Patent Publication Number: US-2021190758-A1

Title: Blood coagulometer and method

Description:
STATEMENT OF RELATED APPLICATIONS 
     This application depends from and claims priority to PCT/US2017/017030 entitled Blood Coagulometer and Method filed on Feb. 8, 2017, which depends from and claims priority to U.S. Provisional Application No. 62/293,120 filed on Feb. 9, 2016. 
    
    
     FIELD OF THE INVENTION 
     This application relates to an apparatus and a method of testing a blood sample. More specifically, this application relates to an apparatus and a method for determining the clotting capacity of a sample of blood obtained from a patient. This application further relates to an apparatus and a method for determining the capacity of a clotting blood sample to adhere to a contacted structure, and for reliably diagnosing certain blood conditions. 
     BACKGROUND OF THE INVENTION 
     The process of blood coagulation (thrombogenesis) results in blood clotting and involves a coagulation cascade affected by factors including enzymes which cleave downstream proteins. The maintenance of proper clotting balance is critical. Disorders effecting coagulation of a patient&#39;s blood can lead to uncontrolled bleeding (hemorrhage) or uncontrolled clotting (thrombosis) that can prevent blood flow to critical organs such as, for example, the heart or the brain. Coagulation may be altered for therapeutic purposes, for example when cardiac stent patients are treated with aspirin. 
     Tests are available for evaluating the function of the clotting system in the blood of mammals. Commonly used tests confirm functioning of various parts of the enzyme cleavage process, such as prothrombin time (PT) and partial thromboplastin time. An alternative method of testing the clotting system is thromboelastography (“TEG”), described by Trapani, L., in “Thromboelastography: Current Applications, Future Directions,”  Open Journal of Anesthesiology , January 2013. TEG methods include the rotation of a blood sample in a cuvette about a thin wire wetted portion, or probe, to measure clot formation, clot strength and other parameters. The resistance to rotation of the cuvette about the probe is measured to detect blood clot formation. 
     In addition to the clotting enzyme cascade, which produces fibrin, coagulation is affected by platelet function. Platelet functions include signal transduction, surface adhesion and clot contraction. It is necessary for the blood clot to adhere to surface of the vessel wall in order to slow and to ultimately stop bleeding. Contraction of the clot increases its density, allowing it to oppose the flow of blood. 
     It is desirable to measure the surface adhesion and contractile functions of blood in order to distinguish normal hemostasis from disease states, and the identification such disorders allow for the proper application of therapy. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an illustration of a downwardly directed displacing force applied by a clotting blood sample to a wetted portion of a probe in passive contact with the clotting blood sample. 
         FIG. 2  is an illustration of an embodiment of an apparatus of the present invention for determining the capacity of a blood sample to clot. 
         FIG. 3  is the illustration of the apparatus of  FIG. 2  after a spring element supporting a wetted portion of a probe of the apparatus is deformed from an original configuration by a downwardly contractile displacing force applied by a blood sample to the wetted portion of the probe. 
         FIG. 4  is an illustration of an alternative embodiment of an apparatus of the present invention for determining the capacity of a blood sample to clot with an integral spring element of the probe disposed in a cantilever mode. 
         FIG. 5  is the illustration of the apparatus of  FIG. 4  after a support arm of the probe supporting the wetted portion of the probe of the apparatus is resiliently deflected downwardly in a cantilever mode from the original undeflected position of  FIG. 4  by a downwardly directed contractile displacing force applied by a clotting blood sample to the wetted portion of the probe. 
         FIG. 6  is an illustration of an alternative embodiment of an apparatus for determining the capacity of a blood sample to clot with an external spring element disposed in an original configuration intermediate the probe and a probe support. 
         FIG. 7  is the illustration of the apparatus of  FIG. 6  after the external spring element supporting a support arm of the probe of the apparatus is elastically deformed from the original configuration by application of a downwardly contractile displacing force applied by a clotting blood sample to the wetted portion of the probe. 
         FIG. 8  is an elevational view of an embodiment of an apparatus for determining the capacity of a blood sample to clot, the apparatus including a variable capacitance displacement sensor. 
         FIG. 9  is an enlarged view of a portion of the variable capacitance displacement sensor of the apparatus of  FIG. 8  showing a pair of adjacent fins supported on a moving assembly of the displacement sensor and a fin supported on a stationary assembly of the displacement sensor disposed intermediate the fins of the moving assembly in an original position. 
         FIG. 10  is the enlarged view of  FIG. 9  after the pair of fins of the moving assembly are displaced downwardly relative to the fin of the stationary assembly by a contractile force applied by the clotting blood sample to the wetted portion probe. 
         FIG. 11  is an enlarged view of a portion of the displacement sensor of  FIG. 8  showing a spring element disposed intermediate a plurality of probe supports and a center mast of the moving assembly of the displacement sensor. 
         FIG. 12  is the view of the spring element of  FIG. 11  after elastic deformation resulting from a clotting blood sample (not shown) being introduced into the well (not shown) of the apparatus of  FIG. 8  and the contractile displacing force being applied by the clotting blood sample to the wetted portion of the probe (not shown) to elastically deform the spring element. 
         FIG. 13  is an elevational view of an alternative embodiment of an apparatus for determining the capacity of a blood sample to clot, the apparatus including an alternate version of a variable capacitance type displacement sensor. 
         FIG. 14  is an enlarged view of a portion of the variable capacitance displacement sensor of the apparatus of  FIG. 13  showing a pair of upwardly extending stationary fins and an adjacent pair of downwardly extending stationary fins supported on a lateral support of a stationary assembly of the displacement sensor with a downwardly extending moving fin and an upwardly extending moving fin supported on a moving assembly of the displacement sensor. 
         FIG. 15  is the enlarged view of  FIG. 14  after the upwardly extending fins and the downwardly extending moving fins of the moving assembly are displaced downwardly to a displaced position as a result of a displacing force being applied to the wetted portion of the probe (not shown) by a clotting blood sample (not shown). 
         FIG. 16  is an enlarged view of one of the spring elements and a pair of probe supports of the apparatus of  FIG. 13  supporting a center mast (not shown) of the variable capacitance displacement sensor. 
         FIG. 17  is the enlarged view of the spring element of  FIG. 16  after deflection by a displacing force applied to the wetted portion of the probe (not shown) by a clotting blood sample introduced into the well (not shown) of the apparatus. 
         FIG. 18  is an enlarged view of a spring element for supporting a wetted member of an embodiment of the apparatus of the present invention having pivoting probe supports to accommodate deflection of the spring element as a result of a displacing force being applied to the wetted portion of the probe. 
         FIG. 19  is enlarged view of the spring element of  FIG. 18  after deflection of the spring element causes the pivoting probe supports to rotate from their original positions. 
         FIG. 20  is a plan view of an alternative embodiment of an apparatus of the present invention to determine the capacity of a blood sample to clot, the apparatus including an eddy current type displacement sensor. 
         FIG. 21  is an illustration of a pair of opposed cantilevered spring elements of the type that may be used in embodiments of the apparatus of the present invention. These spring elements are illustrated in an original position prior to downward displacement of a wetted portion of a probe supported by the spring elements. 
         FIG. 22  is the illustration of the pair of opposed cantilevered spring elements of  FIG. 21  after the cantilevered spring elements are elastically deformed in a manner that would occur if the metal target of  FIG. 23  is downwardly displaced relative to the coil support by a displacing force applied to the wetted portion of the probe (not shown) of the apparatus by a clotting blood sample (not shown). 
         FIG. 23  is an elevation view of the embodiment of the apparatus of  FIG. 20  showing the metal target disposed underneath the coil and the coil support and in close proximity to the coil so that the eddy currents produced as a result of a current from the current source coupled to the coil are affected by the proximity of the metal target to the coil. 
         FIG. 24  illustrates a probe of an embodiment of the apparatus of the present invention having an exterior surface and a wetted portion contacted by a blood sample below an interface. 
         FIG. 25  illustrates a probe of an embodiment of the apparatus of the present invention having an exterior surface and a wetted portion immersed in a blood sample below an interface. 
         FIG. 26  illustrates a probe of an embodiment of the apparatus of the present invention having a corrugated exterior surface and a wetted portion immersed in a blood sample below an interface. 
         FIG. 27  illustrates a probe of an embodiment of the apparatus of the present invention having a conical exterior surface and a wetted portion immersed in a blood sample below an interface. 
         FIG. 28  is an elevation view of an embodiment of the apparatus of the present invention that includes a well disposed on a base, a chuck for supporting the probe within the well and an optical instrument type displacement sensor. 
         FIG. 29  is an enlarged sectional view of the well of  FIG. 28  and of a vial disposed therein intermediate the well and a blood sample with a cantilevered probe supported within the well. 
         FIG. 30  is a perspective view of an embodiment of the apparatus of the present invention having a cantilevered probe support, a chuck releasably supporting a wire portion of the cantilevered probe, a well surrounding the vial (not shown) therein and a microelectromechanical (MEMS) device type displacement sensor engaging a wire portion of the probe and providing a signal corresponding to the sensed displacement of the probe to a piezoelectric adjustable positioning stage. 
         FIG. 31  is a plot of derived displacement of the wire portion of the probe of the embodiment of the apparatus of  FIG. 30  versus displacement sensed by the piezoelectric adjustable positioning stage. 
         FIG. 32  is a graph of the contraction signal generated by the MEMS device of  FIG. 31  to indicate the force applied by a contracting blood sample to the wetted portion of the probe, versus time, in seconds, for human whole blood samples analyzed in an embodiment of the apparatus of the present invention. 
         FIG. 33  is a graph of the force, in micronewtons, imparted to a wetted portion of a probe (shaped like a plate shown in  FIG. 29 ) by the clotting blood sample disposed intermediate the plate and a lower member of the embodiment of the apparatus illustrated in  FIG. 29  versus time, in seconds. 
         FIG. 34  is a graph of the force imparted by a clotting blood sample to the probe versus time, in seconds, for blood samples containing varying components that influence the clotting of the blood sample. 
         FIG. 35  is a graph illustrating the effects of dilution of human whole blood samples having a platelet count of 195,000 platelets/μL with platelet-poor plasmas of varying platelet counts. 
         FIG. 36  is a graph of stress versus strain, indicating the elastic modulus for samples of clotting human whole blood. 
         FIG. 37  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of sodium azide. 
         FIG. 38  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in platelet-rich plasma caused by various concentrations of sodium azide discussed above in relation to  FIG. 37 . 
         FIG. 39  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of cytochalasin D. 
         FIG. 40  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of cyanide. 
         FIG. 41  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of tetrazole. 
         FIG. 42  is a high-level flowchart illustrating the steps of an embodiment of a method of the present invention for detecting a reduction in the contraction force imparted to a probe having a wetted portion contacted by a sample of blood obtained from a patient. 
     
    
    
     SUMMARY OF THE PRESENT INVENTION 
     Some embodiments of the present invention relate to an apparatus to measure clotting in a blood sample comprising a well to receive a sample of the blood, a probe connected at a support arm at the first end of the probe to a probe support secured in a position relative to the well and having a second end with a wetted portion to be contacted by the blood sample to be tested. The probe support supports the wetted portion of the probe at least partially within the well to contact the blood sample received into the well for testing. 
     A blood sample introduced into the well contacts the wetted portion of the probe. The probe is passive; that is, the probe is not driven to rotate, reciprocate or oscillate relative to the well, and the well in which the blood sample is introduced for testing does not rotate, reciprocate or oscillate relative to the probe. A blood clot forms within the stagnant blood sample introduced into the well, and the clotting blood sample adheres to the contacted wetted portion of the probe and it contracts as it clots. The adherence of the blood clot to the wetted portion of the probe contacted by the blood sample is attributable to fibrins forming in the clotting blood sample, and contraction of the blood clot is driven by platelets present in the clotting blood sample. As a result of the clotting of the blood sample, fibrins adhere to an interior surface of the well and to the exterior surface of the wetted portion of the probe that is contacted by the blood sample. As platelets contract, the contracting platelets pull the fibrins to apply a downwardly directed displacing force to the wetted portion of the probe. That downwardly directed force is conveyed through the probe to a probe support. It will be understood that there must be an equal and opposite upwardly directed force applied to the probe to balance the downwardly directed displacing force applied to the wetted portion of the probe by the clotting blood sample. As a result of the application of the displacing force imparted to the wetted portion of the probe, the wetted portion of the probe is displaced downwardly within the well relative to the probe support. The magnitude of the displacement of the wetted portion of the probe can be detected optically, visually and/or electronically and it may be observed, measured and/or correlated to the capacity of the blood sample introduced into the well to clot. 
