Patent Description:
The process by which the body prevents blood loss is referred to as coagulation. Coagulation involves the formation of a blood clot (thrombus) that prevents further blood loss from damaged tissues, blood vessels or organs. The formation of a blood clot is a complicated process involving a first system comprised of cells called platelets that circulate in the blood and serve to form a platelet plug over damaged vessels and a second system based upon the actions of multiple proteins (called clotting factors) that act in concert to produce a fibrin clot. These two systems work in concert to form a clot and disorders in either system can yield disorders that cause either too much or too little clotting.

Platelets serve three primary functions: (<NUM>) sticking to the injured blood vessel (a phenomenon called platelet adherence); (<NUM>) attaching to other platelets to enlarge the forming plug (a phenomenon called platelet aggregation); and (<NUM>) providing support for the processes of the coagulation cascade (molecules on the surface of platelets greatly accelerate several key reactions).

When a break in a blood vessel occurs, substances are exposed that normally are not in direct contact with the blood flow. These substances (primarily collagen and attached multimeric von Willibrand factor) allow the platelets to adhere to the broken surface. Once a platelet adheres to the surface, it releases chemicals that attract additional platelets to the damaged area, referred to as platelet aggregation. These two processes are the first responses to stop bleeding. The protein-based system (the coagulation cascade) serves to stabilize the plug that has formed and further seal up the wound.

The support role of the platelet to the coagulation cascade is provided, in part, by one of the components on the outside of a platelet, called phospholipids, which are required for many of the reactions in the clotting cascade. The goal of the cascade is to form fibrin, which will form a mesh within the platelet aggregate to stabilize the clot. All of the factors have an inactive and active form. Once activated, the factor will serve to activate the next factor in the sequence until fibrin is formed. The coagulation cascade takes place at the site of a break in, e.g., a blood vessel that has the platelet aggregate. Fibrin forms a mesh that, in concert with the platelets, plugs the break in the vessel wall. The fibrin mesh is then further stabilized by additional factors which cross-linkup the clot (much like forming an intricate network of reinforced strands of fibrin).

In the case of trauma-induced bleeding, it is important to understand very quickly the clotting response of a particular individual in order to apply appropriate therapy to treat bleeding and ensure that the trauma is dealt with appropriately. Defective platelet functions, both primary (adhesive, von Willibrand factor interaction) and secondary (fibrin polymer organization and polymerization, integrin function) are recognized as a particularly important contributor in prolonged non compressible bleeding. The development of hemostatic disorders in trauma patients, and associated progression in hemorrhagic and other shock states, can be due to different factors and thus require different therapies.

Currently, thromboelastography (TEG) is the accepted clinical standard for testing the efficiency of whole blood coagulation. As an example, the related <CIT>, entitled "Portable Coagulation Monitoring Device and Method of Assessing Coagulation Response" discloses a portable coagulation monitoring device typically comprising glass plates used to diagnose trauma-related coagulopathies in the field. Further, current methods of introducing blood into, for example, a test cartridge of coagulation monitoring devices may involve measuring the amount of blood required for a test by using a pipette or other capillary device, for example, and then pipetting the required amount of blood into the test cartridge. Blood introduction and the need for clinical staff to pipette blood is a challenge in point-of-care settings and operating room settings where sterility is important.

<CIT> discloses a portable coagulation monitoring device and method of assessing coagulation response.

The presently claimed invention is as defined in the claims.

The presently claimed invention provides a method of measuring coagulation response in a blood sample, comprising the steps of: a) placing a sample droplet of blood between and in contact with a first surface and a second surface of oppositely disposed glass-filled thermoplastic polymer members, wherein the glass-filled thermoplastic polymer members are optically transparent; b) moving at least one member linearly with respect to the other member at a predetermined speed sufficient to activate platelets through exposure to shear forces; and c) optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the member surfaces in order to measure coagulation response of the droplet of blood.

Suitably, the method may further comprise moving at least one member at a first speed and optically detecting adherence of the sample droplet of blood to the surface of the members to determine platelet response during coagulation.

Suitably, the method may further comprise subsequently moving at least one member at a second speed slower than the first speed, and optically detecting the level of coagulation of the blood sample as indicative of fibrin polymerization response.

The presently claimed invention further provides a test cartridge for use with an optical detection device for measuring coagulation response in a blood sample, comprising a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, and the first member and second member being linearly movable relative to each other, wherein the first and second members comprise a glass-filled thermoplastic polymer, wherein the glass-filled thermoplastic polymer members are optically transparent, wherein the glass constituent in the glass-filled thermoplastic polymer members is configured to activate platelets and induce blood clotting.

