Abstract:
A method and apparatus are provided for measuring hemostasis. The apparatus includes a torque sensing column having a torque sensing element and a drive ring disposed around a body of the column and in registration with the column so as to allow rotation of the drive ring around a longitudinal axis of the column. The apparatus further includes a first guide shaft rigidly secured to the drive ring, the guide shaft extending parallel to the longitudinal axis of the column and a cup holder movably attached to the guide shaft, allowing the cup holder to move parallel to the longitudinal axis of the column. The apparatus also includes a sample cup adapted to engage the cup holder on a outer surface and the torque sensing element of the torque sensing column on an inner surface.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is a Continuation of U.S. application Ser. No. 09/255,099, filed Feb. 22, 1999, by Cohen et al., now U.S. Pat. No. 6,225,126, issued May 1, 2001. 
    
    
     FIELD OF THE INVENTION 
     The field of the invention relates to testing of blood samples and more particularly to devices for testing hemostasis. 
     BACKGROUND OF THE INVENTION 
     Methods of measuring the coagulation characteristics of blood are known. Some such devices attempt to simulate the natural flow of blood in the veins and arteries of a living subject. 
     An accurate measurement of the ability of a patient&#39;s blood to coagulate in a timely and effective fashion is crucial to certain surgical and medical procedures. Accelerated (rapid) and accurate detection of abnormal coagulations is also of particular importance with respect to appropriate treatment to be given to patients suffering from clotting disorders. Often the condition of such patients makes it necessary to administer anti-coagulants, certain fibrinolytic agents, anti-platelet agents, or blood components in a quantity which may only be determined after taking into account the abnormal components or “factors” of the patient&#39;s blood which may be contributing to the clotting disorder. 
     One measure of blood clotting is provided by the Thromelastograph (TEG®) Coagulation Analyzer manufactured by Haemoscope of Skokie, Ill. The Haemoscope device measures the mechanical properties of the clot throughout its structural development. 
     A number of references describe instruments for measuring blood clotting characteristics based upon simple mechanical movements. These instruments monitor the elastic properties of blood as it is induced to clot under a low shear environment resembling sluggish venous blood flow. The patterns of change in shear elasticity enable the determination of the kinetics of clot formation, as well as the strength and stability of the formed clot. The strength and stability of the clot provide information about the ability of the clot to perform the “work of hemostasis” (i.e., stop or prevent abnormal bleeding) and about the adequacy of blood platelet-fibrin interaction. The kinetics of clot formation provide information about coagulation factors available for clot formation. Analysis of the information provides results which are useful to predict bleeding, to monitor and manage thrombosis, and to monitor fibrinolysis. 
     While the instrument of the reference is effective in measuring hemostasis based upon resistance to mechanical movement, the apparatus necessary to cause movement and torque measurement is unnecessarily complex. The apparatus is even more difficult to load and unload. Because of the importance of measuring blood clotting, a better apparatus for measuring hemostasis is needed. 
     SUMMARY 
     A method and apparatus are provided for measuring hemostasis. In one embodiment, the apparatus includes a torque sensing column having a torque sensing element and a drive ring disposed around a body of the column and in registration with the column so as to allow rotation of the drive ring around a longitudinal axis of the column. The embodiment further includes a first guide shaft rigidly secured to the drive ring, the guide shaft extending parallel to the longitudinal axis of the column and a cup holder movably attached to the guide shaft, allowing the cup holder to move parallel to the longitudinal axis of the column. The embodiment also includes a sample cup assembly adapted to engage the cup holder on an outer surface and the torque sensing element of the torque sensing column on an inner surface. 
     The apparatus includes novel features which allow for the quick and easy replacement of blood samples. A unobstructed front surface of the apparatus allows the operator better access for easier cup and blood sample placement. A control lever on a torque measuring column of the apparatus allows a pin of the sample cup assembly to be quickly and easily ejected. The sample cup holder may be lifted to a convenient position and a button on the bottom of the holder activated to release the sample cup assembly for easy removal. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 depicts an embodiment of a system for measuring hemostasis in accordance with the invention; 
     FIG. 2 depicts an embodiment of a measuring unit for use with the system of FIG. 1; 
     FIG. 3 depicts an embodiment of a torque measuring column for use with the measuring unit of FIG. 2; 
     FIG. 4 depicts an example of a sample cup carrier for use with the measuring unit of FIG. 2; 
     FIG. 5 depicts a cut-away side view of the cup carrier of FIG. 4; 
     FIG. 6 depicts an example of a drive mechanism of the measuring unit of FIG. 2; 
     FIG. 7 depicts a side view of a mounting feature of a torque measuring column of the system of FIG. 1; 
     FIG. 8 depicts an alignment fixture that may be used with the system of FIG. 1; and 
     FIG. 9 depicts a top view of a torque measuring pin of the system of FIG.  1 . 