     It will be understood that preferred embodiments of the present invention include a plurality of electronic devices for measuring the magnitude of displacement of the wetted portion of the probe resulting from the downward force applied by the clotting blood sample. Certain electronic devices included in these preferred embodiments of the apparatus and method of the present invention provide improved sensitivity and accuracy and enable favorable miniaturization of embodiments of the apparatus. While optical displacement sensors, variable capacitance displacement sensors, microelectromechanical device type displacement sensors and varying eddy current displacement sensors are discussed herein below in connection with embodiments of the apparatus and method of the present invention, it will be understood that other electronic devices may be used to detect and/or to measure the displacement of the wetted portion of the probe resulting from contact with a clotting blood sample. 
     In one embodiment of an apparatus and method of the present invention, one or more spring elements are disposed intermediate the wetted portion of the probe and a probe support. A spring element used in an embodiment of the apparatus or method of the present invention elastically deforms according to a spring constant in response to the downwardly directed displacing force applied to the wetted portion of the probe by the clotting blood sample. In some embodiments of the apparatus of the present invention, a plurality of spring elements are disposed intermediate the wetted portion of the probe and the probe support. The plurality of spring elements may together elastically deform according to their collective spring constants in response to a downwardly directed displacing force applied to the wetted portion of the probe by a clotting blood sample. Spring elements that can be disposed intermediate the wetted portion of the probe and the probe support in embodiments of apparatus of the present invention include, but are not limited to, coil springs, which may be referred to as helical springs, beam springs, cantilevered springs and folded cantilever springs, and springs may be integral with the probe, such as cantilevered spring elements. It will be understood that an alternative spring element can also use a captured volume of gas to temporarily store energy while presenting a predictable and determinable resistance to displacement of the wetted portion of the probe. A spring element, as that term is used herein, includes all mechanical devices for storing energy and producing some associated amount of elastic deformation as a result of the storing of energy within the spring element. 
     Embodiments of an apparatus and method of the present invention may include the use of devices used for measuring the displacement of the wetted portion of the probe as a result of the downwardly directed displacing force applied to the wetted portion by a clotting blood sample. In one basic embodiment of an apparatus and method of the present invention, an optical instrument displacement sensor is disposed laterally to the probe. A light source such as, for example, but not by way of limitation, a light emitting diode (LED), may be provided to enable the optical instrument displacement sensor to be used for observing and measuring the deflection and/or the displacement of the wetted portion of the probe relative to a fixed object such as, for example, the probe support or the well. The deflection of the spring element relative to the probe support can be measured and correlated to a displacing force imparted to the wetted portion of the probe by the clotting action of the blood sample. In another embodiment of the apparatus of the present invention, an optical instrument may be used along with a laser light source to impinge on a portion of the probe both before and after the application of the displacing force by the clotting blood sample. In another basic embodiment of the apparatus of the present invention, an optical instrument and a laser light source may be used along with one or more mirrors to reflect and redirect the laser light from the laser light source to magnify the displacement of the probe to enable improved measurement accuracy. 
     One embodiment of the apparatus and method of the present invention comprises a well to receive the blood sample, a probe support secured in a position relative to the well, a spring element coupled intermediate the probe support and a wetted portion of the probe supported within the well, and an optical instrument displacement sensor disposed laterally to at least one of the wetted portion of the probe and the spring element, wherein the introduction of a volume of a blood sample into the well wets the exterior surface of the wetted portion of the probe and wherein the clotting within the blood sample imparts a downwardly directed displacing force to the wetted portion of the probe that results in a displacement of the wetted portion of the probe relative to the probe support resulting in deformation of the spring element. The displacement of the wetted portion of the probe is measured using the optical instrument displacement sensor, and the measured displacement is correlated to the capacity of the blood sample to clot. 
     One embodiment of the apparatus and method of the present invention further includes a well having an interior surface that is treated and/or conditioned to one of promote and impair the adherence of the clotting blood sample to the interior surface of the well as it clots. For example, but not by way of limitation, an embodiment of the apparatus and method of the present invention may include a wetted portion of the probe having an interior surface that is manufactured, shaped, treated and/or conditioned to promote adherence of the blood sample to the wetted portion of the probe as it clots. As a further example, an embodiment of the apparatus and method of the present invention includes an interior surface of the well that provides a surface with undulations and/or roughness to promote adherence of the clotting blood sample to the well. As a result of the roughened or undulating surface on the interior of the well, the clotting blood sample may remain in adherence with the well and the displacing force applied to the wetted portion of the probe by the clotting sample of blood may be maximized. 
     Another embodiment of the apparatus and the method of the present invention includes a well having an interior surface that is treated and/or conditioned to limit the adherence of the clotting blood sample to the interior surface of the well as it clots. For example, an embodiment of the apparatus and method of the present invention may include an interior surface of the well that is manufactured, treated and/or conditioned to provide an exceedingly smooth surface to which the clotting blood sample deposited into the well can adhere. As a result of the smooth surface on the interior of the well, the clotting blood sample may adhere to both the wetted portion of the probe and the interior surface of the well, and the clotting blood sample may become detached from the interior surface of the well at a point at which the capacity of the clotting blood sample to adhere to the smooth interior surface of the well is overcome by the contractile forces acting between the blood clot and the wetted portion of the probe. These contractile forces may, if sufficient, suddenly displace the blood clot from the adhered position with the smooth interior surface of the well and towards the wetted portion of the probe that is contacted by the clotting blood sample. It will be understood that the measure of the force and/or displacement at which the blood clot detaches from the smooth interior surface of the well can be measured and correlated to provide indications of the capacity of the blood sample to adhere during clotting to a surface having a known roughness. This embodiment of the apparatus and method of the present invention can be especially useful for testing the capacity of fibrinogens in the blood to adhere to structures during the clotting process. 
     It will be understood that the interior surface of the well, like the exterior surface of the wetted portion of the probe, in embodiments of the apparatus and method of the present invention, may be manufactured, treated or conditioned to enhance the suitability of the well and the wetted portion of the probe for the type and mode of the testing being performed on a blood sample, and that these components may be adapted to together enable testing of the capacity of a blood clot to generate and impart a maximum displacing force (e.g., conditioning the exterior surface of the probe and/or the interior surface of the well to promote adherence of a clotting blood sample) or to measure the capacity of a blood clot to adhere to a structure (e.g., conditioning the exterior surface of the probe and/or the interior surface of the well to promote a sudden failure of adherence and release of the component from the clotting blood sample). 
     One embodiment of the apparatus of the present invention includes a probe having a radially enlarged wetted portion to enhance the downwardly directed displacing force that is imparted to the wetted portion of the probe by the clotting blood sample. One embodiment of the apparatus of the present invention includes a wetted portion of a probe having a radially enlarged portion that is one of bulbous, disc-shaped (plate-shaped), rounded and frusto-conical in shape. 
     One embodiment of the apparatus of the present invention includes a spring element that is integral with the probe. A probe may include a wire portion as a support arm that extends from a probe support in a cantilevered mode. In this embodiment, the wire portion, which may be referred to as a support arm, is deflected in a cantilever mode by the downwardly directed displacing force applied by the clotting blood sample to the wetted portion of the probe. One embodiment of the apparatus of the present invention includes a probe support having a wire portion or support arm extending from the probe support in a cantilevered mode to a non-linear or angled portion of the probe that is positioned over the well into which the blood sample is introduced. The non-linear or angled portion is intermediate the wetted portion of the probe and the probe support. The wire portion or support arm, which acts as an integral spring element, is deformed in a cantilever mode according to the magnitude of the displacing force applied to the wetted portion of the probe by the clotting blood sample introduced into the well. 
     One embodiment of the apparatus of the present invention includes a probe support having a more rigid wire portion or support arm with a pivoting member such as, for example, a hinge disposed intermediate the wire portion or support arm and the wetted portion of the probe. This rigid wire portion or support arm is not integral with the spring element as is the support arm that can be deflected from its original shape by application of force to the wetted portion of the probe, and the apparatus may include an external spring element disposed intermediate the probe and the probe support. 
     One embodiment of the apparatus of the present invention includes a well that is disposed on or within a tray or base that is connected to the probe support. The tray or base can support other components of the apparatus, and the tray or base can include a well that is integral to the tray for receiving an introduced blood sample. Other embodiments of the apparatus of the present invention may include a well having a plurality of inserts having differing interior surface roughness, differing interior surfaces or surface treatments or differing surface agents applied thereto for conditioning the well. 
     One embodiment of the apparatus of the present invention includes a probe support having a resiliently flexible support arm with a stationary first end coupled or connected to the probe support and a movable second end extending over the well to support the wetted portion of the probe within the interior of the well. The flexible support arm, which is preferably a wire portion, is itself a spring element (integral spring element) so that the application of a displacing force to the wetted portion of the probe by the clotting blood sample in the well deflects at least a portion of the support arm from an original position and shape to a deflected position and an elastically deformed shape. One embodiment of the apparatus of the present invention includes a wetted portion of the probe that is pivotally coupled to a support arm of a probe support that is made of a wire portion having a known spring constant. One embodiment of the apparatus of the present invention includes a wetted portion of the probe supported by a spring element to resist downward displacement of a wetted portion of the probe resulting from the application of a displacing force by the contraction of a clotting blood sample introduced into the well. 
     The present invention further comprises a method of measuring the capacity of the blood to clot. One embodiment of the method of the present invention comprises providing a well to receive the blood sample, providing a probe support in a fixed position relative to the well, providing a probe having a wetted portion with an exterior surface supported from the probe support with the wetted portion at least partially within the well, disposing a spring element one of intermediate the probe and the probe support and integral with the probe, coupling the probe to one of the spring element and the probe support to support the wetted portion of the probe at least partially within the well, disposing a displacement sensor, such as, for example, an optical instrument laterally to one of the spring element and the probe, introducing a volume of a blood sample into the well to wet the exterior surface of the wetted portion of the probe, and using the optical instrument to measure the displacement of the probe resulting from the application of a displacing force to the wetted portion of the probe and resulting from the contraction of the clotting blood sample, wherein the measured displacement of the probe indicates the capacity of the blood sample to clot. Alternately, the displacement sensor may be a microelectromechanical device displacement sensor that engages a portion of the probe, measures the displacement of the portion of the probe and produces a signal corresponding to the sensed displacement. 
     Embodiments of the apparatus and method of the present invention provide for the reliable and accurate measurement of platelet activity in the blood. The capacity to measure platelet activity provides clinically significant implications for patients with conditions causing dysfunctional coagulation of the blood. For example, but not by way of limitation, the capacity to measure platelet activity can be used to guide blood product administration in a hemorrhaging patient, to inform the pharmacologic plan for the patient with coronary artery disease or to characterize the effect of clinically relevant anti-platelet drugs like, for example, aspirin, and can define an individual patient&#39;s response to these drugs or the status of the patient&#39;s recovery when these drugs are withheld. Embodiments of the apparatus and method of the present invention enable the measurement and characterization of energy conversion within and forces generated by platelets during the blood clotting process. 
     Embodiments of the apparatus and method of the present invention have also been used to confirm basic properties known to be associated with blood coagulation. Platelet energetics offer unique biologic signals that have in the past proven to be difficult to measure. These unique biologic signals can be identified, characterized and accurately measured using embodiments of the apparatus and method of the present invention, and this information can be used to reliably identify compounds or therapies that either accelerate or inhibit platelet metabolism, fostering a much better understanding of measured energetic signals such as, for example, platelet respiration and oxygen consumption. This information is easily translatable to characterize the systemic physiology of a patient and it is a reliable indicator of systemic mitochondrial health and platelet energetics. 
     Embodiments of the apparatus and method of the present invention may also be used to provide for early diagnosis of the development of, among other conditions, sepsis in a patient. More specifically, embodiments of the apparatus and method of the present invention may be used to detect a reduction in the energy conversion in, and the resulting contraction forces developed during, coagulation of a blood sample obtained from a patient of interest. 
     Other embodiments of the apparatus and method of the present invention provide for the diagnosis of sepsis in a patient. For example, but not by way of limitation, an embodiment of the method of the present invention comprises the steps of: 1) obtaining a blood sample from a patient; 2) using an embodiment of one of the apparatus and method of the present invention for measuring forces generated within a clotting blood sample taken from the patient; 3) comparing the measured forces detected within the blood sample to the measured forces detected within one of a blood sample previously obtained from the patient and a blood sample obtained from a different patient known to be free of sepsis or other mitochondrial dysfunction that affects clotting; and 4) detecting a reduced capacity of the blood sample to generate forces during contraction resulting from blood coagulation. If the detected reduced capacity of the blood sample to generate forces during contraction resulting from blood coagulation indicates a sufficient reduction in the amount of force developed within the blood sample taken from the patient of interest during contraction resulting from coagulation of the blood sample, the patient can be diagnosed with sepsis. 