Suitably, the test cartridge may be configured to be disposable after use.

Suitably, the test cartridge may further comprise a humidity control mechanism.

Suitably, the humidity control mechanism may comprise a sponge-like pad inside a humidity pouch, and further wherein the humidity pouch comprises a removable cover.

Suitably, the removable cover may be configured to be optionally removed to expose the sponge-like pad to an interior environment of the device.

Suitably, the test cartridge may further comprise a temperature control mechanism configured to maintain a desired temperature within the device.

Suitably, the temperature control mechanism may comprise a heater.

Suitably, the temperature control mechanism may comprise a cooling device.

Suitably, the first member and second member may further comprise engagement features configured to engage with a drive mechanism in the optical detection device.

Suitably, the engagement features may comprise one or more of pinch contact ribs and ridges.

Suitably, the test cartridge may further comprise a receptacle for a blood introduction mechanism, wherein the receptacle is configured to provide a path for the sample droplet of blood to pass form the blood introduction mechanism to a point between the first surface and the second surface.

Suitably, the test cartridge may further comprise the blood introduction mechanism, wherein the blood introduction mechanism comprises an open top; a funnel portion; a flat bottom; and a lip attached to the funnel portion; wherein the open top comprises an opening larger than an opening at the flat bottom, and further wherein the blood introduction mechanism is configured such that a desired amount of blood introduced to the open top may pass through the blood introduction mechanism and into the receptacle of the test cartridge, thereby providing the sample droplet of blood into the device.

Certain aspects of the presently disclosed subject matter having been stated hereinabove, which are addressed in whole or in part by the presently disclosed subject matter, other aspects will become evident as the description proceeds when taken in connection with the accompanying Drawings as best described herein below.

Having thus described the presently disclosed subject matter in general terms, reference will now be made to the accompanying Drawings, which are not necessarily drawn to scale, and wherein:.

The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Drawings, in which some, but not all embodiments of the presently disclosed subject matter are shown.

In one instance, the disclosure provides a device for measuring coagulation response in a blood sample including: a set of test components that include a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, and the first member and second member being linearly movable relative to each other, wherein the first and second members include a glass-filled thermoplastic polymer; a drive mechanism connected to at least one of the first member and the second member for linearly moving the first member and the second member relative to each other in parallel when a blood sample is in contact with the first surface and the second surface; and an optical detection sensor system for detecting interaction of light with a blood sample located between the first member and second member, as an indication of coagulation response of the blood sample.

In some embodiments, the first surface and the second surface are spaced apart from about <NUM> to about <NUM>. Moreover, the glass-filled thermoplastic polymer may be selected from the group consisting of nylon (polyamide), polycarbonate, polypropylene, polyethylene and polyester. The composition of the polymer may include glass beads and/or glass fibers in amounts including glass beads and/or fibers of about <NUM>% to about <NUM>% in some examples, or about <NUM>% in other examples.

In certain other embodiments, at least one of the first or second members may be a rod that can rotate to initiate coagulation. In such examples, the device may further include a third member having a third surface spaced an amount sufficient to allow a sample droplet of blood to contact the surface of the rod and initiate coagulation.

Some aspects of the present disclosure include a blood sample collection cartridge which is removable from the device and within which the test components are housed. This test cartridge may be disposable after use and may further include a memory device for storing data relating to a blood sample tested. The blood sample collection cartridge may also include pinch contact ribs used to securely couple engagement features of the test components with the drive mechanism of the device.

The drive mechanism may be programmed for moving the first member and second member at different speeds relative to each other for detecting different mechanisms involved in a coagulation response of a blood sample. The drive mechanism may include piezo motors or any other suitable driving source. The device may include a microcontroller for controlling operation of the drive mechanism and optical detection sensor system. It may also include a displacement sensor for detecting and controlling the amount of relative movement between the first member and the second member. Further still, the device may include a connection interface module for connecting and communicating between the device and an external system, and an analog to digital converter coupled to the optical detection sensor system for converting analog signals indicative of coagulation response of a blood sample into digital signals for storage thereof. In some instances of the disclosure, the device may also include a temperature control mechanism that may include a heater and/or a cooling device.

The optical detector sensor system may be adapted for detecting binding of the blood sample to the first surface and the second surface as an indication of platelet response during coagulation.

