US3704099A

US3704099A - Coagulometer

Info

Publication number: US3704099A
Application number: US20341A
Authority: US
Inventors: Manuel Claude Sanz
Original assignee: Micromedic Systems Inc
Current assignee: ICN Micromedic Systems Inc; Rohm and Haas Co
Priority date: 1969-03-19
Filing date: 1970-03-17
Publication date: 1972-11-28
Anticipated expiration: 1989-11-28
Also published as: DE2014133A1; AU1283570A; IL34114A0; NL7003916A; IL34113A0; ZA701872B; ES377637A1; DE2014123A1; GB1310246A; GB1310245A; US3692487A; FR2039643A5; CH506791A; FR2039644A5; NL7003917A; CH533307A

Abstract

AN APPARATUS FOR DETERMINING THE COAGULATION TIME OF BLOOD AND OTHER LIQUIDS WHICH HAS A MOTOR DRIVEN ROTATING STIRRER THAT IS MOUNTED FOR VERTICAL MOVEMENT ON A BASE BELOW WHICH IS MOUNTED A ROTATABLE INDEXING SUPPORT MEMBER BEARING LIQUID SAMPLES. A MANUALLY OPERABLE RACK IS USED TO INSERT THE STIRRER IN T HE C ONTAINERS AND TO START THE MOTOR TO ROTATE THE STIRRER. A SLIP SWITCH IS USED TO BREAK THE CIRCUIT WHEN THE STIRRER ENCOUNTERS RESISTANCE CAUSED BY THE COAGULATION. THE TIME FOR COAGULATION IS READ DIRECTLY OFF A COUNTER ATTACHED TO THE MOTOR.

Description

NOV. 28 c SANZ I COAGULOMETER Filed March 17-. 1970 v 4 Sheets-Sheet 1 FIG. I

4 Sheets-Shed 2 M. C. SANZ COAGULOMETER Nov. 28, 1972 Filed March 17, 1970 M. c. SANZ COAGULOMETER Nov. 28, 1972 4 Sheets-Sheet Filed March 17, 1970 M. C. SANZ COAGULOMETER Nov. 28, 1972 4 Sheets-Sheet 4 Filed March 17, 1970 will? United States Patent 3,704,099 COAGULOMETER Manuel Claude Sanz, Geneva, Switzerland, assignor to Micromedic Systems, Inc., Philadelphia, Pa. Filed Mar. 17, 1970, Ser. No. 20,341 Claims priority, application Switzerland, Mar. 19, 1969, 4,124/ 69 Int. Cl. G01n 11/14, 33/16, 33/26 U.S. Cl. 23253 R 11 Claims ABSTRACT OF THE DISCLOSURE This invention provides apparatus for measuring the coagulation time of a blood sample.

The coagulation of human blood is the result of a particularly complex process of a biochemical nature which calls into play a dozen components called factors, conventionally denoted by means of Roman numerals I, II, III, etc.

The absence or deficiency of one or more of these factors causes, in the human body, the coagulation of the blood to deteriorate or even to become impossible in certain cases and almost always causes more or less acute ailments in certain parts of the body, in particular the liver, as well as certain defects in the metabolism.

The detection of the factors which may be deficient or absent in blood is clearly very important, whether it be for the purpose of deciding the most appropriate treatment for eliminating or circumscribing certain ailments that may have been observed in a subject, or, as a precautionary measure, before any surgical operation, for avoiding, for example, haemorrhages.

This detection is also of particular importance in respect of the treatment to be given to patients suifering from a thrombosis and to whom it is necessary to administer anticoagulants in a quantity which must clearly be determined after taking into account the abnormal factors which were the cause of the thrombosis.

Among the numerous tests which are performed to carry out this detection, that proposed by A. Quick is one of the simplest and swiftest to make. This test which is essentially intended to show up any concentration deficiency of the factors I, II, V, VII and X of the blood, is broadly speaking carried out in the following manner: after adding a solution of anticoagulant (solution of trisodium citrate or sodium oxalate) to freshly drawn blood, thereby removing from the blood the Ca++ ions (factor IV) and preventing coagulation thereof, the mixture is subjected to a centrifugal operation and the plasma which comes to float is drawn off. To this floating plasma is then added an equal quantity of a suspension of thromboplastine (a tissue extract of a kind corresponding to that of factor III of the blood) and the mixture is brought 3,704,099 Patented Nov. 28, 1972 to a temperature of 37 C. Into this mixture is then introduced a solution of calcium chloride (to add Ca++ ions), also brought to 37 C., and the coagulation time of the resulting composite liquid is measured.

According to one variant of this test, proposed by Soulier, it is possible to replace the floating plasma by natural freshly drawn blood.