     Still other embodiments of the apparatus and method of the present invention provide for the diagnosis of sepsis, a mitochondrial dysfunction or a mitochondrial disorder in a patient of interest. For example, but not by way of limitation, an embodiment of a method of the present invention comprises the steps of: 1) obtaining a blood sample from a patient; 2) using an embodiment of one of the apparatus and method of the present invention for measuring forces generated within the clotting blood sample taken from the patient; 3) comparing the measured forces detected within the blood sample to the measured forces detected within one of a blood sample previously obtained from the patient and a blood sample obtained from a different patient known to be free of mitochondrial dysfunction and sepsis; and 4) detecting a reduction in the force developed during contraction resulting from coagulation of the blood sample obtained from the patient as compared to the force developed during coagulation of one of a previously obtained blood sample from the patient and a blood sample obtained from a person known to be free of sepsis and mitochondrial dysfunction disorders. Mitochondrial dysfunction disorders that can be detected using embodiments of the method include, but are not limited to, cancer, neurodegeneration, diabetes and ischemia/reperfusion injury such as those resulting from, for example, myocardial infarction and stroke, acute inflammatory conditions, chronic inflammatory conditions, cardiogenic shock, Alzheimer&#39;s disease, Huntington&#39;s disease, schizophrenia, migraine headaches, Parkinson&#39;s disease and Down syndrome. 
     The ease of obtaining a small volume of a patient&#39;s blood, combined with the small amount of time needed to use an embodiment of an apparatus or method of the present invention, allows a medical practitioner to obtain multiple blood samples over a recorded time period and to detect, monitor and quantify the development of a pre-shock septic condition. Additionally, these factors enable a medical practitioner to use an embodiment of an apparatus or method of the present invention to detect, monitor and quantify patient improvement as a detected and treated condition or disorder resolves for conditions that are not chronic, such as, for example, but not limited to, sepsis. 
     While not limited by a particular mechanism, embodiment of the apparatus and method of the present invention enable the determination of the total energy produced by platelets during coagulation of a blood sample as indicated by the integral of the force waveform resulting from platelet contractile force. More specifically, the determination of the area under a force curve represents the amount of mechanical work done by and energy produced by the coagulating blood sample. The principle of work-energy equivalence applies to this system as it does to the mechanical equivalent in the more familiar and well-known mechanical work imparted to or by a spring element and as it does to the chemical equivalent of chemical energy (adenosine triphosphate or “ATP”). Mechanical work can be used to store energy within a spring element by energizing the spring element from a relaxed mode to an energized mode or compressed mode. In this energy conversion, work is converted to potential energy, which is stored in the spring element resulting in an increase in the energy within the spring element. The amount of work imparted to the spring element, and the resulting potential energy stored in the spring element, can be quantified by determination of the integral of the equation that relates applied force to displacement of the spring element. In the chemical equivalent, the formation of ATP is the result of the increase in energy in the system resulting from platelet production of ATP. 
     Returning to the mechanical spring equivalent, it is known that the work imparted to a spring element displaced from a relaxed mode to a deflected, compressed or energized mode, where the spring element has a linear spring constant, can be determined as the integral of the equation representing the work imparted to the spring element. For a spring constant of k, in units of Newtons per meter (N/m), the amount of work imparted to a spring element displaced from a relaxed mode to a deflected, compressed or energized mode is analogous to the amount of work yielded by platelets resulting from coagulation of a clotting blood sample. The amount of work stored in a spring element, yielded by a spring element, or yielded by the chemical equivalent of a clotting blood sample, can be determined in terms of the amount of the measured displacement x as: 
         W=∫   0   t   F·vdt=−∫   0   t   kxv   x   dt=− ½ kx   2 .
 
     It will be understood that, in the context of embodiments of the apparatus or method of the present invention, the displacement is the measured movement of a wetted portion of a probe contacted by the clotting blood sample. Integration of the force applied to the wetted portion of the probe by the clotting blood sample directly over time can be done using numerical methods. The spring constant k is dependent on the dimensions of one or more spring elements, such as spring beams in the beam spring, and is known. This integral expresses the amount of energy produced by a given blood sample during the contraction phase of blood clotting and, when normalized by the platelet count, yields information about the global capacity of the patient to utilize energy substrates. Thus, the described highly sensitive embodiments of the apparatus and methods that measure platelet contractile force can also be used to identify mitochondrial dysfunction or sepsis at an early stage. This can be particularly valuable in early detection of sepsis and a pre-shock condition. 
     Sepsis is a condition of the blood that is currently difficult to diagnose before end organ dysfunction is imminent. Sepsis is a health condition that is common, costly to treat and often deadly. Hospitals and medical practitioners often use algorithms to detect potential cases of sepsis and treatment protocol often requires physicians to document patient responses. These algorithms are typically based on the patient&#39;s observed temperature, blood pressure, heart rate and respiratory rate. In particular, a patient&#39;s respiratory rate is a major determinant of the sepsis state and an observable condition that is often poorly documented by medical practitioners and in most hospitals. As a result, what are often considered to be available observable early indications of sepsis generate many false positives, while more specific indications all provide a very late signal which may be learned after the onset of organ dysfunction within the patient. Embodiments of the apparatus and method of the present invention enable a medical practitioner or hospital to obtain a patient&#39;s blood sample and to quickly and inexpensively test the blood sample to detect the onset of sepsis, thereby enabling early diagnosis and treatment of a condition that kills at least 500,000 people or more each year. 
     The capacity of embodiments of the apparatus and method of the present invention to detect and measure platelet contractile force in a patient&#39;s blood sample as an indicator of mitochondrial dysfunction has been confirmed through tests in which platelets were exposed to differing concentrations of inhibitors such as, for example, sodium azide which leads to mitochondrial dysfunction as described in more detail below. 
     Among other advantages, the ease of obtaining a small volume of patient blood in combination with the capacity for rapid use of the of embodiments of the apparatus and method of the present invention enables a medical practitioner or hospital to obtain multiple samples over time, to test the samples, and to thereby monitor the development of a pre-shock septic condition or to monitor patient improvement as the non-chronic disorder such as, but not limited to, sepsis, resolves. 
     The determination of platelet energetics and mechanics provides unique biologic signals requiring distinct devices for measurement. Experiments have proven methods to accelerate or inhibit platelet metabolism, thereby fostering an understanding of measured energetic signals like platelet respiration and oxygen consumption as indicators of systemic physiology of a patient and biomarkers of systemic mitochondrial health including, but not limited to, sepsis patients, hypocoagulable patients and hypercoagulable patients in the hospital and anticoagulated patient at home. However, platelet energetics have proven difficult to measure. Platelet mechanics such as platelet contraction force, contraction rate or clot elastic modulus are readily captured using the device. Platelet dysfunction is often categorized into disease causing metabolic derangements like sepsis or disease causing mechanical dysfunction like von Willebrand disease. 
     Platelet energetics governs global platelet function and the balance of metabolic supply and demand. All biologic processes occurring after platelet activation are energy dependent, susceptible to disorders of mitochondrial function or glycolysis. Changes in energetic processes like mitochondrial function affect an array of measurable signals. For example, sodium azide inhibits the energetic process of oxidative phosphorylation by inhibiting complex IV in the electron transport chain, causing a dose dependent decrease in measured platelet respiration. This mode of inhibition parallels that associated with Alzheimer&#39;s disease where levels of complex IV in the platelet mitochondria are significantly reduced (see, for example,  Platelet Energetics and Mechanics: A Review  by M. J. George, C. E. Wade, C. S. Cox and B. S. Gill). 
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     Embodiments of the apparatus of the present invention can be used to determine the clotting capacity of a sample of blood, and embodiments of a method of the present invention can be used to determine the capacity of a sample of blood to coagulate or clot. 
     Mammal blood clots by forming a network of polymerized fibrins. A circulating monomer called fibrinogen is induced to polymerize into fibrin, which forms the physical clot. Fibrins bind one to the others and form a network of fibrins, or a fibrin skeleton. Increasing fibrin polymerization results in a change in the viscosity of a clotting blood sample and, with increasing fibrin network binding, the clot begins to behave as a solid composite as opposed to behaving as a fluid. The fibrins adhere to the surfaces of structures contacted by the blood sample as it clots. The adherence of the fibrins binds the fibrin skeleton to the structure and, as the clotting progresses and the fibrin skeleton contracts. As a result of the contracting of the fibrin skeleton and adherence of fibrins to contacted structures, a displacing force may be applied to a structure to which the fibrins have adhered. A displacing force resulting from fibrin adherence to the structure can be measured and correlated to the capacity of the blood sample to clot. 
     Embodiments of the apparatus and the method of the present invention provide reliable, repeatable tests of platelet function by measuring the amount of force developed during contraction of a sample of blood during coagulation, thereby yielding a distinct clinical signal in response at varying levels of platelet function as induced by platelet number, the presence of antiplatelet drugs, or an individual patient&#39;s phenotypic variation in platelet function. 
     Although other “platelet assays” have been developed, most have limited clinical application. One reason for this results from attempting to substitute an easily measured quantity as a proxy for overall platelet function. Traditionally, bleeding time is the test done to assess platelet function. The patient is made to bleed and the time it takes to stop bleeding is considered to be an indicator of platelet function. There are currently available several point-of-care platelet assays such as, for example, Plateletworks® (Helena Labs, Beaumont, Tex., U.S.A.) which utilizes cell count after activation, PFA-100/200 (Siemens) which measures the ability of citrated patient blood to close off a fixed opening in a membrane, and VerifyNow® (Accriva Diagnostics) a platelet aggregometer that utilizes changes in optical density that result from the clumping of platelets in a blood sample. However, all of these assays have limitations. 
     There are also assays that are targeted at specific proteins or portions of the clotting process such as, for example, Gp IIb/IIIa receptor binding, but no single step gives a clear indication of the complex, time-evolving process of clot formation. 
     In contrast to these available tests, embodiments of the apparatus and methods of the present invention provide a means of obtaining a detailed representation of platelet function throughout the activation and contraction phases of platelet function. These apparatus and methods are amenable to activation of the clotting process using pharmacological agents to obtain a more rapid result, or can proceed more slowly using only surface activation to initiate clotting to explore the relative effects of adhesion on overall clot function. The extreme sensitivity of the apparatus and methods provided herein allow the detection of small differences in function that are not discernible by currently available tests. 
     This innovative approach improves upon existing platelet assays because it allows the clot to behave in a physiologically relevant way, and the measurement probe and spring allow the actin/myosin machinery to contract through a relatively long linear distance. All three facets of platelet function (adhesion, contraction, signal transduction) contribute to the eventual result, which provides a time-based profile of force generated with very high sensitivity (that is, sub-micronewton sensitivity). 
     There are multiple disorders (such as, but not limited to, uremia, Glanzmann&#39;s thrombasthenia, and others) where platelet counts may be normal but function is clearly impaired as demonstrated by clinically important bleeding. Even a population of otherwise normal individuals will demonstrate a range of response to a given antiplatelet drug; this has been most clearly demonstrated for clopidogrel (Plavix®). These methods also facilitate the transfusion of platelets for the prevention of bleeding complications in thrombocytopenia. Transfusion guidelines utilize a variety of threshold values to trigger platelet transfusion; however, clinicians routinely see patients with values lower than the thresholds for whom no bleeding occurs. This is a clear example of how variable platelet function overrides the simple platelet count in generating clinically important bleeding behavior. These methods allow clinicians to evaluate platelet function as well as count and allow better targeting of expensive platelet transfusions, such as those used routinely in, among others, oncology, neonatology, and trauma resuscitation. 