In some embodiments, the first and/or second surface has been treated to induce, slow, or modify the coagulation process for selecting in favor of or against specific aspects of coagulation of the sample. The treatments may optionally enhance or reduce at least one characteristic selected from the group consisting of platelet or blood protein binding, reactivity, and activation. In general, the device is configured for analyzing blood rheology and coagulation of fresh whole blood or some fraction thereof without adding external reagents. The device may also be configured for measuring, with no functional delay, the dynamic balance between pro- and anti-thrombotic hemostatic status by sequential samples from the same person or animal.

In certain other instances of the disclosure, the device may include a first channel and a second channel, wherein the first channel comprises the set of test components, the drive mechanism, and the optical detection sensor system, and the second channel comprises a second set of test components, a second drive mechanism, and a second optical detection sensor system, and further wherein the first and second channels operate independently of one another and enable the device to perform measurements of two blood samples at the same time. The separate channels may be configured to perform distinct measurements that include any one of a thrombelastogram test, a fibrinogen test, a heparin test, and other platelet function test.

In another instance, the disclosure provides a method of measuring coagulation response in a blood sample including the steps of: placing a sample droplet of blood between and in contact with first and second facing surfaces of oppositely disposed glass-filled thermoplastic polymer members; moving at least one member linearly with respect to the other member at a predetermined speed sufficient to activate platelets through exposure to shear forces; and optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the member surfaces in order to measure coagulation response of the droplet of blood. In some aspects, two blood sample collection cartridges are used, wherein the first set of test components are housed in a first cartridge representing part of a first channel and the second set of test components are housed in a second cartridge representing part of a second channel.

In some instances of the disclosure, the device may also include a humidity control mechanism. In one example, the humidity control mechanism may include a sponge-like pad inside a humidity pouch. The humidity pouch may also include a removable cover, thereby enabling the cover to be optionally removed to expose the sponge-like pad to an interior environment of the device.

In a further aspect, the present invention discloses a method of measuring coagulation response in a blood sample including the steps of: placing a sample droplet of blood between and in contact with a first surface and a second surface of oppositely disposed glass-filled thermoplastic polymer members, wherein the glass-filled thermoplastic polymer members are optically transparent; moving at least one member linearly with respect to the other member at a predetermined speed sufficient to activate platelets through exposure to shear forces; and optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the member surfaces in order to measure coagulation response of the droplet of blood.

In some embodiments, at least one member may be moved at a first speed and optically detecting adherence of the sample droplet of blood to the surface of the members to determine platelet response during coagulation. The method may also include subsequently moving at least one member at a second speed slower than the first speed, and optically detecting the level of coagulation of the blood sample as indicative of fibrin polymerization response.

The relative motion between the two members may be controlled to generate arbitrarily selected waveforms to induce desired fluid shear rates at selected amplitudes, frequency, duration, and sequence such that the device is enabled to emulate fluid shear as desired over a broad range including from about DC (zero shear) to shear rates that would cause fluid cavitation and subsequent destruction of the cellular components of the sample, and continuously including all points in the shear rate spectrum between these two points. The shear rate may also be controlled in a sequence of values to generate specific protocols or plate motion paradigms for targeted diagnostic or analytic objectives, wherein such targeted diagnostic or analytic objectives include rapid initiation of primary coagulation, destructive or non-destructive viscoelastic evaluation of early, mid-phase, or late-phase clotting, emulation of clinically-accepted or otherwise recognized shear rate protocols for comparison with other commercial or experimental devices, or validation testing against known standards.

Optical detection may be conducted by transmitting electromagnetic waves into the sample droplet, and detecting at least one of transmission, absorption, reflection and refraction of the electromagnetic waves through the sample droplet at respective light detectors, to generate analog signals representative of coagulation properties of the blood in the sample droplet for primary and secondary coagulation mechanisms. The signals may also be converted to digital signals, stored, and analyzed in a predetermined manner to obtain selected information about the coagulation response of the blood in the sample droplet.

In some embodiments, the method may include moving one member relative to the other member in a manner causing the other member to move due to visco elastic coupling between the blood and the other member; and determining the visco elastic properties of the blood from the movement of the other member. The method may also include detecting strain rates caused by movement of the one member and the other member caused by visco elastic coupling between the one member and the other member caused by the blood sample; and determining the coagulation state of the blood by inference analysis based on visco elasticity of the blood sample determined from mechanical coupling between the two members and the resulting strain rates. The visco elasticity of the blood may be continually measured over time to monitor changes of the coagulation response of the blood.

In a further aspect, the present invention discloses a method of measuring coagulation response in a blood sample according to claim <NUM>, including the steps of: placing a sample droplet of blood between and in contact with facing surfaces of oppositely disposed glass-filled thermoplastic polymer members; moving at least one member linearly with respect to the other member at a first speed; optically detecting a first coagulation response of the blood indicative of platelet response in the blood; moving at least one member linearly with respect to the other member at a second speed; and optically detecting a second coagulation response of the blood indicative of fibrin polymerization.