If the concentration of the factors I, II, V, VII and X of the tested blood is normal, the coagulation time is of the order of 10 to 15 seconds, according to the activity of the thromboplastine used. On the other hand, a coagulation time greater than the 'value obtained with normal blood indicates a deficiency of one or more factors without, however, indicating which one; other kinds of tests enable these factors to be identified.

The measurement of this coagulation time, originally eifected by means of a simple chronometer which an operator stopped in an empiric manner, on the basis of a visual estimation of the state of coagulation reached by the composite liquid under examination, has for sometime been carried out automatically by means of various forms of apparatus.

In U.S. patent specification No. $053,078 there is disclosed an apparatus consisting of a viscometer which comprises a rotating feeler that dips into the composite liquid to be tested, this liquid being contained in a device that is rotated at constant speed. With this feeler is associated an electric switch for controlling the electric supply of the motor that drives the container and of a time counter. This switch is adapted to open under the action of the feeler when the viscosity of the liquid being tested reaches a predetermined value, corresponding to a particular state of coagulation of the blood or of the plasma, depending on the nature of the composite liquid being tested, the feeler being then moved angularly forward by the thickening liquid to an extent sufficient to actuate the switch. The reading which is then given by the time counter corresponds to the coagulation time of the blood or of the plasma being tested.

In the published specification of Dutch patent application No. 68/ 14,790 there is disclosed another form of apparatus for measuring blood coagulation time. This form of apparatus involves the use of a container device having three compartments of which the first contains a calcium salt and the second contains thromboplastine, these two compartments being subsequently made to communicate with the third compartment, this latter compartment being intended to receive the blood to be tested and containing a stirrer consisting of a magnetisable rod. This particular apparatus is also a viscometer and comprises a support for the container device, a rotary magnet, a magnetisable armature extending from the magnet to near the third compartment of the container device mounted on the support for driving the magnetisable stirring rod inside this compartment, a pick-off coil surrounding the armature and connected to the terminals of an electronic device for detecting flux variations in the coil, these variations being caused, during operation, by changes in the position of the stirring rod in relation to the armature under the action of the increasing viscosity of the liquid in which the stirring rod is required to move, this increasing viscosity being due to the coagulating blood.

In the specification of our co-pending patent application No. 20,340 filed Mar. 17, 1970, we have described a container device for carrying out a blood coagulation test which includes two superposed enclosures that are separated from one another by a removable partition, the first enclosure being intended to receive a blood sample and containing a suspension of at least one of the blood coagulation factors in a solution of anticoagulant whereas the other enclosure contains a calcium salt solution, and which further includes a stirrer defining a wall portion which lies opposite the partition and which forms part of the upper enclosure, said wall portion being de tachable from the remainder of the upper enclosure and the stirrer having a substantially upstanding actuating rod projecting above the upper enclosure.

As described in the specification of this co-pending patent application, the device, to become operative, involves introducing a metered quantity of blood into the first enclosure, heating the contents of both enclosures to 37 C., exerting on the stirrer rod sufficient pressure to introduce the stirrer first into the first enclosure and then into the second upon removal of the partition, rotating the stirrer thereby in particular homogeneously to mix the liquid contents of the two enclosures, and determining the amount of time that elapses between the moment when the two enclosures are made to communicats with one another and the moment when the resistive torque acting on the stirrer, due to the viscosity of the composite liquid in the device, reaches a predetermined value that corresponds to a particular state of coagulation of the blood contained in this liquid.

An object of the invention is to provide an apparatus for automatically measuring the coagulation time of a blood sample in a container device of the kind set forth, with reference to our co-pending patent application.