       FIG. 1  is an illustration of a downwardly directed displacing force applied as indicated by the arrow  25  by contraction of a clotting blood sample  50  to a wetted portion  24  of a probe  20  that is contacted by the blood sample  50 . The wetted portion  24  of the probe  20  may be positioned within the well  30  and the blood sample  50  may be introduced into the well  30  to contact the wetted portion  24  of the probe  20  for testing the capacity of the blood sample  50  to clot, or the blood sample  50  may be introduced into the well  30  and the probe  20  then introduced into the blood sample  50  to wet the wetted portion  24  of the probe  20  to begin the test. The extent of the wetted portion  24  of the probe  20  depends on the volume of the blood sample  50  and the level of the blood interface  52 . Fibrins that form in the blood sample  50  adhere to the interior surface  32  of the well  30  and to the exterior surface  22  of the wetted portion  24  of the probe  20  as the platelets of the blood sample  50  contract during clotting of the blood sample  50 . The adherence of the fibrins to the interior surface  32  of the well  30  and to the wetted portion  24  of the probe  20 , and the contraction of the platelets of the blood sample  50 , result in a downwardly directed displacing force as illustrated by the arrow  25  applied to the probe  20 . This interaction between the clotting blood sample  50  and both of the interior surface  32  of the well  30  and the wetted portion  24  of the probe  20  causes the displacing force applied to the probe  20 . The observation of the displacement of the probe  20  in response to the applied displacing force and the measurement of the displacement enable the determination of the capacity of the blood sample  50  to clot. 
       FIG. 2  is an illustration of an embodiment of an apparatus  10  of the present invention for determining the capacity of a blood sample  50  to clot. The apparatus  10  utilizes the interaction between a clotting blood sample  50  (not shown in  FIG. 2 ) received into a well  30  and a probe  20  having a wetted portion  24  suspended in the well  30  and contacted by a blood sample  50  as illustrated in  FIG. 1 . The apparatus  10  of  FIG. 2  comprises a well  30  having an interior surface  32 , a probe support  29  that is fixed relative to the well  30 , a probe  20  supported from the probe support  29  with at least some of a wetted portion  24  of the probe  20  suspended within the well  30 . The embodiment of the apparatus  10  of the present invention illustrated in  FIG. 2  further comprises a spring element  35  disposed intermediate the probe support  29  and the wetted portion of the probe  20 , an optical instrument  60  displacement sensor disposed laterally to the probe  20  and gradations  62  disposed on a portion of the probe  20  that can be observed using the optical instrument  60 . Optionally, the optical instrument  60  can be supported on the probe support  29  as illustrated in  FIGS. 2-7 . The probe  20  further includes a support arm  28  to couple with and support a spring element  35  that, in turn, supports the wetted portion  24  of the probe  20  within the well  30 . The spring element  35  of  FIG. 2  has an original length  36 . Optionally, the apparatus  10  may further comprise an angled portion  27  intermediate the wetted portion  24  of the probe  20  and the probe support  29 . 
       FIG. 3  is the illustration of the embodiment of the apparatus  10  of the present invention illustrated in  FIG. 2  after a blood sample  50  is introduced into the well  30  to contact at least some of the wetted portion  24  of the exterior surface  22  of the probe  20 . The spring element  35  of the apparatus  10  disposed below the angled portion  27  is illustrated as being elongated from its original length  36  shown in  FIG. 2  to an elastically deformed length  37  due to the application of a downwardly directed displacing force in the direction of arrow  25  by the clotting blood sample  50  to the wetted portion  24  of the probe  20 . The blood sample  50  introduced into the well  30  contacts and adheres to the wetted portion  24  of the exterior surface  22  of the probe  20  and adheres to the interior surface  32  of the well  30 . As clotting of the blood sample  50  progresses, the adherence of fibrins and the contraction of the clotting blood sample  50  imparts the displacing force drawing the wetted portion  24  of the probe  20  towards the interior  32  of the well  30 . The amount of deformation of the spring element  35  from the original length  36  illustrated in  FIG. 2  to the deformed length  37  illustrated in  FIG. 3  is a function of the magnitude of the displacing force applied to the wetted portion  24  of the probe  20  by the clotting of the blood sample  50  and of the spring constant of the spring element  35 . The size, the shape and surface area of the wetted portion  24  of the probe  20  affect the magnitude of the displacing force applied to the wetted portion  24  of the probe  20  by the clotting of the blood sample  50 . The optical instrument  60  displacement sensor may be used to determine the displacement of the wetted portion  24  of the probe  20  as a difference between an originally aligned gradation  62  and a gradation  62  that is aligned after downward displacement of the probe  20 . 
       FIG. 4  is an illustration of an alternative embodiment of an apparatus  10  for determining the capacity of a blood sample  50  to clot.  FIG. 4  illustrates an apparatus  10  comprising a well  30  having an interior surface  32  and a probe  20  having a flexible support arm  28 A connected in a cantilevered mode between a probe support  29  and a support stem  26 . An angled portion  27  is disposed within the probe  20  intermediate the support stem  26  and the support arm  28 A. Optionally, the angled portion  27  illustrated in  FIG. 4  is a pivoting angled portion that accommodates a change in the angle of the angled portion  27  as displacement of the wetted portion  24  of the probe  20  occurs. The probe support  29  is fixed relative to the well  30  and a probe  20  supported from the flexible and cantilevered support arm  28 A is suspended within the well  30 . The flexible support arm  28 A of the probe support  29  supports the probe  20  and, at the same time, functions as an integral spring element disposed intermediate the wetted portion  24  of the probe  20  and the probe support  29  because it may be deflected, in a cantilever mode, from its original position shown in  FIG. 4  by a downwardly directed displacing force applied to the wetted portion  24  of the probe  20  by the clotting blood sample  50  (not shown in  FIG. 4 ) introduced into the well  30 . An optical instrument  60  is disposed laterally to the wetted portion  24  of the probe  20  and gradations  62  are provided on a portion of the probe  20  that can be observed using the optical instrument  60 . It will be noted that the original position of the flexible support arm  28 A extending from the probe support  29  is indicated by the dotted line  41 . 
       FIG. 5  is the illustration of the apparatus  10  of  FIG. 4  after a blood sample  50  is introduced into the well  30  to contact a wetted portion  24  of the exterior surface  22  of the probe  20 . The clotting of the blood sample  50  introduced into the well  30  to fill the well  30  up to the blood interface  52  results in a downwardly directed displacing force applied to the probe  20  and to the support stem  26  of the probe  20  in the direction of arrow  25  to cause a downwardly deflection of the support arm  28 A through an angle  21 . The angle  21 , which is the angular difference between the original angular position of the flexible support arm  28 A indicated by the dotted line  41  and the deflected position of the support arm  28 A indicated by the dotted line  42  can be measured and correlated to the properties of the flexible support arm  28 A to determine the magnitude of the displacing force applied to the probe  20  by the clotting blood sample  50 . The magnitude of the displacing force can be correlated to the capacity of the blood sample  50  to clot. Alternately, the optical instrument  60  and the gradations  62  on the probe  20  may be used to determine the displacement of the wetted portion  24  of the probe  20  as a difference between an originally aligned gradation  62  and an adjacent gradation that is aligned with the optical instrument  60  after displacement of the probe  20 . Optionally, a pivoting angled portion  27  such as, for example, a hinge, may be disposed intermediate the wetted portion  24  of the probe  20  and the support arm  28 A to minimize lateral movement of the wetted portion  24  of the probe  20  during deflection of the support arm  28 A through the angle  21 . 
     In the alternative embodiment of the apparatus  10  illustrated in  FIGS. 4 and 5 , the spring element of the apparatus  10  is integral with the support arm  28 A of the probe support  29  and the application of a displacing force in the direction of arrow  25  applied to the wetted portion  24  of the probe  20  by the clotting blood sample  50  produces the downwardly directed deflection of the support arm  28 A. 
       FIG. 6  is an illustration of a second alternative embodiment of an apparatus  10  for determining the capacity of a blood sample  50  to clot.  FIG. 6  illustrates an apparatus  10  comprising a well  30  having an interior surface  32 , a probe support  29  having a rigid support arm  28  that is fixed relative to the well  30 , a probe  20  suspended from the probe support  29  to dispose the wetted portion  24  within the well  30  and an external spring element  35  disposed intermediate the probe support  29  and the probe  20  and, more specifically, intermediate the spring element  35  and an attachment end  23  of the probe  20 . A support stem  26  is disposed intermediate the wetted portion  24  of the probe  20  and the rigid support arm  28 . An optical instrument  60  is disposed laterally to the probe  20  and gradations  62  disposed on a portion of the probe  20  can be observed using the optical instrument  60 . The support arm  28  of the embodiment of the apparatus  10  of  FIG. 6  is pivotally coupled to pivot about a portion  45  of the probe support  29  upon deformation of the spring element  35 . The spring element  35  has an original length  36  as it supports the wetted portion  24  of the probe  20  within the well  30 . Optionally, a pivoting member  27  such as, for example, a hinge, is disposed intermediate the probe support  29  and the wetted portion  24  of the probe  20  to minimize lateral movement of the probe  20  within the well  30 . 
       FIG. 7  is the illustration of the apparatus  10  of  FIG. 6  after a blood sample  50  is introduced into the well  30  up to blood interface  52  to contact a wetted portion  24  of the exterior surface  22  of the probe  20 . The contraction of the clotting blood sample  50  and the resulting adherence of the blood sample  50  to the interior surface  32  of the well  30  imparts a downwardly directed displacing force in the direction of arrow  25 . The rigid support arm  28  of the probe  20  pivots about the portion  45  of the probe support  29  in response to the displacing force and the spring element  35  of the apparatus  10  deforms from its original length  36  (shown in  FIG. 6 ) to a deformed length  37  due to the application of a displacing force to the wetted portion  24  by the clotting blood sample  50 . The deformation of the spring element  35  from the original length  36 , illustrated in  FIG. 6 , to the deformed length  37 , illustrated in  FIG. 7 , will be a function of the displacing force applied to the probe  20  by contraction of the clotting blood sample  50 , the position of the portion  45  of the support arm  28  at which pivoting occurs relative to the angled portion  27  and the attachment end  23 , and the spring constant of the spring element  35 . Alternately, the optical instrument  60  may be used to determine the displacement of the probe  20  as a difference between an originally aligned gradation  62  and of an adjacent gradation aligned therewith after displacement of the probe  20 . The size and shape of the probe  20 , and the size of the wetted portion  24  of the probe  20  also affect the magnitude of the force applied to the probe  20  by contraction of the clotting blood sample  50 . 
     It will be advantageous for embodiments of an apparatus  10  for measuring the capacity of a blood sample  50  to clot to be portable and compact. The components of the embodiments of the apparatus  10  discussed above in connection with  FIGS. 2-7  can be optimized to satisfy the need for miniaturization. It will also be advantageous for embodiments of an apparatus  10  for measuring the capacity of a blood sample  50  to clot to be highly sensitive to very small displacing forces/displacements of any moving components that are displaced by the forces imparted to the probe  20 . The embodiments of the apparatus  10  discussed below are adapted for miniaturization and for reliably sensing displacements of the wetted portion  24  of the probe  20  resulting from forces applied by the clotting blood sample  50 . 
       FIG. 8  is an elevational view of an embodiment of an apparatus  10  of the present invention for determining the capacity of a blood sample  50  to clot. The apparatus  10  of  FIG. 8  includes a well  30  for receiving a blood sample  50 , a probe  20 , a plurality of probe supports  29  and a plurality of spring elements  35  with legs  34  intermediate the probe  20  and the plurality of probe supports  29 . The embodiment of the apparatus  10  of  FIG. 8  includes a variable capacitance displacement sensor  33  disposed intermediate the probe  20  and the plurality of probe supports  29 . The variable capacitance displacement sensor  33  includes a moving assembly  71  having a center mast  76  from which a plurality of moving fins  72  extend and a pair of stationary assemblies  81  from which a plurality of stationary fins  82  extend. The plurality of moving fins  72  supported on the moving assembly  71  are disposed in an interdigitated arrangement with the plurality of stationary fins  82  supported on the pair of stationary assemblies  81 . A current, represented by the positive sign  98  and the negative sign  99 , is applied across the pair of stationary assemblies  81 . This arrangement results in a capacitor that temporarily stores electrical energy in an electric field around the plurality of moving fins  72  and the plurality of stationary fins  82 . Factors affecting the electric field developed as a result of the current being applied include the surface area of the plurality of moving fins  72  and the plurality of stationary fins  82 , the number of the plurality of moving fins  72  and the plurality of stationary fins  82  and the width of the gap between them it will be understood that the greater the surface area, the greater the number of fins and the smaller the gap, the greater the capacitance will be for a given current. 