    
    
     DETAILED DESCRIPTION 
     FIG. 1 is a block diagram of a system  10  for measuring hemostasis, generally, in accordance with an illustrated embodiment of the invention. Included within the system  10  is a measuring unit  12  and data collection unit  14  (e.g., a personal computer (PC), datalogger, etc.). The system  10  is constructed in a modular form. Features discussed below provide for the quick and easy replacement of individual modules of the system  10  without the need for re-calibration or complex re-alignment steps. 
     Under the illustrated embodiment, hemostasis may be measured by the system  10  in terms of a series of shear elasticity measurements (e.g., in terms of dyn/cm 2 ). The resulting hemostasis profile may be used as a measure of the time it takes for the first fibrin strand to be formed, the kinetics of clot formation, the strength of the clot (in shear elasticity units of dyn/cm 2 ) and dissolution of the clot. 
     In general, the system  10  measures a clot&#39;s physical properties by the use of a combination cylindrical cup and matching shear-inducing pin. The combination cup and matching pin may be constructed generally as taught by U.S. Pat. No. 5,223,227 to Zuckerman, assigned to the assignee of the present invention and incorporated herein by reference. 
     FIG. 2 is a perspective view of one example of the measuring unit  12 . Included within the measuring unit  12  may be a first and a second measuring station  14 ,  16 . While the system  10  shows two stations,  14 ,  16 , it should be understood that there is no practical limit of the number of test stations that may be incorporated into the system  10 . The measuring stations  14 ,  16  may be functionally identical and facilitate the processing of two separate blood samples at the same time. 
     An explanation will now be provided of the operation of the first measuring station  14 . For purposes of explanation, it may be assumed that the structure of the second station  16  is substantially identical to first station  14 . 
     Each measuring station  14 ,  16  may include at least three main structures. The stations  14 ,  16  may include a cup carrier  18 , a cup carrier drive system  20  and a torque measuring column  22 . 
     The cup carrier  18  may be provided with a receptacle sized to accept a sample cup  24  (containing a blood sample). Once a sample cup  24  is inserted into the cup carrier  18 , a pin  26  may be inserted into the cup  24  of the cup carrier  18 . The sample cup  24  and pin  26  may be fabricated of an inexpensive material (e.g., plastic) intended for a one-time use. 
     One difference between the cup and matching pin of the Zuckerman &#39;227 patent over that used herein relates to a corfiguration of the pin. Under the embodiment, the torque sensing pin  26  (FIG. 9) is provided with a fully enclosing upper flange  114  which functions to completely close an upper opening of the sample cup  24 . Such closure has been found important in preserving the integrity of the blood sample against the effects of drying and oxidation. 
     The pin  26  is also provided with a circular aperture  116 . The circular aperture reduces the difficulty in engaging the pin  26  with the torque measuring column  22  as explained in more detail below. 
     Once the sample cup  24  and pin  26  is inserted into the cup carrier  18 , the carrier  18  may be manually lifted into contact with a bottom of the torque measuring column  22 . Once the carrier  18  makes contact with the bottom of the measuring column  22 , a skewer  28  (see cross-sectional view of the column  22  in FIG. 3) engages the circular center hole of the pin  26 . 
     FIG. 4 is a cut-away view of an embodiment of the cup carrier  18 . Shown included within the cup carrier  18  is a sample cup  24  and pin  26 . Shown between the cup  24  and pin  26  is a blood sample  30 . 
     The cup  24  may be fabricated for any convenient size blood sample (e.g., 360 μL) consistent with sampling accuracy. An outer diameter of the pin  26  and inner diameter of the cup  24  may be selected to provide a 1 mm gap on each side (2 mm total) within which the blood sample resides. 
     During testing, the cup holder  18  is oscillated (i.e., rotated) around the longitudinal axis of the skewer  28 . For example, the cup holder  18  may be rotated to a distance of 2.4 degrees on either side of a center point during each cycle (4.83 degrees of total travel) Each cycle may last  10  seconds with a 1½ second rest period at each end of the excursion. 