The apparatus proyided by the present invention comprises a rotary assembly mounted for rotation about a vertical axis, an electric motor for rotatably driving said assembly, means for measuring the duration of the rotary driving action of the motor, a switch associated and rotatable with said rotary assembly for controlling the supply of electric current to the measuring means and to the motor, a support for a sample-containing device located beneath the rotary assembly in a position such that the longitudinal axis of the stirrer rod of said samplecontaining device when placed on the support may lie in axial alignment with the rotational axis of said rotary assembly, a pin associated with said rotary assembly coaxially with the rotational axis thereof, said pin being mounted for pivotal movement about said axis, means for releasably coupling the lower end of the pin to said stirrer rod, a pin-positioning finger rigid with said pin, first and second abutments arranged to cooperate with said finger to define a first extreme angular position for the pin in relation to the rotary assembly and a second extreme angular position for the pin situated past the first position in relation to the direction in which the drive motor rotates said assembly, a member for actuating said switch which is kinematically rigid with said pin and which is adapted to close said switch when the pin is in its firstextreme angular position, and a member for holding the pin in said first extreme angular position for as long as any resistive torque on the pin opposing rotation of said assembly remains below a certain value; wherein said pin is axially slidable in relation to the rotary assembly; wherein said assembly includes a tubular member of insulating material coaxial with the rotational axis of the assembly and surrounding said pin over part of its length, said tubular member having a longitudinal slot formed in the wall thereof into which extends said pinpositioning finger and of which the edges that define the upper and lower ends thereof respectively provide third and fourth abutments arranged to cooperate with said finger to define a first extreme axial position for the pin in which said pin lies remote from any sample-containing device on said support and a second extreme axial position for the pin in which said pin, after coming into engagement with the stirred rod of a sample-containing device on said support through said coupling means and after removal of said partition and of said wall portion, holds said stirrer depressed in the enclosures of said de vice; wherein one longitudinal edge of said slot extends vertically over its entire length and forms, along the lower portion thereof, said first abutment, and the other longitudinal edge of the slot includes a first portion extending vertically from the top edge of the slot to provide the pin-positioning finger in cooperation with the corresponding portion of said one longitudinal edge with a rectilinear path of travel over the major part of its displacement between said third and fourth abutments thereby to hold said pin in its first extreme angular position over a corresponding length of its axial displacement between said extreme axial positions, and a second portion which is offset in relation to the first towards the bottom edge of the slot and which forms therealong said second abutment; wherein said switch-actuating member is formed by said pin-positioning finger; wherein said switch includes a resilient contact blade which normally occupies an inoperative, rest, position corresponding to the open position of the switch and which is adapted to be flexed into an operative position corresponding to the closed position of the switch, said blade having an engageable part which projects inwardly into said slot, when said blade is in its inoperative position, in a portion of the slot corresponding to the location occupied by said pin-positioning finger when the latter bears both against said one longitudinal edge and said bottom edge of the slot, and to a depth sufiicient to enable said resilient blade to be flexed by said finger into said operative position upon said finger being moved to said location; and wherein it further comprises a push-member, kinematical- 1y rigid with said pin, for slidably moving said pin between said first and second extreme axial position.

In the accompanying diagrammatic drawings:

FIG. 1 is a side elevation of one form of embodiment of the apparatus provided by the invention;

FIG. 2 is a plan view of the apparatus shown in FIG. 1 without its cover;

FIG. 3 is a section through the apparatus shown in FIGS. 1 and 2, along line III-III of FIG. 2;

FIG. 4 is'a section through a detail of the apparatus shown in FIGS. 1 to 3, on a larger scale, along the line IVIV of FIG. 2;

FIG. 5 is a view similar to that of FIG. 4 but showing certain components in different relative positions;

FIG. 6 is a cross-section along line VI-VI of FIG. 4;

FIG. 7 represents the detail of FIG. 4 viewed in the direction of arrow A, some of the components being shown in elevation and others being shown in section;

FIG. 8 is a diagram of the electrical circuitry in the apparatus shown in FIGS. 1 to 2; and

FIGS. 9, l0 and 11 illustrate three stages in the operation of the apparatus shown in FIGS. 1 to 3 in conjunction with a sample-containing device.

' The illustrated apparatus is more particularly intended to carry out the last two stages of a coagulometric test on a blood sample, these stages being (a) the mixing of the blood with coagulation reactants and (b) the detection of a particular state of coagulation of the blood and themeasurernent of the time taken by the blood being tested to reach this state from the moment stage (a) has been carried out.

For this, the blood and the reactants that are required for its coagulation are placed in container devices of the kind described in the specification of our above identified co-pending patent application and of which one can be seen in axial section in FIGS. 9, 10 and 11.

As can in particular be seen from FIG. 9 and as described in detail in the specification of our above mentioned application, these devices comprise each two tubular elements 1 and 2, made for instance of polyethylene 0r polypropylene, that are interengageably assembled together and within which are provided three transverse partitions. The first of these partitions is formed by the lower end of a rod 3, coaxially arranged inside element 1, and by a tearable annular membrane which connects the edge of the lower end of rod 3 to the inner surface of element 1; the second partition is formed by a circular disc of which the edge is connected to the inner surface of element 2 by a tearable annular membrane also; and the third partition is formed by a disc 5 which is forcefitted into the opening of element 2 some distance up the latter.

These three partitions define within the assembled elements 1 and 2 a first enclosure E that extends into both elements, and a second enclosure E in element 2 only.

Enclosure E which is meant to receive the blood sample to be tested, contains a suspension of a blood coagulation factor in a solution of a blood anticoagulant. This may consist of a suspension of thromboplastine in a solution of trisodium citrate or of sodium oxalate.