Other aspects of the present invention include a test cartridge for use with a device for measuring coagulation response in a blood sample that includes a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, and the first member and second member being linearly movable relative to each other, wherein the first and second members comprise a glass-filled thermoplastic polymer, wherein the glass-filled thermoplastic polymer members are optically transparent.

The presently claimed test cartridge may
further include a receptacle in the test cartridge for a blood introduction mechanism wherein the receptacle provides a path for the sample droplet of blood to pass form the blood introduction mechanism to a point between the first surface and the second surface. The blood introduction mechanism may include an open top; a funnel portion; a flat bottom; and a lip attached to the funnel portion; wherein the open top comprises an opening larger than an opening at the flat bottom, and further wherein a desired amount of blood introduced to the open top may pass through the blood introduction mechanism and into the receptacle of the test cartridge, thereby providing the sample droplet of blood into the device. The blood introduction mechanism may also include a solid plug cap attached wherein the solid plug cap sealingly nests within the opening of the open top. The mechanism may further include one or more alignment features disposed on the funnel portion.

In some instances, the presently disclosed subject matter provides portable coagulation monitoring devices, systems, and methods. Namely, the presently disclosed subject matter provides a test cartridge for use in a portable coagulation monitor (PCM) or assay device, wherein the PCM device is for the diagnosis of trauma or other related coagulopathies in which it is important to assess coagulation response to optimize treatment, for example, in critical field situations wherein the first hour is critical in terms of preventing long-term debilitating events or even death.

The presently disclosed test cartridge is typically used in thromboelastigraphy (TEG) and includes, in some embodiments, two plates arranged substantially in parallel with a small gap therebetween for receiving a sample of blood to be tested. The detection of coagulation is done optically by measuring mechanical interaction between the surfaces of the two plates resulting from changes in the viscosity of the sample fluid and binding of the sample fluid to the plate surfaces. The two plates are glass-filled thermoplastic polymer plates in which the surfaces face each other, and are spaced an amount sufficient to allow a relatively small sample of blood to contact the facing surfaces of the two plates at the same time without an air space between. The glass-filled thermoplastic polymer plates are then agitated to induce the platelet clotting process for measurement of blood thromboelastigraphy.

Further, the presently disclosed test cartridge may include a disposable blood introduction device to dose the correct amount of blood into the test cartridge using capillary action, without the need to measure the blood. The disposable blood introduction device may be used to fill the test cartridge with the correct amount of blood and any extra blood in the device may then be safely disposed of with the device. The disposable blood introduction device typically includes a funnel or the like for introduction of the blood into the test cartridge and an outlet to allow blood to move from the funnel into the test cartridge.

Referring now to <FIG>, a simplified block diagram is shown depicting an example of the presently disclosed portable coagulation monitor (PCM) device <NUM> that includes a test cartridge, wherein the test cartridge includes glass-filled thermoplastic polymer plates for measurement of blood thromboelastography and a disposable blood introduction device.

PCM device <NUM> may be used for the diagnosis of trauma or other related coagulopathies in which it is important to assess coagulation response to optimize treatment, for example, in critical field situations wherein the first hour is critical in terms of preventing long-term debilitating events or even death. In one example, PCM device <NUM> is based on the PCM device described with reference to <CIT>, entitled "Portable Coagulation Monitoring Device and Method of Assessing Coagulation Response," ("the '<NUM> Patent"). The '<NUM> Patent describes a device, system and method in which small-volume blood samples may be subjected to shear forces and shear stresses between two parallel planar surfaces to which linear motion trajectories are imparted. The formation of clots or coagulation of the sample is measured from dynamic mechanical coupling which occurs between the two parallel planar surfaces. Detection of the coagulation response can be achieved through optical probing or by measurement of physical effects of the blood sample binding to the planar surfaces, and restricting movement thereof.

In this example, PCM device <NUM> may include one or more of a power source <NUM>, a controller <NUM>, a communications interface <NUM>, a user interface <NUM>, an optics system <NUM>, a temperature control mechanism <NUM>, and a pair of actuators <NUM> (e.g., actuators 118A, 118B). Those skilled in the art will recognize that PCM device <NUM> may include other components, which are not shown, such as, but not limited to, any types of motors, any types of sensors, any types of device-specific drivers and/or controllers, data storage (i.e., volatile and/or nonvolatile memory), and the like.