     During rotation of the cup holder  18  and cup  24 , the relative movement of the cup  24  and stationary position of the pin  26  creates a shear action between the inner surface of the cup  24  and outer surface of the pin  26 . The shearing action causes a shear movement among adjacent blood molecules lying between, resulting in coagulation. 
     As the blood coagulates, the shear resistance between adjacent molecules in the blood sample increases and the shear force that may be transmitted from the cup  24  to the pin  26  increases. By measuring the torque imparted to the skewer  28  through the blood  30 , a thrombo-elastic graph may be created over a time period. 
     In order to preserve the integrity of the blood testing process, a port  93  (FIG. 3) is provided through the torque measuring column  22  for introducing a protective oil over the blood sample  30 . The port  93  is angled for the insertion of a pipette into the junction area between the pin  26  and cup  24 . 
     By introducing the oil into the area of the junction, capillary action causes the oil to be drawn into the cup  24  and overlay and protect the blood  30 . Protection of the blood  30  has been found to be an important feature (against drying of the blood) where extended periods are required for coagulation testing. 
     As a further feature for protection of the blood sample  30 , a relatively closed cavity  38  is provided at the lower end of each torque measuring column  22 . The closed cavity functions to provide a protected environment for the blood sample during testing. Such closed cavity  38  not only reduces the possibility that airborne contaminants may enter the sample  30 , but also tends to control humidity of the environment surrounding the cup  24 . 
     Returning now to the illustrative example of FIG. 3, it may be seen that the skewer  28  is coupled to a torque transmission shaft  32  which freely floats within the column  22  during test conditions, suspended from a tungsten wire  34 . The tungsten wire  34  provides a progressive resistance to torque from the skewer  28 . 
     The tungsten wire, in turn, is supported by a stationary cross-bar  31  disposed in a V-groove. The V-groove provides a vertical reference point for alignment of the pin  26  and cup  24 . 
     An appropriate non-contacting rotation detector (e.g., rotary variable differential transformer (RVTD), rotary variable inductive transformer (RVIT), laser/mirror/CCD arrangement, etc.)  36  may be provided to detect rotation of the transmission shaft  32  (and skewer  28 ) caused by torque transmitted by the shear force through the blood to the pin  26 . By multiplying a detected rotation of the shaft by a spring constant of the tungsten wire  34 , a torque value may be periodically determined and transmitted to the data collection unit  14  through the interconnecting cable  16 . 
     The tungsten wire  34  may be fabricated to any appropriate diameter (e.g., 0.007 inch) and length (e.g., 2 inches) consistent with an expected torque measuring range. Further, the column  22  is fabricated for easy replacement of the wire  34  (or the column  22  itself) where it becomes necessary (for research or other purposes) to adjust a torque measuring range. This also greatly simplifies replacement of torsion wires damaged by misuse or otherwise. 
     The simplified procedure for replacing the torsion wire greatly increases the flexibility and utility of the system  10 . For example, the easily replaceable torsion wire allows a weaker torsion wire (for increased sensitivity) to be used for measuring weaker clots, or a stronger torsion wire for stronger clots. 
     To replace a wire  34 , the user moves the control lever  42  to a locked position. Next, the set screw  35  (FIG. 3) is loosened to release the wire  34 . 
     To remove the wire  34 , a screw-on cap  33  is removed and a pair of needle-nose pliers (not shown) may be used to grasp an end  31  of the wire  34  and lift it out of the column  22 . A replacement wire  34  may be inserted in place of the removed wire  34 . 
     Once the replacement wire  34  is inserted, the set screw  35  may again be tightened. Once the set screw is tightened, the skewer  28  may be centered using centering screws  102 ,  104  (FIG.  1 ). Adjustment of the centering screws  102 ,  104  allows a support cap  106  (FIG. 3) to be laterally adjusted to center the skewer  28  over the cup  24 . 
     To center the skewer  28  a fixture  110  (FIG. 8) may be inserted in place of the cup  24  into the cup holder  18 . A spacer block (not shown) may be used to bring the skewer  28  into vertical proximity with a reference point  112  of the fixture  110 . The centering screws  102 ,  104  may be adjusted as necessary to center the skewer  28  over the reference point  112  of the fixture  110 . 