Enclosure E contains a solution of a calcium salt, e.g. calcium chloride, which is chemically equivalent to the anticoagulant solution contained in enclosure E Also, the amount of solution in enclosure E is the same as the amount of liquid in enclosure E It should be noted that the space occupied by the liquid in enclosure E is equal to at most half the total space in enclosure E, as the latter is also intended to receive a quantity of blood to be tested equal to that of the above liquid.

As indicated in the specification of our aforementioned application, the above container device is supplied ready for use, i.e. with enclosure E and E already each containing their appropriate liquids.

Once the blood sample to be tested has been collected, the container device is rapidly moved in an axial direction and abruptly stopped so as to bring all of the liquid contained in enclosure E into the portion thereof in element 1; the tubular elements 1 and 2 are then taken apart and a metered quantity of the blood to be tested is introduced into the other portion of enclosure E i.e. that in element 2, and the two elements are then reassembled again. Since the Ca++ ions are fixed by the trisodium citrate or the sodium oxalate, depending on the anticoagulant that is used for the suspension of coagulation factor in enclosure E the blood will not coagulate. Once this operation has been completed, use is made of the apparatus illustrated in FIGS. 1 to 3.

This apparatus comprises a casing formed by a rectangular base of plastic material which rests on a support, not shown, by means of pillars 11 and along the right hand edge of which is secured a vertical wall 12, also rectangular and of plastic material, carrying a switch 13 to control the supply of electricity to the apparatus; the casing further comprises a cover 14 secured along the three free edges of the base 10 and of the wall 12 by means of screws not shown.

On the base 10 is mounted a synchronous motor M with which is associated reduction gearing D having an output shaft d connected to a horizontal shaft 15 by a resilient sleeve 16. This shaft 15 is rotatably mounted in two

flanges

17a and 17b of a frame 17 for a counter 18 secured to the base 10 and having a set of numberbearing drums 19 which are driven off a toothed wheel 20, rigid with the shaft 15, and through the intermediary of a pinion 21 which controls the rotation of the first drum 19, the following drums of the set being each driven by the preceding drum, in the usual manner.

As the counter 18 is directly coupled to the shaft 15 and therefore to the motor M through the reduction gearing D, and as this motor is a synchronous motor rotating at practically constant speed, it is possible to determine the length of time the motor M has rotated by reading the number indicated by the counter 18 at the end of such rotation, provided of course that the counter 18 has been set to zero before the motor M begins to rotate. If the first drum 19, starting from the left hand side (FIGS.

1 and 2) is numbered from 0 to 9, the second drum is numbered 0 to 5, the third 0 to 9 and the fourth 0 to 9 also, the meter 18 can give an indication corresponding to at most 9 minutes, 59 seconds and 9 tenths of a second. The counter 18 can therefore be used to indicate coagulation time in the case of the Quick test, since this time is normally of the order of 10 to 15 seconds.

In order to set the counter 18 to zero, the pinion 21 must be rotated in a direction opposite to the normal direction of rotation under the action of the toothed wheel 20. For this purpose, the shaft carrying the pinion 21 passes through the flange 17b of frame 17 and carries at its free end a pinion 22 which engages firstly, with a rack 23a rigid with a vertical rod 23 and secondly, with a wheel 24. This wheel is rotatably mounted on an upstanding lug 24a rigid with the base 10 and meshes with an endless screw 25 carried by one end of a shaft 26 (FIG. 3).

The rod 23 has a length greater than the height of the casing of the apparatus and is mounted for vertical sliding movement in two apertures, one being provided in the base 10 and the other being provided in the top of the cover 14 directly above the aperture in the base 10.

Above the rack 23a the rod 23 carries a horizontal arm 27 and, at its upper end, a knob 28 by means of which the rod can be held and actuated axially between a first, lower, position as shown in FIG. 5 and a second, upper, position in which the arm 27 comes close to the cover 14. The amplitude of this displacement is sufficient to set the counter 18 to zero, this setting to zero operation being effected when the rod 23 is moved from its upper position to its lower position.

At its free end opposite the coupling sleeve 16, the shaft 15 carries a bevel gear 29 meshing with another bevel gear 30. Bevel gear 30 is mounted on a cylindrical root 31a of a tubular member 31 (FIGS. 1 and 4) which is rotatably fitted into a circular aperture 10a formed in the base 10. At the upper end of its central passage, member 31 carries a metal bush 32 rotatably fitted into a circular aperture 33'a provided in a metal bridge piece 33' fixed to the wall 12 of the casing this aperture 33a being located directly above the aperture 10a in base 10.

Spring washers

34a and 34b assist in maintaining the tubular member 31 in a predetermined axial position.