     The variable capacitance displacement sensor  33  of  FIG. 8  is variable because a small displacement of the plurality of moving fins  72  relative to the interdigitated plurality of stationary fins  82  changes the electronic behavior of the displacement sensor  33  by changing the electronic interaction between the plurality of moving fins  72  relative to the plurality of stationary fins  82 , and the change can be measured and correlated to the displacement of the plurality of moving fins  72  relative to the stationary fins  82 . When there is a non-variable potential across the conductors (e.g., when a capacitor is attached across a steady source of electrical potential such as, for example, a battery), an electric field develops across the dielectric, causing positive charge “+” to collect on one of the plurality of moving fins  72  and the plurality of stationary fins  82  and negative charge “−” to collect on the other of the plurality of moving fins  72  and the plurality of stationary fins  82 . The measurement of the change in the capacitance properties of the sensor  33  as a result of the displacement of the plurality of moving fins  72  and the plurality of stationary fins  82  can be correlated to the magnitude of displacement of the probe  20  and to the capacity of the blood sample  50  to clot. 
       FIG. 9  is an enlarged view of a portion of a variable capacitance displacement sensor  33  of the apparatus  10  of  FIG. 8  showing two pairs of adjacent moving fins  72  supported on a moving assembly  71  intermediate a pair of adjacent stationary fins  82  on a stationary assembly  81  of the displacement sensor  33  with a single stationary fin  82  supported on the stationary assembly  81  in an original position disposed between each member of each pair of moving fins  72 .  FIG. 9  illustrates that a first gap  83  between each moving fin  72  and the adjacent stationary fin  82 , and a second gap  84  between an end  75  of each moving fin  72  and the center mast  76  of the moving assembly  71 . 
       FIG. 10  is the enlarged view as is  FIG. 9  after the pair of moving fins  72  of the moving assembly  71  are displaced relative to the stationary fins  82  of the stationary assembly  81  by contraction of a clotting blood sample  50  (not shown in  FIG. 10 ) to the probe  20  of the displacement sensor  33 . While the gaps  84  between the ends  75  of the stationary fins  82  and the center mast  76  are unchanged by the movement of the moving fins  72 , the stationary fins  82  are no longer equidistant from the adjacent moving fins  72  and the asymmetrical position of the stationary fins  82  relative to the adjacent pair of moving fins  72  are represented by the new gaps  183  and  283  above and below the stationary fins  82 , respectively. This new arrangement alters the electronic performance of the variable capacitance displacement sensor  33  to change from its original performance associated with the positions of the plurality of moving fins  72  and the plurality of stationary fins  82  reflected in  FIG. 9 . The modified electronic performance of the displacement sensor  33  can be measured and correlated to a displacement of the probe  20  of the apparatus  10  that produces the measured change. 
     The plurality of spring elements  35  illustrated in  FIG. 8  as supporting the movable assembly  71  of the apparatus  10  are a plurality of folded beam springs. These spring elements  35  cooperate to accommodate linear movement of the probe  20  and to thereby prevent interference or contact between components of the moving assembly  71  and the stationary assembly  81 . 
       FIG. 11  is an enlarged view of a portion of  FIG. 8  showing a spring element  35  disposed intermediate a plurality of probe supports  29  and a center mast  76  of the moving assembly  71  of the displacement sensor  33  of  FIG. 8 . The center mast  76  of the moving assembly  71  is connected to the probe  20 .  FIG. 11  illustrates an original position of the spring element  35  and the center mast  76  supported thereby. The spring element  35  of  FIG. 11  includes a first leg  38  extending between each probe support  29  and a stabilizer  37  and a pair of second legs  39  extending between the stabilizer  37  and the center mast  76  of the moving assembly  71 . The first legs  38  and the second legs  39  both connect to the stabilizer  37  and to the center mast  76  at generally right angles. 
       FIG. 12  is the view of the spring element  35  of  FIG. 11  after a blood sample  50  (not shown) is introduced into the well  30  (not shown) of the apparatus  10  of  FIG. 8  and a displacing force is applied by the clotting blood sample  50  to the wetted portion  24  of the probe  20  (not shown). The center mast  76 , which is connected to the probe  20 , is displaced downwardly in the direction of arrow  25 . The first legs  38  and the second legs  39  are deformed from their previous configuration to accommodate movement of the center mast  76  relative to the probe supports  29 . 
       FIG. 13  is an elevational view of an alternative embodiment of an apparatus  10  for determining the capacity of a blood sample  50  to clot. The apparatus  10  of  FIG. 13  comprises a well  30  to receive a blood sample  50  up to blood interface  52 , a probe  20  supported with a wetted portion  22  in the well  30  and a variable capacitance displacement sensor  33 . The variable capacitance displacement sensor  33  includes a movable assembly  71  including a center mast  76  connected to the probe  20 , a plurality of lateral supports  77  extending from the center mast  76 , a plurality of moving fins  72  extending upwardly from the plurality of lateral supports  77 , a plurality of moving fins  73  extending downwardly from the plurality of lateral supports, and a plurality of spring elements  35  disposed intermediate the center mast  76  and the probe supports  29 . The apparatus  10  of  FIG. 13  further includes stationary assemblies  81  having a plurality of downwardly extending stationary fins  82  in an interdigitated arrangement with the upwardly extending fins  72  of the moving assembly  71 , and a plurality of upwardly extending stationary fins  83  in an interdigitated arrangement with the downwardly extending fins  73  of the moving assembly  71 . It will be understood that a downwardly directed movement of the moving assembly  71  will further insert the plurality of downwardly extending fins  73  of the moving assembly  71  into the interdigitated positions relative to the plurality of upwardly extending fins  83  of the stationary assembly  81  while, at the same time, withdrawing the plurality of upwardly extending fins  72  of the moving assembly  71  from the interdigitated positions relative to the plurality of downwardly extending stationary fins  82  of the stationary assembly  81 . This asymmetrical impact of movement of the moving assembly  71  on the extent to which the plurality of fins overlap can be used to enhance the sensitivity of the sensor  33  of the apparatus  10  to movement of the probe  20 . 
       FIGS. 8 and 13  include variable capacitance displacement sensors  33  that can be used to detect and measure displacement of the probe  20  resulting from the introduction of a blood sample  50  into a well  30 . For example, but not by way of limitation, the variable capacitance displacement sensors  33  in these embodiments may be charged at a known current, the time required to obtain a predetermined voltage can be measured, and this process can be repeated several times per second before, during and after probe  20  displacement as it is acted upon by contraction of the clotting blood sample  50 . 
       FIG. 14  is an enlarged view of a portion of a variable capacitance displacement sensor  33  of the apparatus of  FIG. 13  showing a pair of upwardly extending moving fins  72  and an adjacent pair of downwardly extending moving fins  73  supported on a lateral support  77  of a moving assembly  71  of the displacement sensor  33  with a downwardly extending stationary fin  82  and an upwardly extending stationary fin  84  supported on the stationary assembly  81  of the displacement sensor  33 . The downwardly extending stationary fin  82  is disposed between a pair of upwardly extending moving fins  72  in an original position, and the upwardly extending stationary fin  84  is disposed between a pair of downwardly extending moving fins  73  in an original position. 
       FIG. 15  is the enlarged view of  FIG. 14  after the downwardly extending moving fins  73  of the moving assembly  71  are displaced to a displaced position as a result of a displacing force being applied to the probe  20  (not shown) by a clotting blood sample  50  (not shown). The displacement of the moving assembly  71  relative to the stationary assembly  71  results in the upwardly extending stationary fin  84  extending further between the downwardly extending moving fins  73  in the interdigitated position and in the upwardly extending moving fins  72  being withdrawn from the straddling position about the downwardly extending stationary fins  82 . The gap  176  between the end  75  of the downwardly extending stationary fin  82  and the lateral support  77  is narrower and the gap  177  between the upwardly extending stationary fin  84  and the lateral support  77  is wider relative to the relative positions shown in  FIG. 14 . 
     The capacitance of a variable capacitance displacement sensor  33  is affected by, among other factors, the amount of surface area between two adjacent fins or plates of a capacitor and the proximity between the fins or plates.  FIG. 15  illustrates how the amount of overlap, or surface area, between the upwardly extending moving fins  72  and the downwardly extending stationary fin  82  has increased, and how the overlap, or adjacent surface area, between the downwardly extending moving fins  73  and the upwardly extending stationary fin  84  has decreased, as a result of the displacement of the probe  20  (not shown) to which the moving assembly  71  is connected. This arrangement may be particularly advantageous for use in a displacement sensor  33  for detecting a small displacement and for producing a signal corresponding to the displacement. It will be understood that, to utilize this effect, the moving assembly  71  may need to be bifurcated (not shown) so that the upwardly extending moving fins  72  are conductively isolated from the downwardly extending moving fins  73 . 
       FIG. 16  is an enlarged view of one of the spring elements  35  of  FIG. 13  supporting a center mast  76  of the variable capacitance displacement sensor  33  (not shown). The center mast  76  of the variable capacitance displacement sensor  33  (not shown) is illustrated as being coupled to the spring element  35  near its center. The spring element shown in  FIG. 16  is a beam spring. 
       FIG. 17  is a view of the spring element  35  of  FIG. 16  after deflection by a downwardly directed displacing force applied to the probe  20  (not shown) by a clotting blood sample  50  (not shown) introduced into the well  30  (not shown) of the apparatus  10 . The center mast  76  of the variable capacitance displacement sensor  33  (not shown) is illustrated as being coupled to the spring element  35  near its center. The spring element  35  shown in  FIG. 17  is a beam spring and is supported by pivoting probe supports  29 . 
       FIG. 18  is an enlarged view of a spring element  35  of  FIG. 13  having pivoting probe supports  29 A to accommodate deflection of the spring element  35 . The pivoting probe supports  29 A are pivoted to enable the probe supports  29 A to rotate as deflection of the spring element  35  occurs. 
       FIG. 19  is a view of the spring element  35  of  FIG. 18  after deflection of the spring element  35  to cause the pivoting probe supports  29 A to rotate from their original positions to accommodate deflection of the spring element  35 . 
       FIG. 20  is a plan view of an alternative embodiment of an apparatus  10  to determine the capacity of a blood sample  50  to clot. ( FIG. 23 , discussed below, is a related elevation view of the apparatus  10  of  FIG. 20 , but with the plurality of cantilevered spring elements  35  removed (except the foot  99  of two of the cantilever spring elements  35 ) from between the target support  90  and the coil support  67  to better reveal the structures of the apparatus  10 .) 
     The embodiment of the apparatus  10  of  FIG. 20  includes a coil support  67  supporting an electrical coil  68  thereon in a stationary position relative to the well  30  (not shown in  FIG. 20 —see  FIG. 23 ) there below. The coil  68  is connected to a current source  66  such as, for example, a battery. The coil  68 , which may be supported near a center of the coil support  67 , and the coil support  67  are together supported by one or more coil support arms  79  that are connected to the well  30  at a first end  87  (not shown in  FIG. 20 —see  FIG. 23 ). The coil support  67  also supports a thigh portion  85  of each of a plurality of cantilevered spring elements  35  secured between the coil support and a metal target  13  in a “crab legged” arrangement.  FIG. 20  shows each of the plurality of cantilever spring elements  35  includes a thigh portion  85  at a first end and a foot  99  at a second end. Only the foot  99  of two cantilever spring elements  35  are shown in  FIG. 23  to better reveal the relative positions of the coil support  67  and the target support  90 . The foot  99  of each of the plurality of cantilever spring elements  35  is coupled to the target support  90  that, in the view of  FIG. 20 , is larger than the metal target  13  connected to the target support  90  at connectors  78 . The metal target  13  is connected to a probe  20  that is suspended within a well  30  (see  FIG. 23 ). The plurality of spring elements  35  illustrated in  FIG. 20  provide for movement of the metal target  13  and the target support  90  of  FIG. 23  relative to the coil  68  and the coil support  67 . 
     It will be understood from  FIGS. 20 and 23  that the coil support arms  79  support the coil  68 , the coil support  67 , the target support  90  and the metal target  13 , and that the metal target  13  is movable relative to the coil support arms  79  and the coil  68  by flexure of the plurality of cantilever spring elements  35 . This arrangement enables the metal target  13  to be displaced relative to the coil  68  and to thereby produce a detectable response in an eddy current produced by the coil  68  upon energization by the current source  66 . At the same time, the embodiment of the apparatus  10  and method illustrated in  FIGS. 20 and 23  eliminates the interference with the displacement of the probe  20  that may in other embodiments be caused by the electrical leads  95  that deliver current from the power source  66  to the coil  68 . With the versions of the variable capacitance displacement sensor of the embodiments of  FIGS. 8 and 13 , the electrical leads connected to provide a current to the variable capacitance displacement sensor (represented by the “positive” and “negative” signs at reference numerals  98  and  99  on  FIG. 8 ), the electrical leads will present an unwanted resistance to the downwardly displacement of the probe  20 . The embodiment of the apparatus  10  and method illustrated in  FIGS. 20 and 23 , however, enables the detection and measurement of the displacement of the probe  20  without impairing the movement of the probe  20  with electrical leads  95 , which extend from the coil  68  to the power source  66 , neither of which are required to move for the apparatus  10  to function. 