Further, PCM device <NUM> can be ruggedized to allow for use during impacts and/or vibrations. In one example, PCM device <NUM> may include an internal accelerometer (not shown) that can be used to measure such impacts and/or vibrations and allow PCM device <NUM> to compensate accordingly. PCM device <NUM> may also be designed to be versatile and measure platelet and fibrin clotting over a wide dynamic range of shear. Additionally, PCM device <NUM> can operate on USB hub power as a peripheral device with components that are readily manufactured and assembled.

PCM device <NUM> may also include mechanical features (not shown) for receiving and holding a test cartridge <NUM>, for example, a TEG test cartridge. Namely, test cartridge <NUM> may be a pluggable component of PCM device <NUM>, as shown in <FIG>. Together, PCM device <NUM> and test cartridge <NUM> may be considered a PCM system. More details of an example of the physical instantiation of PCM device <NUM> for receiving and holding test cartridge <NUM> are shown and described hereinbelow with reference to <FIG>.

Power source <NUM> can be, for example, any rechargeable or non-rechargeable battery. In one example, power source <NUM> is a <NUM>-volt battery, rated at about <NUM> mA and with a battery life of about <NUM> hours. In certain other instances of the disclosure, power source <NUM> may be external to the PCM device <NUM>, or may include any suitable internal or external power source.

Controller <NUM> can be any standard controller or microprocessor device that is capable of executing program instructions. Controller <NUM> can be used to manage the overall operations of PCM device <NUM> including those of communications interface <NUM>, user interface <NUM>, optics system <NUM>, temperature control mechanism <NUM>, and actuators <NUM>.

Communications interface <NUM> may be any wired and/or wireless communication interface for connecting to a network (not shown) and by which information may be exchanged with other devices connected to the network. Examples of wired communication interfaces may include, but are not limited to, USB ports, RS232 connectors, RJ45 connectors, Ethernet, and any combinations thereof. Examples of wireless communication interfaces may include, but are not limited to, an Intranet connection, Internet, ISM, Bluetooth® technology, Bluetooth® Low Energy (BLE) technology, Wi-Fi, Wi-Max, IEEE <NUM> technology, ZigBee technology, Z-Wave technology, 6LoWPAN technology (i.e., IPv6 over Low Power Wireless Area Network (6LoWPAN)), ANT or ANT+ (Advanced Network Tools) technology, radio frequency (RF), Infrared Data Association (IrDA) compatible protocols, Local Area Networks (LAN), Wide Area Networks (WAN), Shared Wireless Access Protocol (SWAP), any combinations thereof, and other types of wireless networking protocols.

User interface <NUM> can include any pushbutton controls, video display, touchscreen display, and/or any other types of visual, audible, and/or tactile indicators.

Optics system <NUM> can include, for example, a laser or other light source in combination with one or more optical detectors (or light sensors).

Temperature control mechanism <NUM> can be any mechanism for maintaining test cartridge <NUM> at a desired temperature (e.g., about <NUM>) during use. Temperature control mechanism <NUM> can be, for example, a peltier cooler or resistive heater. A heater controller and various feedback mechanisms (e.g., negative temperature coefficient (NTC) thermistor, a thermocouple device, and the like) may be associated with temperature control mechanism <NUM>. Note further that the temperature control mechanism <NUM> may be included either within the PCM device <NUM> or within the test cartridge <NUM>.

Actuators <NUM> (e.g., actuators 118A, 118B) can be, for example, based on Piezo technology. In one example, actuators <NUM> are Piezo motors coupled to flexing ceramic actuators (see <FIG>, <FIG>, <FIG>) having, for example, a displacement to about <NUM>, fast response in the millisecond range, nanometer resolution, and a low operating voltage. In one example, actuators <NUM> are capable of delivering mechanical shear to the blood sample over a wide dynamic range of mechanical oscillations of from about <NUM> to about <NUM>. In certain other embodiments, actuators <NUM> may include voice coil motors, or any other motor suitable for use in PCM device <NUM>.

The presently claimed test cartridge is as defined in the claims, the presently claimed test cartridge comprises a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, the first and second members being linearly movable relative to each other, wherein the first and second members comprise a glass-filled thermoplastic polymer, wherein the glass-filled thermoplastic polymer members are optically transparent.

Test cartridge <NUM> includes two glass-filled thermoplastic polymer plates <NUM> (e.g., glass-filled thermoplastic polymer plates 122A, 122B) arranged substantially in parallel with each other and with a small gap therebetween for receiving a sample of blood to be tested. The surfaces of glass-filled thermoplastic polymer plates 122A, 122B face each other, and are spaced an amount sufficient to allow a relatively small sample of blood to contact the facing surfaces of glass-filled thermoplastic polymer plates 122A, 122B at the same time without an air space between.