As shown in detail in FIG. 7, member 31 is formed in its wall with a longitudinally extending slot 35 having relatively close parallel edges at its upper part 35a, the width of the lower part 3512 being about three times that of the upper part 35a.

In front of this slot 35, member 31 carries a resilient metal blade 36 which is secured to this member a screw 36:: and which contacts bush 32 via this screw. The blade 36 is thus connected electrically to the bridge piece 33' via the bush 32 and the spring washer 34b.

As can be seen from FIGS. 4 and 5, the blade 36 is formed with a bent part 36b near its lower end, this bent part projecting into the slot =35 of member 31 when blade 36 is at rest. Moreover, the lower end portion of blade 36 is engaged in an annular recess 29a formed in the top side of a gear 29. When the blade 36 is in its rest position as shown in FIG. 5 it occupies a radially innermost position, out of contact with gear 29, and when the blade 36 is flexed radially outwardly, away from its rest position, it comes into contact with gear '29, this outward flexing movement of blade 36 being brought about by a pushmember 37 which projects through the slot 35 and comes to bear against the bent part 36b of the blade as shown in FIG. 4.

As the gear 29 is electrically connected to the bridge piece 33 by the spring washer 3 4b, it will be appreciated that when the resilient blade 36 is moved into the flexed position shown in FIG. 4, the

bridge piece

33' and 33" are connected together electrically whereas they are cut tion of rest in FIG. 5.

Blade 36 and the inner surface of the recess 29a: in gear 29 thus act as the movable contact and as the stationary contact of an electric current switch which is identified by a reference I in the FIG. 8 circuit diagram and which is placed between one terminal of the synchronous motor M for driving the apparatus and one pole of the switch 13 for controlling the supply of electric current to the apparatus.

In this connection, it will be observed from FIGS. 2 and '8 that the bridge piece 33' is linked by a connection p firstly to the motor M and secondly to one side of a compensating capacitor C. As for the bridge piece 33" it is linked by a connection q to the movable contact of switch 13.

Motor M and the other side of capacitor C are linked by a connection In to one of the lines, V, of a single phase a.c. supply, whereas the stationary contact of switch 13 is linked by a connection 11 to the other line, 0, of the supply.

As can be seen from FIGS. 4 and 5 of the accompanying drawings, the push-member 37, made of plastic material, is mounted on a pin 38 which extends axially through the tubular member 31 and which is slidably mounted in the root portion 31a thereof and in a bush 39 of plastic material which is mounted with a tight fit in the metal bush 32. Besides this axial movement, the pin 38 can also perform a slight angular movement, the extent of this movement being limited by the engagement of the pushmember 37 with either of the longitudinal edges of slot 35 along the wider part 35a thereof. The two extreme angular positions that the push-member 37 can occupy in this part 35a of slot 35 can be seen from FIG. 6, these two positions determining the extent to which pin 38 can turn. In the first of these positions, push-member 37 is drawn in full lines whereas in the second position pushrnember 37 is drawn in chain-dotted lines and is identifie as 37'.

Pin 38 can be moved to either of two extreme axial positions in relation to the tubular member 31, i.e. a first, uppermost, position, not shown, in which the pushmember 37 comes to bear against the top edge of slot 35 and a second, lowermost, position, shown in FIGS. 4 and 7, in Which the push-member 37 comes to bear against the bottom edge of slot 35. It is to be noted that it is only when the pin 38 occupies simultaneously both this second extreme axial position and its first extreme angular position that the tip of push-member 37 can engage the most inwardly projecting portion of the bent part 36b of blade 36, and that it is only under these conditions that the tip of blade 36 will come into contact with gear 39. Furthermore, since the edges along the wider part 35a of slot 35 are spaced apart by a distance slightly greater than the width of push-member 37 it will be appreciated that not only will the push-member slide freely between these edges, for instance when the pin 38 is being: moved from its uppermost position to its lowermost position, but also that this sliding movement will take place with the pin 38 being kept in its first extreme angular position.

Moreover, during sliding movement, the push-member 37 normally remains out of engagement with the blade 36 over the major part of its travel between the top and bottom edges of slot 35 and the push-member 3-7 only comes into contact with the blade 36 when it reaches the.

immediate vicinity of the bent part 36b of the latter so that the switch I can only be closed when the blade 36 and the push-member 37 occupy the relative positions visible in FIG. 4 (corresponding to the lowermost position of pin 38).

When the switch I is closed, the pin 38 can only be moved out of its first angular position to its second angular position by exerting on pin 38 a torque having a direction w (FIG. 6), the intensity of the torque being directly dependent on the elastic force exerted by the flexed blade 36 on the push-member 37 and on the amount of frictional resistance therebetween. As will be explained later,

this elastic force is carefully chosen in dependence on the coagulometric test which the illustrated apparatus is required to perform.