     The introduction of a blood sample  50  into the well  30  of  FIG. 23  to contact the probe  20  produces a downwardly displacing force applied to a probe  20  by the clotting blood sample  50 . The metal target  13  is supported from the coil support  67  by the plurality of spring elements  35  (see  FIG. 20 ) disposed intermediate the metal target  13  and the coil support  67 . The coil  68  and the coil support  67  together remain stationary, and eddy currents produced by the coil  68  as a result of the current provided by the current source  66  are detectable by an eddy current sensor  65  positioned in close proximity to the coil  68 . The eddy currents will vary in response to the proximity of the metal target  13  to the coil  68 , thereby enabling the displacement of the probe  20  resulting from the introduction of a blood sample  50  into the well  30  to be detected and measured by correlating changes in the eddy currents detected and measured by the eddy current sensor  65  to the displacement of the probe  20 . 
       FIG. 21  is an illustration of a pair of cantilevered spring elements  35  of the apparatus  10  of  FIG. 20  in an original position prior to the introduction of a blood sample  50  (not shown) into the well  30  (not shown). It will be noted that the metal target  13  that is connected to the probe  20  (not shown) is in an original position with the metal target  13  in very close proximity to the coil  68  on the coil support  67 . 
       FIG. 22  is the illustration of the cantilever spring elements  35  of the apparatus  10  of  FIG. 21  after the coil support  67  (not shown) is downwardly displaced by a displacing force applied to the probe  20  (not shown) of the apparatus  10  by the clotting blood sample  50  (not shown). It will be noted that the cantilever spring elements  35  of the apparatus  10  are together deflected to accommodate the downward displacement of the probe  20  (not shown) and the metal target  13  to which the probe  20  is attached. This movement of the metal target  13  relative to the coil  68  on the coil support  67  results in a variance in the eddy current in the coil  68  that is detectable and measureable by the eddy current sensor  65  disposed near the coil  68 . 
       FIG. 23  is the elevation view of the apparatus  10  of  FIG. 20  with the plurality of cantilever spring elements  35  removed to reveal the relative positions of the metal target  13  and the coil support  67 . It will be noted that the metal target  13  is movable and in close proximity to the coil  67  so that the eddy currents produced when the current source  66  is coupled to the coil  68  are affected by the proximity of the metal target  13  to the coil  68 . The metal target  13  is attached to the probe  20  and moves with the probe  20  as acted upon by the clotting blood sample  50  in the well  30 , and the distance between the stationary coil  68  and movable metal target  13  there below can be detected and measured using ECS circuitry. A signal generator and output circuits may be used to amplify an output signal from the eddy current sensor  65  of  FIG. 20 . In one embodiment of the apparatus  10  and method of the present invention, the coil  68  may be supported on a coil support  67  such as, for example, a multi-layered printed circuit board comprising a ferromagnetic material. The coil  68  may be etched onto the coil support  67  in this embodiment. In one embodiment of the apparatus  10  and method of the present invention, a specific amount of amperage such as, for example, 1 milli-amp (mA), may be required to sustain a given current provided by the current source  66 . As the metal target  13  is moved by the probe  20  and in response to the introduction of a blood sample  50  into the well  30  of the apparatus  10  in  FIGS. 20 and 23 , more or less current may be required to sustain and maintain the 1 mA set point. This is an example of a closed loop feedback circuit that may be used with one embodiment of the apparatus  10  of the present invention. 
       FIGS. 24, 25, 26 and 27  illustrate cross-sections of four alternatively-shaped probes  20  that may be used in embodiments of the present invention. Each of these probes  20  may enhance the displacing force applied to the probe  20  by the clotting of the blood samples  50  used with embodiments of the apparatus  10 . These alternative probes  20  are not meant to be exhaustive of the wide variance of shapes of probes  20  that can be used with embodiments of the apparatus  10  of the present invention, but are instead provided as mere examples of cross-sections of probes  20  that may be used to enhance the displacing force applied to the probe  20  by the clotting and contraction of the blood sample  50 . 
       FIG. 24  illustrates a probe  20  having an exterior surface  22  and a wetted portion  24  contacted by a blood sample  50  below an interface  52 . The probe  20  of  FIG. 24  has a cross-section that is generally bulbous, with the wetted portion  24  being progressively diametrically smaller as it extends deeper into the blood sample  50  in the well  30 . 
       FIG. 25  illustrates a probe  20  having an exterior surface  22  and a wetted portion  24  immersed in a blood sample  50  below an interface  52 . The probe  20  has a cross-section that is generally semi-circular with a domed portion disposed downwardly within the blood sample  50  which, like the probe  20  of  FIG. 24 , also includes a wetted portion  24  being progressively diametrically smaller as it extends deeper into the blood sample  50  in the well. It will be noted that the interface  52  in  FIG. 25  is above the flattened portion  46  on an upwardly disposed surface  47  of the probe  20 . 
       FIG. 26  illustrates a probe  20  having a more complex exterior surface  22  and a wetted portion  24  immersed in a blood sample  50  below an interface  52 . The probe  20  has a staggered cross-section that “steps” radially as it extends deeper into the blood sample  50 , with the wetted portion  24  being progressively diametrically smaller as it extends deeper into the blood sample  50  in the well  30 . 
       FIG. 27  illustrates a probe  20  having an exterior surface  22  and a wetted portion  24  immersed in a blood sample  50  below an interface  52 . The probe  20  has a cross-section that is generally frusto-conical, with the wetted portion  24  being progressively diametrically smaller as it extends deeper into the blood sample  50  in the well  30 . The cross-sections of each of the probes  20  illustrated in  FIGS. 24-27  have more wetted portion  24  surface area below the interface  52  that is disposed downwardly than wetted portion  24  surface area above the interface  52  that is disposed upwardly, and as fibrins forming within the clotting blood sample  50  adhere to the wetted portion  24  of the exterior surface  22  of the probe  20 , this accentuates the displacing force that is applied to the probe  20  in the direction of the arrow  25 . 
     It will be understood that the probes  20  of  FIGS. 24-27  are mere examples of probes  20  that may be used in embodiments of the apparatus  10  of the present invention or to implement embodiments of the method of the present invention, and are not intended to be limiting of the invention. As a general rule, a probe  20  may be shaped to enhance the displacing force applied to the probe  20  by the contraction of the clotting blood sample  50 . For example, a cumulative downwardly disposed surface area of the probe  20  that is contacted by the blood sample  50  may be substantially greater than the cumulative upwardly disposed surface area of the probe  20  that is contacted by the blood sample  50 . 
       FIG. 28  is an elevation view of an embodiment of the apparatus  10  of the present invention that includes a well  30  disposed on a base  11 . The well  30  surrounds a vial  12  (not shown in  FIG. 28 ) that contains a blood sample  50  (not shown in  FIG. 28 ). The well  30  may insulate the vial  12  to prevent unwanted effects of ambient temperature changes. The well  30  may include an embedded closed loop heater (not shown) and/or a thermocouple (not shown) to enable the temperature of the blood sample  50  to be controlled and/or monitored. The well  30  may comprise aluminum or various other materials. The vial  12  may comprise various materials such as, for example, glass, plastic, Pyrex® or other materials, and may be reusable after cleaning or it may be disposable. The apparatus  10  of  FIG. 28  comprises an optical instrument  60  displacement sensor disposed to enable the precise optical measurement of the displacement of the probe  20  resulting from contraction of the clotting blood sample  50  (not shown). The apparatus  10  of  FIG. 28  further comprises a light emitting diode (LED) light source  16  aligned with the probe  20  and the optical element  60  to enable precise detection of small displacement of the probe  20 . 
     The probe  20  of the apparatus of  FIG. 28  is releasably supported by chuck  17  coupled to the probe support  29 . The probe  20  comprises a wire portion  21  that attaches to an enlarged wetted portion  24  (not shown in  FIG. 28 ) supported within the vial  12  (not shown) within the well  30 . The chuck  17  may, for example, be one of rotatable and retractable to grip and releasably grip the wire portion  21  of the probe  20 . The wire portion  21  of the probe  20  may comprise various materials such as, for example, nickel or stainless steel, and may be either reusable after cleaning or disposable. 
       FIG. 29  is an enlarged sectional view of the well  30  of  FIG. 28  and the vial  12  disposed therein. The vial  12  shown in  FIG. 29  contains a lower member  34  which may comprise various materials such as, for example, acrylic, and which may be circular to conform to the vial  12 . The wire portion  21  of the probe  20  is releasably supported by the chuck  17  (not shown in  FIG. 29 ). The probe  20  further includes a wetted member  24  that comprises an enlarged plate  15  that may be circular to conform to the vial  12 . The plate  15  may comprise various materials such as, for example, acrylic, and is supported within the blood sample  50  and in a spaced-apart relationship with the lower member  31 . The wetted member  24 /plate  15  of the probe  20  is supported by the wire portion  21  of the probe  20  below the interface  52  of the blood sample  50  and is submerged within the blood sample  50  adjacent to the lower member  31 . As discussed above in relation to  FIGS. 2-7 , the wire portion  21  of the probe  20  functions as an integral spring element in a cantilever mode. 
       FIG. 30  is a perspective view of an embodiment of the apparatus  10  of the present invention having a probe support  29 , a chuck  17  releasably supporting a probe  20 , a well  30  surrounding the vial  12  (not shown) therein and a microelectromechanical (MEMS) device  19  type displacement sensor that can be used as a substitute for the optical element  60  and the LED source  16  illustrated in  FIG. 28 . The wire portion  21  of the probe  20  penetrates a vertical slot  18  in the well  30  so that downwardly displacement the wire portion  21 , as discussed above in relation to  FIGS. 5 and 7  (see arrow  25  in those drawings) will be unobstructed. The MEMS device  19  type displacement sensor may be secured to the well  30  by a bracket  14  to engage the wire portion  21  of the probe  20  and to measure the displacement thereof resulting from contraction of a blood sample  50 . The MEMS device  19  type displacement sensor detects and measures one of the force imparted to and the resulting displacement of the probe  20  occurring as a result of the contraction of a clotting blood sample  50  (not shown) within the vial  12  (not shown). The MEMS device  19  type displacement sensor generates an electronic signal corresponding to the sensed displacement and/or force and may direct the signal to an adjustable piezoelectric positioning stage  23  or to a processor (not shown). 
     Contraction of the clotting blood sample  50  (not shown in  FIG. 30 ) results in a downwardly directed displacing force applied to the wetted member  23 /plate  15  (not shown—see  FIG. 29 ) and to the connected wire portion  21  of the probe  20  and thereby causes a downwardly directed deflection of the cantilevered wire portion  21  of the probe  20  (within the slot  18 ) through an angle  21  (angle of displacement illustrated in  FIG. 5 ). As an alternative to or in addition to the use of a MEMS device  19 , the angle  21  of deflection of the wire portion  21  may be detected using an LED light source  16  which is attached to the adjustable piezoelectric positioning stage  23 . Alternately, the LED light source  16  illuminates the wire portion  21  of the probe  20  and the downward displacement of the wire portion  21  of the probe  20  is imaged and tracked using an optical instrument  60  such as, for example, a 10× Nikon® microscope that is connected to an image recording device such as, for example, a Hitachi® KP-F120CL digital camera to record and preserve images. The images may be captured periodically such as, for example, at 3 second intervals, using a LabVIEW® edge detection software program. The deflection of the wire portion  21  of the probe  20  can be measured in, for example, pixels using the recorded images. A micro-grid can then be used to calculate the size of a single pixel at the focal length of the lens of the optical instrument  60  and the pixel information can be converted to microns. This data can be stored in a database allowing comparative statistics and further calculations using a processor connected thereto. 