In some embodiments, actuator 118A is mechanically coupled to glass-filled thermoplastic polymer plate 122A and actuator 118B is mechanically coupled to glass-filled thermoplastic polymer plate 122B. Using actuators 118A, 118B of PCM device <NUM>, glass-filled thermoplastic polymer plates 122A, 122B can be agitated to induce the platelet clotting process for measurement of blood thromboelastigraphy. Namely, using actuators 118A, 118B, glass-filled thermoplastic polymer plates 122A, 122B are movable relative to each other in a parallel and linear direction, and the spacing is such that the components of blood can initiate coagulation or adherence to each of the surfaces.

In test cartridge <NUM>, the small gap between glass-filled thermoplastic polymer plates 122A, 122B can be, for example, from about <NUM> to about <NUM>. Using actuators 118A, 118B of PCM device <NUM>, glass-filled thermoplastic polymer plates 122A, 122B slide past each other with controlled velocity to create a shear stress between the plates which is represented as T = µV/D where T equals shear stress, µ = viscosity, V = V1 + V2, wherein V is equal to the relative linear velocity of the plates, and D = gap between the plates.

Using optics system <NUM>, the coagulation response can be detected. Namely, optics system <NUM> may be used for detecting interaction of light with a blood sample located between glass-filled thermoplastic polymer plates 122A, 122B, with the interaction of light and detection thereof providing an indication of coagulation response of the blood sample. More specifically, with appropriate positioning of a light source and detectors (not shown), over time and in accordance with the variation of the movement of the glass-filled thermoplastic polymer plates 122A, 122B to generate a particular shear rate, information about both platelet response, fibrin response, and other responses of the blood components during coagulation can be obtained.

Using optics system <NUM>, optical detection may be done by transmitting light into the sample droplet, and detecting at least one of transmission, reflection and refraction of the light through the sample droplet at respective light detectors. Analog signals may be generated from the detection at the light detectors representative of coagulation properties of the blood in the sample droplet. Glass-filled thermoplastic polymer plates 122A, 122B are plates that are suitably transparent to allow light transmission of about <NUM>% or more of the incident light intensity. Namely, glass-filled thermoplastic polymer plates 122A, 122B are substantially optically transparent to allow optical signals to pass through the blood sample allowing direct optical visualization of a portion or all of the blood sample between the planar surfaces of glass-filled thermoplastic polymer plates 122A, 122B. This allows transmission, reflection, internal reflection, selective absorption, polarization or optical rotation, frustrated internal reflection (either partial or total), and conduction of laser beams or other light sources.

In optics system <NUM>, optical sensors are provided in position relative to glass-filled thermoplastic polymer plates 122A, 122B of test cartridge <NUM> for detecting light being projected from, for example, a laser or other light source (not shown), through and into a sample between glass-filled thermoplastic polymer plates 122A, 122B. The light can then be detected as light transmitted through the sample, reflected, refracted or otherwise modified in the path through the sample, and detected by optical sensors to obtain information about the coagulation properties of the blood sample.

More specifically, PCM device <NUM> and test cartridge <NUM> allow for the measurement of coagulation response based on the knowledge that the biophysical response of blood depends in part on the relative shear rate between the blood and surfaces with which it is in contact. More specifically, the higher the shear rate, the greater the platelet response so that the platelets then stick to the surfaces of the plates, and thereby trigger the fibrin polymerization and couple the motion of the two plates when only one is driven by the actuators (e.g., 118A, 118B). More specifically, it is recognized that in hemorrhaging events platelets need to react quickly so the use of a high shear rate for a short time period can allow accurate assessment of platelet response for these conditions. Thereafter, lower shear rates can be employed in terms of relative movements of the plates or members with respect to each other, to obtain an accurate assessment of fibrin response, or at an intermediate shear rate, both fibrin and platelet response.

"Shear" here is defined as the acceleration force felt by a particle in the moving bulk flow of fluid (blood) at the interface with the stationary solid (face of the glass plates). The shear "rate" is the differential of velocities felt on different aspects of the particle's cross-sectional area and is dependent on the particle's distance from the stationary surface.