To enable the pin 38 to be moved from its first extreme axial position to its second extreme axial position, or vice versa, pin 38 carries at its top end a disc 40 (FIG. 1) engaging in a slot 27a made in the arm 27 that is secured to the rod 23, thus rendering pin 38 kinematically rigid with rod 23.

The lower end of this pin is shaped to form a lancet 38a and carries a cap 41, the opening of which has a crosssection slightly greater than that of the rod 3 of a container device of the kind visible in FIGS. 9 to 11. The lancet 38a is in fact intended to be driven into the upper end of said rod, as will be indicated below, the cap serving to cover this end so as to provide lateral guidance of the rod during the driving in operation of the lancet into the rod.

The right hand end of the shaft 26 (FIG. 3) carries a bevel pinion 42 meshing with a wheel 43 rotatably mounted on a vertical shaft 44. On this shaft 44 is secured an arm 45 carrying a pivotal pawl 46 which is held by a spring 47 in permanent contact with the teeth of a wheel 48. A second pawl 49, which is subjected to the action of a spring 49a, prevents any rotation of the wheel 48 in an anticlockwise direction (BIG. 2).

The wheel 48 is keyed on the upper end of a hollow shaft 50 rotatably mounted in a bearing 51 fitted into an aperture 10b formed in the base 10 and secured to the latter.

At its lower end, the shaft 50 carries a metal plate 52, for example of aluminium, from the upper face of which project ten equidistantly spaced cylindrical bosses 52a. Each of these bosses has a diameter and a height respectively corresponding to the diameter and depth of the recess provided in the lower portion of element 2 of a container device, between the disc 5 and the free end of this element (FIG. 9).

In the plate 52 is arranged an annular electrical resistor R (FIGS. 3 and 8) which is suitably insulated in relation to plate 52 and which serves to heat this plate in order to maintain it at a temperature of 37 C. The supply of this resistor is effected by electrical conductors 53 extending through the shaft 50 and by four contact rings 55 of which the lowermost two are connected to said conductors and which are carried by a sleeve 54 of insulating material which is secured to the upper end of this shaft.

In one of the bosses 52a is also mounted a thermocouple T which is connected to a switching box 58 (FIGS. 2 and 8) by means of two conductors 57 which also extend through the hollow shaft 50 and which lead to the two uppermost rings 55 of sleeve 54 (FIG. 3). A pair of sliding contacts 59 connect the rings that are associated with the thermocouple T to the switching box 58. In a similar manner, a second pair of sliding contacts 60 connect the rings to which are connected the conductors 53 for the resistor R, one to this same switching box, and the other, via connections r and m, to the line V of the electrical supply for the apparatus. The switching box 58 is moreover connected to the switch 13 via a connection 2 (FIGS. 2 and 8). This switching box 58 is arranged in such a way as to control the supply of current to the resistor R so long as the thermocouple T indicates that the plate 52 has a temperature lower than 37 (3., whereby the devices that contain the blood to be tested and the reactants (thromboplastine and CaCl and that are placed on this plate will be kept at this temperature throughout the test.

Before fully describing the operation of the described apparatus, it should further be noted that:

(a) The location of the hollow shaft 50 and the dimensions of the plate 52 are such that, when this plate rotates, the various container devices carried thereby successively come to lie in alignment with the pin 38, below the latter;

(b) The number of teeth on the wheel 48 is equal to the number of bosses 52a on plate 52;

(c) When the rod 23 is in its lowermost position, as in FIG. 3, the pawl 47 is in a retracted position, shown by chain-dotted lines in FIG. 2, this pawl moving to the position shown in full lines, having regard to the various gear reductions which take place, only when the rod 23 has been lifted into a position corresponding to the first extreme axial position (i.e. the uppermost position) of the pin 38; in this connection, the plate 52- can only be driven in the direction F (FIG. 2) as it is prevented from moving in the opposite direction by the pawl 49; the pawl 46 thus jumps over the teeth of the wheel 48 when it is returned to the position shown in chain-dotted lines;

(cl) The length of the pin 38 is such that, in its first extreme axial position (i.e. the uppermost position), the lancet 38a of pin 38 lies above the level of the top edges of the container devices carried by plate 52, thereby enabling the latter to be rotated in direction F In order to use the described apparatus, the rod 23 is first raised thus opening the switch I (FIG. 8), the pushmember 37 being moved above the bent part 36b of blade 36 and the latter moving to its inoperative, rest, position, away from the gear 29 (FIG. the switch 13 is then closed so as to feed current to the resistor R in plate 52 and to heat this plate to 37 C. On the plate 52 are then arranged ten container devices, each one containing, as described, firstly a metered quantity of a mixture of blood and of thromboplastine suspension in trisodium citrate solution, and secondly a metered quantity of sodium chloride solution, these metered quantities having all previously been heated to a temperature of 37 C., for instance by placing these devices in an atmosphere having that temperature.