     Returning to  FIG. 29 , the separation of the wetted portion  24 /plate  15  of the probe  20  and the lower member  31  of the apparatus  10  and the surrounding vial  12  can vary. In one embodiment of the apparatus  10  of the present invention, the wetted portion  24 /plate  15  and the lower member  31  are both circular and within the diameter range from 1 mm to 6 mm, and the vial  12  has a 7 mm inner diameter  55 . In one embodiment of the apparatus  10  of the present invention, the volume of the blood sample  50  that is disposed between the wetted portion  24 /plate  15  of the probe  20  and the lower member  31  may be, for example, 27 μL. In one embodiment of the apparatus  10  of the present invention, a thin layer of silicon oil is applied over the interface  52  at the top of the blood sample  50  to prevent unwanted evaporation of any volatile component within the blood sample  50  such as, for example, water. 
     The MEMS device  19  displacement sensor can be used as a force sensor. The force imparted to the probe  20  as a result of platelet contraction within the clotting blood sample  50  can be derived from displacement of the flexible wire portion  21  of the probe  20  (as shown in  FIG. 5 ), as measured using the MEMS device  19 , using the equation governing force generation for displacement of a cantilever: 
         F =(3δ EI )/ L   3  
 
     where F is force, δ is the wire portion  21  displacement, E is elastic modulus of the material of the wire portion  21  (e.g., nickel), I is the moment of inertia of the cross section of the wire portion  21  of the probe  20 , and L is length of the wire portion  21  of the probe  20 . 
     Validation of the force derivation obtained from measurement of the displacement of the wire portion  21  of the probe  20  using the embodiment of the apparatus  10  of  FIG. 30  was verified using a MEMS device  19  type displacement/force sensor in conjunction with the piezoelectric adjustable positioning stage  23 . The resolution of the piezoelectric adjustable positioning stage  23  was determined to be ±0.1 nm with 0.02% positioning accuracy, while resolution of the force sensing MEMS device  19  type displacement/force sensor was determined to be ±0.5 μN with a range of ±10,000 μN. The validation studies were conducted from 0 to 30 microns because this was the range of the average deflection recorded during assays using whole human blood for the blood sample  50 . 
     The MEMS device  19  type displacement/force sensor was connected to the adjustable positioning stage  23  using bracket  14  to allow vertical translation in the z-axis. The tip  19 A of the MEMS device  19  type displacement/force sensor is in contact with the wire portion  21  of the probe  20  at a position along the probe  20  that is distal to the chuck  17 . The measured downward displacement of the piezoelectric adjustable positioning stage  23  caused an equal amount of deflection in the wire portion  21  of the probe  20 , and the MEMS device  19  type displacement/force sensor measured the resultant force in Newtons. The force measured using the MEMS device  19  type displacement/force sensor was recorded and used to derive predicted wire portion  21  deflection, and this predicted deflection was correlated to actual deflection of the piezoelectric adjustable positioning stage  23 . This test design modeled the force that is exerted on the wire portion  21  by a contracting blood sample  50  disposed between the wetted portion  24 /plate  15  of the probe  20  and the lower member  31 . Acrylic was the material used for the plate  15  and the lower member  31  for these tests. 
     Embodiments of the apparatus  10  of the present invention are used to characterize platelet mitochondrial function. One or more samples of human whole blood were collected by a licensed medical doctor from a healthy volunteer known to refrain from the taking of anticoagulant medications such as, for example, aspirin. Written informed consent of the donors was collected under an approved protocol from the Internal Review Board at the UT Health Science Center. Human whole blood was collected, by antecubital venipuncture, into vials  12  containing the anticoagulant sodium citrate (3.8%, applied at a 9:1 blood to citrate ratio). Platelet-rich plasma was then produced by centrifuging human whole blood treated with anticoagulant for 10 minutes at a centrifuge speed for providing 200×g. The resultant plasma suspension and platelet layer were removed, using a pipette, from the packed red blood cells (RBCs) and these platelets were added to whole blood samples. Platelet-poor plasma was then produced by centrifuging platelet-rich plasma for 15 minutes at a centrifuge speed for providing 3000×g, and then by removing the upper two-thirds of the centrifuged sample that contains the platelets. Platelet counts were determined for the samples and they were maintained at room temperature on a tilt-rocker prior to testing. 
     Embodiments of the apparatus  10  of the present invention may also be used to characterize clot contraction. The capacity of embodiments of the apparatus  10  of the present invention to characterize clot contraction properties was demonstrated by doing assays using whole blood, platelet-rich plasma and platelet-poor plasma samples. As a reference, control values were established using whole human blood, at body temperature (37° C.), that had been re-calcified to a concentration of 10 mMol with anhydrous calcium chloride to reinstate clotting ability and to overwhelm the anticoagulant. The test volume was 27 μL; however, to ensure filling of the test chamber and complete immersion within the blood sample  50  of the wetted portion  24 /plate  15  of the probe  20  disposed within the vial  15 , a volume of 250 μL of blood was injected into a vial  15  comprising glass. Data recording began once the wetted portion  24 /plate  15  was lowered into position such that it was immersed within the blood sample  50  and was 1 mm away from the lower member  50 , both of which comprised acrylic. Deflection of the wire portion  21  of the probe  20  typically began after 360 to 480 seconds, and data collection was concluded after 3,600 seconds (1 hour). 
     To demonstrate the ability of the device to characterize clot elastic modulus (or stiffness) properties, after 3,600 seconds (1 hour), the piezoelectric adjustable positioning stage  23  was displaced vertically in an upward direction with micrometer precision and the resulting force imparted was translated to load, in a cantilevered mode, the wire portion  21  of the probe  20 . This loading induced a tensile force in the clotting blood sample  50  that forms between the wetted portion  24 /plate  15  and the lower member  31  within the vial  12 . The resultant clot strain was detected as displacement of the flexible wire portion  21  resulting from contraction of the blood clot  50  and the force imparted to the probe  20 , and images of the displacement were captured using a Hitachi® camera and was recorded at 10 micron intervals. The resultant clot stress was calculated based on the surface area of the wetted portion  24 /plate  15  and the force imparted to the wire portion  21  of the probe  20  resulting from the upwards displacement of the piezoelectric adjustable positioning stage  23 . The slope of the stress versus strain curves were then calculated and the data are presented in line  40  in  FIG. 31 , which illustrates the relationship between the derived displacement of the cantilevered wire portion  21  of the probe  20  of the apparatus  10  of  FIGS. 5, 7 and 28-30 , in microns, versus displacement sensed by the piezoelectric adjustable positioning stage  23 , in microns. 
     It was then demonstrated that the displacement of the wire portion  21  of the probe  20 , in the cantilevered mode illustrated in the referenced drawings, reliably identifies clot contraction forces resulting from platelet activity within the contracting clotting blood sample  50 . The correlation between the displacement induced by the piezoelectric adjustable positioning stage  23  and the derived displacement of the wire portion  21  of the probe  20  based on force as detected by the MEMS device  19  type displacement/force sensor is shown in  FIG. 31 . This value was obtained 5 times, each time using a new probe  20 . The derived displacement of the wire portion  21  of the probe  20  is represented on the y-axis and was calculated from the force recorded by the MEMS device (force sensor)  19  using the equation provided above. Each derived displacement corresponded to an actual displacement set by the piezoelectric adjustable positioning stage  23 . The relation between cantilevered deflection of the wire portion  21  of the probe  20  and energy elastically stored in the deflected wire portion  21  of the probe  20  as a result of the application of force to the probe  20  by contraction of the clotting blood sample  50  was linear, as seen in  FIG. 31 . Variation in the derived wire displacement increased at a rate of about 0.15 microns per micron of deflection of the wire portion  21  of the probe  20 . The linear conformance of the curve was excellent with R 2 =0.999. The maximum standard deviation observed, even at 30 microns of displacement, was 4.6 microns, or 15.3%. This illustrates that the cantilever equation given above is valid within the range of expected deflection that would result from a contracting blood sample  50 . It was also confirmed that actual and predicted displacement of the wire portion  21  of the probe  20  was equal and within the expected range of variation. Induced deflection in the wire portion  21  of the probe  20  was elastic as there was no evidence of creep after the wire portion  21  of the probe  20  had been cycled four times from 0 to 30 microns. 
       FIG. 32  is a graph of the contraction signal, which is the force applied by the contracting blood sample  50  to the probe  20 , versus time, in seconds, for human whole blood samples analyzed in an embodiment of the apparatus  10  of the present invention. The exemplary embodiment of the apparatus  10  (see  FIG. 30 ) was used to produce the contraction signal shown in  FIG. 32 . The same metrics were determined for the following sample assays and, as a group, represent standard ranges of such values for human whole blood samples  50  obtained from healthy persons. In the absence of a clotting blood sample  50  within the embodiment of the apparatus  10  of the present invention, there was a baseline amount of noise in the deflection signal identified as 1 micron, or approximately 130 μN. As shown on  FIG. 31 , the lift-off time (LT)  43  is on  FIG. 32  indicates when platelet contraction begins, and was defined as when the recorded deflection signal exceeds the baseline noise (1 micron). Using this embodiment of the apparatus  10  of the present invention to characterize whole human blood, the lift-off time (LT) occurred at about 462 seconds and the rate of contraction (ROC) was about 4.27 μN/s. Ultimately, the clotting blood sample  50  imparted a maximum contraction force (MCF)  48  of 4,181 μN and the corresponding time-to-maximum (TTM) contraction force  44  was 2,886 seconds. 
       FIG. 33  is a graph of the force, in micronewtons, imparted to the plate  15  by the clotting blood sample  50  disposed intermediate the plate  15  and the lower member  31  of the embodiment of the apparatus  10  illustrated in  FIG. 29  versus time, in seconds. This graph reflects the data obtained during tests designed to gauge the reproducibility of the data obtained using embodiments of the apparatus  10 . Human whole blood from a single donor was analyzed eight times. The conditions included a temperature of 37° C., 10 mMol of CaCl, and 1 mm of separation between the plate  15  and the lower member  31  of the embodiment of the apparatus  10  (see  FIG. 29 ) where the blood sample  50  is disposed for the test. The platelet count of the blood donor&#39;s samples averaged 213,000 platelets/μL. The graph of  FIG. 33  illustrates the results of the tests. These assays were run in a single day and within 9 hours of collection of the blood samples  50  from the blood donor. Increases in blood sample  50  storage time were determined to result in no significant change in platelet contraction kinetics as determined using an embodiment of the inventive apparatus  10 . For a single donor sample, the platelet contraction curve was found to be highly repeatable, with an average standard deviation for the eight assays of ±7.2%. As can be seen on  FIG. 33 , the observed lift-off time (LT) was 450 seconds, ROC was 3.4 μN/s, and maximum contraction force (MCF) was 3,995 μN and time to maximum was 2,643 s. 
       FIG. 34  is a graph of the force imparted by a clotting blood sample  50  to the probe  20 , in micronewtons, versus time, in seconds, for blood samples containing varying components. This graph illustrates the effect of the variance in blood components of the blood samples  50  tested using an embodiment of the apparatus  10  of the present invention. More specifically, the blood samples  50  tested to obtain the data reflected in  FIG. 34  varied by platelet concentrations, with a blood sample  50  of whole human blood having a platelet count of 195,000 platelets/μL (observed data illustrated by line  53 ), a platelet-rich plasma with a platelet count of 200,000 platelets/μL (line  51 ) and platelet-poor plasma with only 20 platelets/μL (line  54 ). These assays were run at 37° C. with 10 mMol concentration of CaCl. 
     As indicated by line  51  of  FIG. 34 , blood clots resulting from platelet-rich plasma blood samples  50  generated higher contraction forces than the contraction forces for whole human blood, which corresponds to line  53  of  FIG. 34 . Even when adjusted for platelet count, the blood samples  50  with platelet-rich plasma (line  51 ) generated a stronger contraction signal in less time (6,646 μN in 1,926 s) as compared to that generated by whole human blood (line  53 ) (4,181 μN in 2,886 s). Blood clots in platelet-rich plasma contracted earlier, as characterized by the leftmost lift-off time (LT) of the line  51 , and faster, as characterized by rate of contraction (ROC), than did the clotting whole human blood, line  53 . Platelet-rich plasma clotting also generated a signal lift-off time (LT) at 186 seconds with a rate of contraction (ROC) of 4.47 μN/s, while the whole blood lift-off time (LT) was 462 s with a rate of contraction (ROC) of 4.27 μN/s). As was anticipated, little or no significant clot contraction force was detected in the platelet-poor plasma blood sample, reflected in line  54 .  FIG. 34  demonstrates the capacity of embodiments of the apparatus  10  of the present invention to reliably characterize the effect of platelet count on the contraction forces generated by clotting human blood. 
