for detecting the formation of biofilms
US8338129Mar 8, 2007Dec 25, 2012Biofilm ControlMethod for reading images, in particular for studying the development of biofilm in a culture medium
US8801918Mar 29, 2010Aug 12, 2014Medtronic, Inc.Point of care heparin determination system
DE3127560A1 *Jul 11, 1981Feb 17, 1983Jochimsen SiegfriedDevice for detecting and measuring the blood coagulating time by means of a metal block, which can be temperature-controlled and serves to accommodate the measuring cuvette, a stirring device and a light-optical (photooptical) turbidity measuring device
DE4113330A1 *Apr 24, 1991Oct 29, 1992Amelung Gmbh HeinrichVorrichtung zur photometrischen bestimmung des gerinnungsverhaltens von blut, blutplasma oder dergleichen
DE19542225A1 *Nov 1, 1995May 7, 1997Buero Fuer Biomedizinische IngVerfahren und Vorrichtung zur Bestimmung von rheologischen und mechanischen Stoffkenngrößen
DE19542225B4 *Nov 1, 1995May 26, 2011L.U.M. GmbhVerfahren und Vorrichtung zur Bestimmung von rheologischen und mechanischen Stoffkenngrößen
EP0046589A1 *Aug 22, 1981Mar 3, 1982Ernst ThöneApparatus for determining the viscosity of a liquid
EP0090192A1 *Mar 3, 1983Oct 5, 1983Holger BehnkApparatus for taking and measuring the coagulation time of blood by a pulse generated by changing the position of a steel ball in a test tube containing the reagent
EP0861687A1 *Jan 27, 1998Sep 2, 1998Dade Behring Marburg GmbHMethod to evaluate reaction courses
EP2233923A1Feb 18, 2010Sep 29, 2010Commissariat à l'Énergie Atomique et aux Énergies AlternativesMethod and apparatus for the characterisation of the coagulation dynamics or sedimentation of blood or blood serum
WO1995006869A1 *Aug 18, 1994Mar 9, 1995Boehringer Mannheim CorpMagnetic system for medical instrument
WO2005090944A1 *Feb 23, 2005Sep 29, 2005Bara NicolasMethod and device for detecting the formation and development of biofilms in a culture medium
WO2007104881A2 *Mar 8, 2007Sep 20, 2007Biofilm ControlMethod for reading images, in particular for studying the development of biofilm in a culture medium
WO2008089604A1 *Feb 26, 2007Jul 31, 2008Gang LiA device for measuring liquid coagulation time
WO2012001312A1Jun 30, 2011Jan 5, 2012Biofilm ControlMethod for detecting molecular interactions
Classifications
U.S. Classification436/69, 335/205, 73/54.19, 422/73, 250/573, 356/39, 250/222.2, 206/220, 73/54.15, 356/72
International ClassificationG01N11/10, G01N33/49
Cooperative ClassificationG01N33/4905, G01N11/10
European ClassificationG01N33/49B, G01N11/10
Legal Events
DateCodeEventDescription
Jul 14, 1988ASAssignment
Owner name: TECHNICON INSTRUMENTS CORPORATION, 511 BENEDICT AV
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:COOPER LABORATORIES, INC.,;REEL/FRAME:004926/0396
Effective date: 19880628
Nov 2, 1982ASAssignment
Owner name: COOPER LABORATORES, INC., 3145 PORTER DRIVE, PALO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:BAXTER TRAVENOL LABORATORIES, INC., A CORP. OF DE;REEL/FRAME:004067/0785
Effective date: 19820917