At this point, the counter 18 reads zero and the motor M is at a stop. The rod 23 is then moved to its lowermost position, shown in FIGS. 1 and 3. As the pin 38 is kinematically rigid with the rod 23, and as its cap extends slightly above one of the container devices carried by the plate 52, the action of moving the rod 23, in the manner indicated, first causes the lancet 38a of pin 38 to be driven into the upper end of the rod 3 of the container device lying therebeneath (-FIG. 9). Then, as the downward movement of the rod 23- continues, the pin 38 exerts on the rod 3 of this container device an axial thrust in direction F (FIG. 9), which, if it is sufliciently strong, causes the weak annular membrane that connects the rod 3 to the tubular element 1 of the device, to break, thus causing the stirring end of the rod 3 to be pushed into enclosure E Once through enclosure E rod 3 engages disc 4 (FIG. 10) and transmits to the latter a force which, if strong enough, causes the annular membrane 2d that connects disc 4 to the tubular element 2 to break also so that the stirring end of rod 3 also pentrates into the enclosure E of the container device, which enclosure contains the solution of calcium chloride.

When the rod 23 reaches its lowermost position (FIGS. 1 and 3), the pin. 38 and the rod 3 which is fixed to pin 38 occupy the position seen in FIG. 11, in which position the push-member 3-7, that is rigid with pin 38, presses the blade 36 against the gear wheel 29', thereby closing the switch I. The motor M then begins to rotate to drive with synchronous speed the counter 18, the tubular member 31, the pin 38 and hence also the rod 3 that is secured to the lower end of the pin 38.

But from the moment when the calcium chloride solution has been able to mix with the mixture of trisodium citrate solution, thromboplastine and blood, i.e. from the moment when the partition constituted by the disc 4 has yielded, the liquid mixture in the container device begins to coagulate, becomes more and more viscous and tends to oppose to a greater and greater extent the rotary movement imparted to the rod 3 and therefore the rotation of the pin 38. At a certain instant, the braking action that is exerted by the coagulated mixture becomes greater than the holding action of blade 36 on push-member 37. As a result pin 38 is pivoted into its second extreme angular position and the push-member 37 comes to occupy the disengagement position 37' visible in FIG. 6; the blade 36 then ceases to be in contact with the gear wheel 29 and the motor M stops, as also the counter 18.

The numerical indication given by the drums 1-9 of the counter 18 is indicative of the number of revolutions which the motor M has performed since the beginning of this particular operation and hence of the time this operation has taken, since the motor M is a synchronous motor having a substantially constant rotational speed.

It is thus by reading this numerical indication that it becomes possible to deduce, in each case, whether the tested samples of blood have normal coagulation factors or not.

When a counter reading is finished, the rod 23 and its associated pin 38 are raised, thereby enabling the pin 38 to be released from the rod 3 of the container device that has hardlybeen used for the coagulometry test, the said rod being held back in the container device by the coagulated mass filling enclosures E and E thereof.

By virtue of this upward movement of the rod 23, the plate 52 is also caused to rotate through an angle such as to bring below the pin 38 the second of the ten container devices which this plate carries. It should be pointed out at this juncture that the angular displacement of plate 52 does not take place throughout upward vertical movement of the rod 23, but only after the latter has effected about 40% of its travel. It is indeed essential for the pin 38 to be almost out of the container device which has just been used to carry out the test so that the device should not strike the pin when the plate 52 begins its angular movement. This time lag in the actuation of the plate is achieved by giving the pawl 47 a path of travel greater than the length of the pitch of the teeth on the wheel 48 but less than double this pitch. This path of travel may be about 1.8 times the pitch if the locking pawl 49 is in contact with the radial flank of a tooth when the pawl 46 is in the position shown in full lines, i.e. at the end of its path of travel during the driving phase thereof. In its second, inoperative, position shown in chaindotted lines in FIG. 2 (retracted position of the pawl), the pawl 46 will be distant from the radial flank of the tooth, against which it will subsequently be required to bear, by a length substantially equal to 0.8 times the pitch of the teeth. It will thus be appreciated that, in order to drive the wheel 48 and hence the plate 52 in direction F the pawl must first travel a non-activating distance, while remaining in contact with the edge of the tooth preceding that it is required to push. It is during this time when the pawl 45 does not drive the plate 52, that the pin 38 moves out of the container device which has just been used for the performance of a test.