       FIG. 35  is a graph illustrating the effects of dilution of human whole blood samples  50  having a platelet count of 195,000 platelets/μL with platelet-poor plasmas of varying platelet counts. Included in the graph of  FIG. 35  to enable comparison is a solid line  56  reflecting the data obtained from testing an undiluted human whole blood sample  50  having 195,000 platelets/μL. The remaining three lines reflect the data obtained as a result of further testing of three differing diluted human whole blood samples  50 , each human whole blood sample being diluted with platelet-poor plasma with a platelet count of only 1,000 platelets/μL. More specifically, a first aliquot of human whole blood sample  50  was diluted by 50% (e.g., one part human whole blood and one part platelet-poor plasma) with platelet-poor plasma to produce a blood sample having 96,000 platelets/μL (line  58 ), a second human whole blood sample  50  was diluted by 75% (e.g., one part human whole blood and three parts platelet-poor plasma) with platelet-poor plasma to produce a blood sample having 50,000 platelets/μL (line  59 ) and a third sample consisting of the platelet-poor plasma (see above—having only 1,000 platelets/μL) (line  57 ). The resulting clot contraction forces were linearly related to the platelet count. The first aliquot (line  58 ) resulted in a 55% reduction in the maximum contraction force (MCF) as compared to the undiluted human whole blood sample and in a rate of contraction (ROC) decreased by 51%. The second aliquot (line  59 ) resulted in a 75.8% reduction in maximum contraction force (MCF) and in a rate of contraction (ROC) decreased by 89%. In the first aliquot, the lift-off time (LT) was not significantly different from that of undiluted whole blood. However, in the second aliquot, the lift-off time (LT) was prolonged to 528 seconds. Neither the 50% nor the 75% dilution demonstrated a change in time-to-maximum (TTM) as compared to that observed in the undiluted whole blood sample. 
       FIG. 36  is a graph of stress versus strain, indicating the elastic modulus for clotted human blood.  FIG. 36  illustrates data relating to the effect of varying concentrations of red blood cells (erythrocytes) within a human whole blood sample  50  (line  63 ) and within a platelet-rich plasma (line  61 ) on the elastic modulus as determined using an embodiment of the apparatus  10  of the present invention. The data was obtained after completion of the clot contraction force assay by application of tensile stress to the clotted blood samples  50  via the flexible wire portion  21  of the probe  20  resulting in the upward translation of the piezoelectric adjustable positioning stage  23 . The resulting strain was calculated based on upward expansion of the clotting blood sample  50  and the height of the clotted blood sample  50  after contraction from a starting height of 1 mm. As shown by  FIG. 36 , the elastic modulus of the clotted blood sample formed by human whole blood having a platelet count of 190,000 platelets/μL was 1991 pascals, the elastic modulus of the clotted platelet-rich plasma having a platelet count of 200,000 platelets/μL was 1015 pascals.  FIG. 36  demonstrates that embodiments of the apparatus  10  of the present invention were used to obtain data showing that the increase in the presence of red blood cells during clot formation enhanced the elastic modulus of the blood clot and thus the strength of the blood clot. 
       FIG. 37  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of sodium azide. An embodiment of the apparatus  10  of the present invention was used to gauge the impact of the varying concentrations of sodium azide in human whole blood, and the data obtained establishes the capacity of the apparatus  10  to identify and characterize the effect of varying concentrations of this inhibitor on normal platelet metabolic function. Clinically relevant correlations were possible with the apparatus as well. 
     For example, but not by way of limitation, sodium azide is an inhibitor of complex IV in the electron transport chain that disrupts the mitochondrial oxidative phosphorylation. When sodium azide is added to a human whole blood sample, it reduces measured platelet respiration in a dose-dependent fashion. In a clinical observation, this mode of inhibition parallels that seen in Alzheimer&#39;s disease where levels of complex IV in the platelet mitochondria are significantly reduced (Valla, J., et al.,  Impaired platelet mitochondrial activity in Alzheimer&#39;s disease and mild cognitive impairment ; Mitochondrion, 2006. 6(6): p. 323-30). Similarly, use of an embodiment of the apparatus  10  of the present invention enabled the dose-dependent reduction in contraction forces associated with increasing concentrations of sodium azide to be quantified. 
       FIG. 37  includes line  93 , which corresponds to the contraction force of a human whole blood sample without sodium azide. Line  96  corresponds to the reduced contraction force resulting from a sodium azide concentration of 10 mMol in the blood. Line  94  corresponds to the reduced contraction force resulting from a sodium azide concentration of 50 mMol in the blood. Line  101  corresponds to the reduced contraction force resulting from a sodium azide concentration of 25 mMol in the blood. Line  102  corresponds to the reduced contraction force resulting from a sodium azide concentration of 100 mMol. 
       FIG. 38  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in platelet-rich plasma caused by various concentrations of sodium azide discussed above in relation to  FIG. 37 .  FIG. 38  includes line  103 , which corresponds to the contraction force of the platelet-rich plasma sample without sodium azide. Line  104  corresponds to the reduced contraction force resulting from a sodium azide concentration of 1 mMol in the platelet-rich plasma. Line  106  corresponds to the reduced contraction force resulting from a sodium azide concentration of 50 mMol in the platelet-rich plasma. Line  105  corresponds to the reduced contraction force resulting from a sodium azide concentration of 10 mMol in the platelet-rich plasma. Line  107  corresponds to the reduced contraction force resulting from a sodium azide concentration of 100 mMol in the platelet-rich plasma. 
     Cytochalasins inhibit the mechanical process of actin polymerization and produce a dose-dependent decrease in measured platelet contraction forces. This effect is clinically similar to that which occurs in patients with Wiskott-Aldrich syndrome and which exhibit mild thrombocytopenia with impaired movements of actin filaments in the cytoskeleton. A number of studies demonstrate that exposure to cytochalasin reduces both the rate and amount of platelet contraction. Platelet overall clot strength after formation was also reduced as was elastic modulus, a measure of clot strength. When cytochalasin D was added to whole blood, an embodiment of the apparatus  10  detected a dose-dependent decrease in clotting force of contraction associated with increasing concentrations of cytochalasin D (e.g., 0.1 uMol, 0.5 uMol, 1 uMol, 50 uMol and 50 uMol) in a whole blood sample. 
       FIG. 39  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of cytochalasin D. Line  109  to the reduced contraction force resulting from a dimethyl sulfoxide (DMSO) 0.02% concentration in the human whole blood. Line  110  of  FIG. 39  corresponds to a cytochalasin D concentration of 0.1 μMol. Line  111  corresponds to a cytochalasin D concentration of 0.5 μMol. Line  111  corresponds to a cytochalasin D concentration of 0.5 μMol. Line  112  corresponds to a cytochalasin D concentration of 1 μMol. Line  113  corresponds to a cytochalasin D concentration of 5 μMol. Line  114  corresponds to a cytochalasin D concentration of 50 μMol. 
     Sodium cyanide is a potent inhibitor of respiration, acting on mitochondrial cytochrome oxidase and uncoupling electron transport resulting in decreased mitochondrial oxidative metabolism. When cyanide was added to whole blood the apparatus  10  of the present invention was able to detect a dose-dependent decrease in clotting force of contraction associated with increasing concentrations of cyanide. 
       FIG. 40  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of cyanide. Line  115  corresponds to human whole blood without cyanide. Line  116  to the reduced contraction force resulting from a concentration of 10 μMol cyanide in the human whole blood. Line  118  to the reduced contraction force resulting from a concentration of 100 μMol cyanide in the human whole blood. Line  117  to the reduced contraction force resulting from a concentration of 25 μMol cyanide in the human whole blood. 
     Tetrazolium dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction is dependent on NAD(P)H-dependent oxidoreductase enzymes. Therefore, reduction of MTT and other tetrazolium dyes depends on the cellular metabolic activity due to NAD(P)H flux which causes a change in color, which is the basis of the MTT assay. The MTT assay is used as a colorimetric assay for assessing cell metabolic activity. 
       FIG. 41  is a graph illustrating the capacity of embodiments of the apparatus of the present invention to characterize metabolic dysfunction in human whole blood caused by various concentrations of tetrazole. Line  120  corresponds to the enhanced contraction force resulting from a concentration of 1 mMol of tetrazole in human whole blood. Line  121  corresponds to the reduced contraction force resulting from a concentration of 60 mMol in human whole blood. 
     Embodiments of the method of the present invention provide for detecting a decrease in the forces generated within a blood sample obtained from a patient that result from energy dysfunction. Cells make energy by using adenosine triphosphate (ATP), often referred to as the “molecular unit of currency.” There are two ways in which ATP can be used in a cell to make energy. These are referred to as glycolysis and oxidative phosphorylation. The loss of energy due to mitochondrial dysfunction reduces the capacity of the blood to clot and thereby reduces the capacity of the clotting blood sample to impart forces to a probe of an embodiment of the apparatus  10  of the present invention. Sepsis results in a number of anomalies and pathologies, one of which is mitochondrial dysfunction. Mitochondrial dysfunction is an indirect indicator of sepsis and is detectable, using embodiments of the apparatus  10  and method of the present invention, earlier than other manifestations of the condition thereby enabling the condition to be addressed through patient treatment at a much earlier stage, which can be critical. 
       FIG. 42  is a high-level flowchart illustrating the steps of an embodiment of a method  122  of the present invention for detecting a reduction in the contraction force imparted to a probe having a wetted portion contacted by a sample of blood obtained from a patient. The purpose of the embodiment of the method  122  is to provide an indication of mitochondrial dysfunction in the obtained blood sample that indicates a blood condition such as, for example, sepsis or some other condition that relates to or may cause mitrochondrial dysfunction. In step  123 , a current blood sample is obtained from a patient for testing. In step  124 , a well to receive the current blood sample obtained in step  123  is provided. In step  125 , a probe having a wetted portion is provided. In step  126 , a probe support fixed relative to the well is provided. In step  127 , the probe is supported using the probe support with at least a portion (the wetted portion) proximal to the well. This step enables the wetted portion of the probe to be contacted by the current blood sample obtained from the patient as will be discussed below. In step  128 , one of an external spring element and a spring element that is integral with the probe is disposed intermediate the wetted portion of the probe and the probe support. In step  129 , a displacement sensor is provided to detect and measure displacement of at least a portion of the probe relative to the well and the probe support fixed relative to the well. In step  130 , a volume of the current blood sample obtained from the patient is introduced into the well to contact the wetted portion of the probe. In step  131 , the displacement sensor is used to measure the displacement of the probe resulting from the contraction of the current blood sample and the resulting force applied to the wetted portion of the probe. In step  132 , the measured displacement of the probe is correlated to the capacity of the obtained blood sample to clot. In step  133 , the measured capacity of the current blood sample to clot is compared to the capacity of one of a blood sample previously obtained from the patient and a blood sample obtained from another known to be free of mitochondrial dysfunction and sepsis to clot. Finally, in step  134 , a reduced capacity of the obtained blood sample to clot is detected. 
     The capacity of embodiments of the apparatus and method of the present invention to identify alterations in clotting activity due to various metabolic inhibitors clearly demonstrates its utility in monitoring mitochondrial dysfunctions as manifested by platelet energetics and mechanics. 
     The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, components and/or groups, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The terms “preferably,” “preferred,” “prefer,” “optionally,” “may,” and similar terms are used to indicate that an item, condition or step being referred to is an optional (not required) feature of the invention. 
     As used herein, the term “patient” or “subject” refers to a living mammalian organism, such as a human or veterinary patient (such as, but not limited to non-human primates, companion animals (dog, cat, etc.), cow, sheep, goat and laboratory animals such as mouse, rat, guinea pig, etc. In certain embodiments, the patient or subject is a primate. Non-limiting examples of human subjects are adults, juveniles and infants. 
     It will be understood that the above discussion is isolated to human blood, but the findings and, in particular, the applications of embodiments of the inventive apparatus and method are applicable to the testing and analysis of blood of animals as well. It should be noted that, in human subjects, a normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Having more than 450,000 platelets is a condition called thrombocytosis, and having less than 150,000 is known as thrombocytopenia. For veterinary subjects a normal platelet count range will vary between genus and even species. For example, in dogs, a normal platelet count generally ranges from 200,000 to 900,000 platelets per microliter of blood and, in cats, a normal platelet count generally ranges from 300,000 to 700,000 platelets per microliter of blood. 
     The corresponding structures, materials, acts, and equivalents of all means or steps plus function elements in the claims below are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description of the present invention has been presented for purposes of illustration and description, but it is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the invention. The embodiment was chosen and described in order to best explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated.