Abstract:
A method and apparatus for testing the efficacy of agents (e.g., new drugs, old drugs, biologically-active agents, etc.) by removing a predetermined amount of blood from a living being and placing this predetermined amount of blood in continuous motion in a temperature-controlled environment and then removing samples from the continuously-moving predetermined amount of blood. The drug, or drugs, or agents under test can then be administered to the removed samples, instead of into the living being, thereby avoiding subjecting the living being to any risk of any adverse reaction while utilizing blood samples that simulate the circulating blood of the living being.

Description:
FIELD OF THE INVENTION  
         [0001]    The invention pertains to methods and apparatus for testing the efficacy of agents on blood, and more particularly, to methods and apparatus for simulating blood flow using a sample of blood, outside of the body, while administering agents thereto and monitoring the effects of such agents on the blood sample.  
         BACKGROUND OF INVENTION  
         [0002]    The testing of agents (e.g., drugs, biologically-active agents, etc.) to determine the their effects (e.g., toxic levels, therapeutic levels, etc.) on the blood of a living being (e.g., reducing the viscosity of the blood) usually involves administering small amounts of the agent to a living being, e.g., a human patient, and then observing the patient&#39;s vital signs and any other biological or molecular reaction. It is important, especially with regard to determining the effects of the agent on a living being&#39;s blood viscosity, to have the agent administered into the circulating blood of the living being rather than having the agent administered into a static sample of blood removed from the patient and then observing any changes in the blood sample.  
           [0003]    However, such a procedure not only may subject a patient to risk of a severe reaction, but it is tedious in preparing the patient and is inconvenient to the patient who must remain under observation and/or restricted behavior until the study is complete.  
           [0004]    Thus, there remains a need for an apparatus and method for testing the efficacy of an agent on the circulating blood of a living being while avoiding the risk of the living being suffering a severe reaction to the drug, as well as the inconvenience to the living being.  
         SUMMARY OF THE INVENTION  
         [0005]    A method for testing the efficacy of an agent (e.g., a drug, biologically-active agents, etc.) on the circulating blood of a living being (e.g., a human being). The method comprises the steps of: (a) removing a predetermined amount of blood (e.g., 50-100 cc) from the living being into a collector (e.g., an intravenous bag that is uncoated or coated with a biocompatible coating); (b) placing the collector containing the predetermined amount of blood in continuous motion such that the predetermined amount of blood is continuously moving within the collector; (c) maintaining the temperature of the collector containing the predetermined amount of blood at the temperature of the body of the living being while such blood is in the continuous motion; and (d) removing a portion (e.g, 10 cc) of the predetermined amount of blood for administering the agent thereto and immediately analyzing the effect of the agent on the portion of the predetermined amount of blood.  
           [0006]    An apparatus for storing blood of a living being (e.g., a human being) outside of the body of the living being while simulating the movement and temperature of the circulating blood. The apparatus comprises: a collector (e.g., an intravenous bag) adapted for receiving a predetermined amount of blood (50-100 cc) from the living being and whereby the collector comprises an internal biocompatible coating (e.g., phosphoryl choline); a motion device (e.g, a swivel rocker, a reciprocating arcuate motion generator, a reciprocating linear motion generator, etc.) upon, or in, which is positioned the collector and whereby the motion device provides continuous motion to the collector; a temperature-controlled unit (e.g., an incubator) in which is positioned the collector and motion device and whereby the temperature-controlled unit maintains the collector at the body temperature of the living being.  
       
    
    