It is to be noted that in carrying out blood coagulation tests other than the Quick or Soulier test, the thromboplastine solution may be replaced by a solution of at least one other coagulant factor. Thus, in order to carry out a Stypven test, for showing up abnormality of the factors II, V and X only, and especially the last of these factors, the thromboplastine suspension is replaced by a solution containing for example viper venom. In such a case, the coagulation time is of the order of 13 to 14 seconds.

I claim:

1. An apparatus for measuring the coagulation time of blood samples contained in capsules, said apparatus comprising a housing, drive means within said housing, an elongated shaft mounted for rotation within said housing and extending through a portion of said housing and depending therefrom, a non-conducting tubing means surrounding and engaging that portion of said shaft contained within said housing and adapted to rotate therewith, said drive means operatively connected to said tubing means to rotate said tubing and said shaft, circuit means associated with said drive means and said tubing means, and a cam means slidably connected to that portion of said shaft contained within said housing normally keeping said circuit means closed to provide power to said drive means and said cam means adapted to break said circuit upon said shaft encountering a predetermined resistanee caused by said sample beginning to coagulate and slipping relative to said tubing means, a counter connected between drive means and said shaft means and adapted to count the number of rotations of said shaft means and means adapted to raise said shaft and reset said counter simultaneously.

2. An apparatus as in claim 1 wherein the depending Y end of said shaft is tapered to form a lancet, said lancet adapted to engage a stirrer in a capsule containing a blood sample.

3. An apparatus as in claim 2 wherein said lancet has a cap positioned thereon, said cap opening downward and adapted to surround the top of a stirrer which is engaged by said lancet.

4. An apparatus as in claim 1 including a longitudinal slot in said tubing having a widened arcuate portion at its lower end, said cam means comprising a member fixed on said shaft and protruding through said slot, a resilient electrical contact means adjacent said slot and said cam means normally biasing said contact means to complete said circuit means.

5. An apparatus for determining the viscosity of liquid samples contained in containers comprising a base, a motor, a counter connected to said motor to count the number of revolutions thereof, indicia on said counter translating the number of revolutions of said motor into time units, vertically slidable means on said base and operatively connected to said counter to reset the same, said motor operatively connected to a rotatable tubular member and adapted to rotate the same, a shaft journalled for longitudinal movement within said tubular member and depending below said base for engaging a stirrer located within a sample container, said shaft and said vertically slidable means being operatively connected to enable the shaft to be raised and lowered, circuit means connected to said motor, and a switch means located on the upper portion of said shaft and adapted to break said circuit when the stirring shaft encounters resistance and slips rotatively relative to said tubular member as a result of said sample coagulating upon stirring and said shaft having a lancet means at its lower end for engaging a stirrer in a container containing a blood sample.

6. An apparatus as in claim 5 including means for supporting a plurality of sample containers beneath said stirring shaft, gear means and pawl means connecting said vertically slidable means with said container supporting means to advance said means upon upward movement of said vertically slidable means.

7. An apparatus as in claim 6 wherein said container supporting means comprises a rotatable support member, depending shaft means mounting said support member to said base, a second gear means on said shaft means cooperating with said pawl means to rotate said support member when said vertically slidable member and said shaft are raised so as to position the next sample container under said shaft to allow said lancet to engage a stirrer in said container.

8. An apparatus as in claim 6 wherein said vertically slidable member is a rack and said counter has a pinion gear attached thereto engaging said rack.

9. An apparatus as in claim 6 including heating means located in said container supporting means for maintaining said containers at a predetermined temperature.

10. An apparatus as in claim 6 wherein said switch means includes a vertical slot in said tubular member terminating in a widened portion at the bottom and a cam member fixed to said shaft and projecting from said slot, a resilient contact means adjacent said slot and adapted to be biased by said cam means when said cam means is at the bottom of the slot to close said circuit means when said shaft and tubular member are rotating at the same speed whereby said contact starts said motor when the shaft is lowered to engage a stirrer in a container and stops said motor when the speed of the shaft slows upon coagulation of said sample in relation to said tubular member thus allowing the cam to move arcuately within said widened slot portion to disengage said contact.

11. An apparatus as in claim 10 wherein said motor is operatively connected to said tubular member by a bevel gear and said resilient contact means is a spring secured to said tubular member and adapted to be biased into engagement with said bevel gear to close said circuit.

References Cited UNITED STATES PATENTS 3,520,659 7/1970 Steinberg et al. 23253 X 3,267,364 8/1966 Page et al. 23230 BX 3,162,038 12/1964 Roberson et al. 73-59 3,440,866 4/1969 Ness et al. 7364.1 2,423,687 7/1947 Davis et al. 73-59 X JOSEPH SCOVRONEK, Primary Examiner U.S. Cl. X.R.