     To complete installation of the new wire  34 , a torque constant (i.e., measured in torque units per degree of deflection) may be entered through the keyboard  15  into the CPU  14 . Alternatively, a lookup table of torque constants may be provided within the CPU  14  and accessed via a part number of a wire  34  entered through the keyboard. The torque value may be used to determine a measured torque by multiplying a torque deflection (in degrees) by the torque constant. 
     Turning now to loading of the cup carrier  18 , a side cut-away view is shown in FIG. 5 of the cup carrier  18 . A cavity  50  is provided in an upper surface of the cup carrier  18  to receive the sample cup  24 . Once the cup  24  and tip  26  are placed in the cavity  50 , the cup carrier is lifted into contact with the bottom of the column  22  of FIG.  3 . Once in contact a spring-loaded button  52  provided on the bottom of the cup carrier  18  is activated to seat the tip  26  onto the skewer  28 . As the button  52  is activated, an inner hole of the tip  26  is urged onto the skewer  28  up over a shoulder  40  on the skewer  28  within a cavity  38  located in the bottom of the column  22 . 
     Once the tip  26  is seated on the skewer  28 , the cup carrier  18  may be lowered and the cup  24  seated back into its own respective cavity  50 . After the cup  24  is seated, the cup  24  may be filled with a blood sample  30  and again raised into an operating position against the bottom of the column  22 . The cup  24  may be raised and lowered slightly several times, thereby using the pin  26  to mix the sample prior to testing. 
     Once the carrier  18  has been seated against the column  22 , a registration lever  42  (FIG. 2) may be rotated to the right along a slot  86  to a test position. Moving the lever  42  to a test position brings the tip  26  into a proper position with respect to the cup  24 . Rotating the lever  42  to the right rotates a cam  44  which lowers the torque transmission shaft  32  from a locked position by a sufficient distance (e.g., 0.035 inch) to bring the tip  26  and cup into a proper spatial alignment with the cup  24 . 
     Once the cup  24  and tip  26  are brought into a proper relationship, an operator (not shown) may enter a patient name through a keyboard  15  on the data recorder  14 . At the same time the drive mechanism  20  may be activated and testing may begin. 
     A detached partial perspective view of an illustrative embodiment of the drive system  20  is shown in FIG.  6 . While the partial view of FIG. 6 shows the drive system  20  for the right testing station  16 , it may be assumed that the drive system for the left testing station  14  would be substantially identical (with the exception of the cam follower  68  facing the other direction). 
     Included within the drive system is a drive ring  60 . A pair of parallel guide shafts  62 ,  64  extend downwardly from the drive ring  60 . A positioning rod  66  extends radially outwardly from the drive ring  60  and engages a geared drive motor  72  through a cam follower  68  and cam  70 . 
     The drive ring  60  circumferentially engages the column  22  around a first abutting surface  46  (FIG.  3 ). The column  22  maintains the drive ring  60  in a radial alignment with the column  22  by moveable registration of an inner surface of the drive ring  60  against the first abutting surface  46 . 
     Longitudinal alignment of the drive ring  60  with the column  22  is maintained by trapping the drive ring  60  between a second abutting surface  48  (FIG. 3) and a mating surface  74  on a top plate  76  of the measuring unit  12 . The column  22  is retained in a fixed relationship with the top plate  76  through the use of a stepped hole  81  (FIG.  7 ). An outer diameter  49  (FIG. 3) of the column  22  is sized to engage the hole  81  of a slightly larger diameter  79  (e.g., 0.005-0.010 inch) A step  77  at the bottom of the hole  81  allows for a fixed spacing between the second abutting surface  48  and top plate  76  and free rotation of the drive ring  60 . 
     A set of three screws  78  may be used to secure the column  22  to the top plate  76 . Removal of the screws  78  also allows for the simple replacement of the torque measuring column  22  should the need arise. 
     The set of guide shafts  62 ,  64  extend downwardly from the guide ring  60  through a set of slots  80  in the top plate  76  to engage the cup carrier  18 . A set of linear bearings  82  on each carrier  18  allow the carrier  18  to be easily moved up or down the guide shafts  62 ,  64 . A set of spring loaded clips  19  (FIG. 4) are provided below each linear bearing  82  to maintain the carrier  19  in a selected position during testing and otherwise. 
     Movement of the guide ring  60  is accomplished by operation of the positioning rod  66 . The cam follower  68  of the positioning rod  66  is maintained in contact with the cam  70  by operation of a spring  84 . More specifically, a clockwise motion of the ring  60  (when viewed from above) is caused by the cam. A counterclockwise motion of the ring  60  is caused by the spring  84 . 
     To obtain an appropriate cycling rate, the motor  72  may be geared to obtain a speed of one revolution every 10 seconds. A flat spot may be provided on the cam  70  at a high point and low point to allow for a one and one-half second pause at the end of each direction of travel. The profile of the cam  70  may be changed as needed to provide a wide range of periodic motions. 
     The CPU  14  may provide for any number of test intervals. For example, a standard test interval of 10-15 minutes may be used. Alternatively, the test may be extended to 2-3 hours for research purposes. 
     To maintain the blood sample  30  at an optimal temperature (e.g., 98.6° F. +/−0.1° F.) for testing, a heater  54  and temperature sensor  55  (e.g., RTD, thermocouple, etc.) (FIG. 5) are provided within each carrier  18 . The temperature sensors  55  are disposed directly against the receptacle holding the cup  24 . A flexible cable  56  may be used to connect and control the heater  54  through operation of a temperature controller  86  located within the sampling unit  12 . 
     A dual channel temperature controller (e.g., a Love Controls Model 32A022-9502) may be used to provide separate temperature control and set points for each carrier  18 . The use of separate temperature sensors  55  and close proximity to the blood sample  30  ensures that each blood sample  30  is maintained at a precisely controlled temperature. The availability of separate set points on the controller  86  for each carrier provides the versatility of performing standard testing or testing under abnormal conditions. 
     Once a cup  24  and pin  26  have been installed into the system  10  (as described above), a blood sample  30  may be directed into the cup  24  using a pipette (not shown). The cup  24  may be raised and lowered against the pin  26  to mix the blood. The hemostasis profile may be obtained as described above. 
     Once testing is complete, the sample cup assembly  24 ,  26  may be easily removed by a series of quickly executed steps. The tip  26  may be ejected from the skewer  28  by moving the lever  42  to a load position (as shown in FIG.  2 ). The lever  42  may then be simply moved downward into a second slot  88  to eject the tip  26 . Moving the lever  42  downward causes a center ring  94  to move downward based upon its distance from a pivot point  91 . As the center ring  94  moves down it presses against a collar  92 , which acts against a spring  96  to eject the tip  26 . 
     Once the tip  26  has been ejected, the carrier  18  may be moved to a lower position and the cup  24  and tip  26  removed. The cup  24  and tip  26  may be ejected from the carrier  18  by lowering the carrier  18  until the button  52  on the bottom of the carrier  18  makes contact with a lower cover  97 . 
     With a first hand, an operator may eject the pin  26 . At the same time, the operator may begin moving the cup carrier  18  downward with her other hand. As the carrier  18  is moved downward, the cover  97  activates the button  52 , lifting the cup assembly. As the button  52  is activated, the operator may remove the cup assembly and replace it with another cup assembly. The sequence of steps may be performed as part of a single rapid sequence of steps without fear of spilling or compromising the integrity of the testing procedure. 
     Once the cup  24  and tip  26  have been removed, the carrier  18  may also be removed for cleaning and sterilization. To accomplish removal, the cover  97  is first removed. Under the cover  97 , a cavity  98  is provided below the ends of the guide shafts  62 ,  64 . The cavities  98  allow the carrier  18  to be easily slid off the ends of the guide shafts  62 ,  64 . Once detached from the guide shafts  62 ,  64 , the carrier  18  may be slid forward and out of the measuring unit  12 . 
     The simple and rugged construction of the test unit  12  allows for reliable and accurate testing of blood samples. The easy removal and disposal of sample cups and tips reduces the possibility of contamination or infection by users. The easy removal and cleaning of related parts further improves upon the overall ease of use of the measuring unit. 
     Specific embodiments of a method and apparatus for measuring hemostasis according to the present invention have been described for the purpose of illustrating the manner in which the invention is made and used. It should be understood that the implementation of other variations and modifications of the invention and its various aspects will be apparent to one skilled in the art, and that the invention is not limited by the specific embodiments described. Therefore, it is contemplated to cover the present invention and any and all modifications, variations, or equivalents that fall within the true spirit and scope of the basic underlying principles disclosed and claimed herein.