     DESCRIPTION OF THE DRAWINGS  
       [0007]    [0007]FIG. 1 is an isometric view, in partial view, of the in vivo blood storage system;  
         [0008]    [0008]FIG. 2 is a side elevational view, partially in section, of the present invention using an alternative motion device;  
         [0009]    [0009]FIG. 3 is a side elevational view, partially in section, of the present invention using another motion device;  
         [0010]    [0010]FIG. 4 is a functional diagram of a dual riser/single capillary tube viscometer in accordance with application Ser. No. 09/573,267; and  
         [0011]    [0011]FIG. 5 is a functional diagram of a mass detection capillary viscometer in accordance with application Ser. No. 09/789,350. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0012]    Referring now in detail to the various figures of the drawing wherein like reference characters refer to like parts, there is shown at  120  in FIG. 1, an in-vivo blood storage system. The system  120  basically comprises a motion device  122 , a collector  124  (e.g., an intravenous, IV, bag) disposed on or in the motion device  122  and, both of which, are positioned in a temperature-controlled unit  126  (e.g., an incubator). Although not shown, the interior of the collector  124  comprises a biocompatible coating (e.g., an anti-thrombogenic material, such as Heparin, and/or anti-thrombolytic coatings, e.g. phosphoryl choline, etc., available from Biocompatibles, Ltd., Uxbridge, UK) to replicate the interior of the blood vessel tissue. The motion device  122  operates continuously to effect the high and low shear rates that are experienced by the circulating blood as it travels through the living being&#39;s blood vessels. The temperature-controlled unit  126  operates to maintain the temperature of the blood in the collector  124  at the temperature of the living being&#39;s body.  
         [0013]    In use, the empty collector  124  is positioned on or in the motion device  122  which is energized to provide the continuous movement; in addition, the temperature-controlled unit  126  is also energized to generate the body temperature of the living being. With the motion device  122  and temperature-controlled unit  126  operating and at the proper temperature, a predetermined amount of blood  121  (e.g., 50-100 cc) is diverted into the collector  124  via a lumen (e.g., a catheter/needle inserted into blood vessel of the living being), not shown; the lumen is coupled to the collector  124  via a self-sealing surface  125  (e.g., those used in serum containers into which a needle is pushed). Once the collector  124  is filled with the predetermined amount of blood  121 , the lumen is disengaged from the living being and the collector  124 . At this point, there is now a continuously-moving portion of the living being&#39;s blood that is available for testing.  
         [0014]    An example of such testing may comprise the following. It may be desirable to determine the efficacy of a certain new drug, or agent, on changing the viscosity of the living being&#39;s blood. To that end, the clinician removes a sample of blood (e.g., 10 cc), not shown, from the collector  124  via the self-sealing surface  125  and then administers the new drug or agent. This mixture is then immediately deposited into a blood viscometer that moves the mixture through a plurality of shear rates; such viscometers are disclosed in application Ser. No. 091573,267entitled DUAL RISER/SINGLE CAPILLARY and application Ser. No. 09/789,350 entitled MASS DETECTION CAPILLARY VISCOMETER, both of which are assigned to the same Assignee as the present invention, namely Rheologics, Inc. (formerly Visco Technologies, Inc.), and both of whose entire disclosures are incorporated by reference herein. Other suitable viscosity measuring apparatus may be used in lieu of these apparatus. In particular, FIG. 3 depicts a viscometer  20  disclosed in application Ser. No. 09/573,267. The mixture is deposited into the upper end  128  of one of a riser tube R 1  of the viscometer  20 . In accordance with the operation of the viscometer  20 , a failing column  82  of the mixture is generated in the riser tube R 1  while a rising column of the mixture  84  is generated in a second riser tube R 2 . This movement is analyzed by the viscometer  20  in accordance with application Ser. No. 09/573,267 and the viscosity of the mixture determined. This is compared to the viscosity of the blood before the drug or agent is administered.  
         [0015]    Alternatively, as shown in FIG. 4, the mixture can be deposited into the open end  228  of the riser tube R of the viscometer  20 ′. In accordance with the operation of the viscometer  20 ′, a falling column of the mixture is generated in the riser tube R and the increasing mass of the collected mixture detected by the mass detector. This increasing mass is analyzed by the viscometer  20 ′ in accordance with application Ser. No. 09/789,350 and the viscosity of the mixture determined. This is compared to the viscosity of the blood before the drug or agent is administered.  
         [0016]    As shown in FIG. 1, the motion device  122  may comprise a rocker device using three-dimensional motion. For example, the motion device  122  may comprise the Cole Parmer® Rocker with Three-Dimensional Motion, part number EW-51702-05. In accordance with such operation, each corner of the support plate  127  is serially moved into a downward position, thereby causing the three-dimensional motion.  
         [0017]    Alternatively, as shown in FIG. 2, the motion device  122  may comprise the device  122 ′ that generates a reciprocating arcuate motion  129 . For example, a motor  131  drives one end of a clevis  133  having another end attached to an intermediate point on a support member  135 . At the top of the support member  135  is a collector support surface  137 . As the motor  131  rotates, the collector  124  is subjected to the reciprocating arcuate motion  129 .  
         [0018]    Furthermore, as shown in FIG. 3, the motion device  122  may comprise a linear motion device  122 ″ that generates reciprocating linear motion  149 . For example, a motor  141  drives one end of a clevis  143  having another end attached to one end of a collector support surface  145 . As the motor  141  rotates, the collector  124  is subjected to the reciprocating linear motion  149 .  
         [0019]    The incubator  126  may comprise the Cole Parmer® EW-39401-05 High-Performance Incubator. The enclosure of the incubator  126  may also provide a darkened environment which is similar to the blood vessels through which the circulating blood normally flows.  
         [0020]    It should be understood that although one agent or drug is mentioned as being administered to the sample removed from the collector  124 , it is within the broadest scope of the present invention to include a plurality of agents or drugs being administered to the sample.  
         [0021]    It should also be understood that the analysis that the sample removed from the collector  124  is subjected to is not limited to viscosity determination. Rather, the sample can be analyzed for an entire battery of tests or screening. Whatever test/screening is conducted, that test/screening is immediately conducted once the sample is removed from the collector  124 .  
         [0022]    It should be noted that, if desired, an adulterant may be added to the interior of the collector to ensure that the blood remains fluid and does not clot to any extent which would prevent a viable measurement of its viscosity.  
         [0023]    Moreover, the subject invention isn&#39;t limited to the particular mechanisms for keeping the blood in motion, as discussed above. Thus any suitable means for keeping the blood from stasis are contemplated by this invention, e.g., pulsatile pumps, rotary pumps, mechanical mixers, agitators, etc.  
         [0024]    Without further elaboration, the foregoing will so fully illustrate our invention that others may, by applying current or future knowledge, readily adopt the same for use under various conditions of service.