Test cartridge <NUM> may further include a humidity control mechanism <NUM>. Humidity control mechanism <NUM> may be used to keep the inside of test cartridge <NUM> relatively moist, thereby slowing the drying time of the blood sample between glass-filled thermoplastic polymer plates 122A, 122B. In one example, humidity control mechanism <NUM> is one or more sponge-like pads that are placed inside test cartridge <NUM>, wherein the sponge-like pads are wetted, placed inside one or more sealed humidity pouches, and then installed in test cartridge <NUM>. A user may then optionally open the humidity pouches to slow drying of the blood sample. Examples of the sponge-like pads are shown hereinbelow with reference to <FIG>.

Test cartridge <NUM> may further include a disposable blood introduction device <NUM>. Disposable blood introduction device <NUM> is used to dose the correct amount of blood into test cartridge <NUM> using capillary action, without the need for a user to measure the blood. Disposable blood introduction device <NUM> may be used to fill test cartridge <NUM> with the correct amount of blood. Any extra blood in disposable blood introduction device <NUM> may then be safely disposed of together with disposable blood introduction device <NUM>. Disposable blood introduction device <NUM> typically includes a funnel or the like for introduction of the blood therein and a capillary at a flat bottom thereof that allows blood to move from disposable blood introduction device <NUM> into test cartridge <NUM>. More details of an example of test cartridge <NUM> are shown and described hereinbelow with reference to <FIG>, with specific details of disposable blood introduction device <NUM> shown in <FIG>, <FIG>, and <FIG>.

Referring now to <FIG>, various views are shown of an example of the presently disclosed test cartridge <NUM> having glass-filled thermoplastic polymer plates <NUM> for measurement of blood thromboelastography and having disposable blood introduction device <NUM>. Namely, <FIG> are perspective views of test cartridge <NUM> when fully assembled; <FIG> are perspective views and <FIG> are side views of test cartridge <NUM> with a portion of the housing removed and thereby revealing the internal components thereof; <FIG> are perspective views and <FIG> are side views of test cartridge <NUM> without the housing thereof; and <FIG> is an end view of test cartridge <NUM> when assembled.

Referring now to <FIG>, test cartridge <NUM> comprises a housing <NUM> for holding all the components thereof. In one example, housing <NUM> may be a two-piece housing, wherein the two pieces are snap-fitted or adhered together. Housing <NUM> can be formed, for example, of molded plastic. One end of housing <NUM> can have a grip-like shape, while the opposite end of housing <NUM> can have an opening <NUM> through which glass-filled thermoplastic polymer plates 122A, 122B can be engaged with actuators 118A, 118B of PCM device <NUM>, which are typically external to test cartridge <NUM>. Housing <NUM> may also have an optics window <NUM> in each side of housing <NUM>. The optics windows <NUM> substantially align with glass-filled thermoplastic polymer plates 122A, 122B and are used by optics system <NUM> of PCM device <NUM> for transmitting light in and out of test cartridge <NUM>.

<FIG> also show disposable blood introduction device <NUM> snap-fitted or press-fitted into housing <NUM> of test cartridge <NUM>. Disposable blood introduction device <NUM> may include a fluid channel <NUM> that is fluidly coupled to a fluid channel between glass-filled thermoplastic polymer plates 122A, 122B (see <FIG>). A cap <NUM> may also be provided for closing the opening that corresponds to disposable blood introduction device <NUM> when disposable blood introduction device <NUM> is not present in test cartridge <NUM>. Cap <NUM> can be, for example, pivotably coupled to housing <NUM>.

Referring now to <FIG>, test cartridge <NUM> may further include a pair of movable plate carriers <NUM> for holding glass-filled thermoplastic polymer plates <NUM>. For example, test cartridge <NUM> may include plate carrier 134A for holding glass-filled thermoplastic polymer plate 122A and plate carrier 134B for holding glass-filled thermoplastic polymer plate 122B. Each plate carrier <NUM> can be a flexible elongated member (e.g., a thermoplastic member). One end of the elongated member can be held stationary in housing <NUM> and the other end can include a frame for holding glass-filled thermoplastic polymer plate <NUM>, wherein the frame portion of each plate carrier <NUM> is substantially floating in midair. Accordingly, the frame portion of plate carrier <NUM> that is holding glass-filled thermoplastic polymer plate <NUM> may be movable. More particularly, the frame portion of plate carrier 134A may be movable in a parallel and linear direction with respect to the frame portion of plate carrier 134B.

Additionally, the frame portion of plate carrier <NUM> may include an engagement feature <NUM>. Namely, plate carrier 134A may include engagement feature 136A and plate carrier 134B may include engagement feature 136B (see <FIG>). Engagement features 136A, 136B are accessible through opening <NUM> of housing <NUM> and can be mechanically engaged with actuators 118A, 118B of PCM device <NUM>.

The frame portion of plate carrier <NUM> is typically shaped according to the shape of glass-filled thermoplastic polymer plate <NUM>. In one example, glass-filled thermoplastic polymer plate <NUM> is a circular disc. However, glass-filled thermoplastic polymer plate <NUM> and accordingly the frame portion of plate carrier <NUM> can be any shape, such as circular, ovular, square, rectangular, triangular, polygonal, and the like.

Referring still to <FIG>, test cartridge <NUM> may also include a pair of humidity pads <NUM> (e.g., humidity pads 146A, 146B). Humidity pads 146A, 146B are one example of humidity control mechanism <NUM> of test cartridge <NUM> as described in <FIG>. For example, humidity pads 146A, 146B may be sponge-like pads that are placed inside test cartridge <NUM>, wherein the sponge-like pads are wetted and then installed in test cartridge <NUM>. Humidity pads 146A, 146B are used to keep the inside of test cartridge <NUM> relatively moist and to slow the drying time of the blood sample between glass-filled thermoplastic polymer plates 122A, 122B. Test cartridge <NUM> is not limited to two humidity pads <NUM>. Test cartridge <NUM> can include any number of humidity pads <NUM>.

In some embodiments, each of the humidity pads <NUM> may be provided in a humidity pouch that is sealed, for example, using a foil seal for storage, but that can be peeled away when test cartridge <NUM> is ready for use. Accordingly, a pull tab <NUM> can be provided with each humidity pad <NUM> for pulling away the foil seal and exposing humidity pad <NUM>. In the exemplary embodiment shown in, e.g., <FIG>, humidity pad 146A has a pull tab 148A and humidity pad 146B has a pull tab 148B. <FIG>, and <FIG>, and <FIG> show test cartridge <NUM> with pull tabs148A, 148B removed and humidity pads 146A, 146B exposed.

With each test using test cartridge <NUM>, a certain disposable blood introduction device <NUM> may be installed and the blood sample introduced into the gap between glass-filled thermoplastic polymer plates 122A, 122B. Upon completing the blood introduction between glass-filled thermoplastic polymer plates 122A, 122B the disposable blood introduction device <NUM> may be removed and cap <NUM> secured. For example, <FIG> shows disposable blood introduction device <NUM> installed in test cartridge <NUM>, whereas <FIG> shows disposable blood introduction device <NUM> not installed in test cartridge <NUM> and cap <NUM> secured.

Further, <FIG> shows the process of fitting disposable blood introduction device <NUM> into a blood introduction channel <NUM> formed by the arrangement of plate carriers 134A, 134B. Namely, an outlet of disposable blood introduction device <NUM> may be press-fitted or snap-fitted into blood introduction channel <NUM>, then blood may flow from fluid channel <NUM> of disposable blood introduction device <NUM> into blood introduction channel <NUM>, and then into the gap between glass-filled thermoplastic polymer plates 122A, 122B.

Referring now to <FIG>, which is a perspective view of a pair of glass-filled thermoplastic polymer plates <NUM>, and <FIG> which is a perspective view of one glass-filled thermoplastic polymer plate <NUM>, each plate carrier <NUM> may include a flexing portion <NUM>. Plate carriers 134A, 134B are designed and positioned to hold the planar glass-filled thermoplastic polymer plates 122A, 122B substantially parallel and with a small gap in between for holding, for example, a blood sample <NUM>. Namely, the frame portion of plate carrier 134A is movable in a parallel and linear direction with respect to the frame portion of plate carrier 134B. The spacing of glass-filled thermoplastic polymer plates 122A, 122B in plate carriers 134A, 134B is such that the components of blood can initiate coagulation or adherence to each of the surfaces. For example, the small gap between glass-filled thermoplastic polymer plates 122A, 122B can be, for example, from about <NUM> to about <NUM>.

Further, the shape of engagement features <NUM> is designed to inhibit spreading when in use. Additionally, in one example, each glass-filled thermoplastic polymer plate <NUM> has a diameter d of about <NUM> (see <FIG>).

The glass constituent in glass-filled thermoplastic polymer plates <NUM> activates the platelets and induces blood clotting. The thermoplastic carrier (e.g., plate carriers <NUM>) allows the test cartridge <NUM> design to incorporate disposable blood introduction device <NUM>, allows custom-made shaping to maximize sensitivity and assay accuracy, minimizes the number of components in test cartridge <NUM>, minimizes costs, and allows for numerous mechanisms of platelet activation. There is no need for multiple components or the use of whole glass discs.

The polymers used in glass-filled thermoplastic polymer plates <NUM> can be a variety of polymers, such as nylon (polyamide), polycarbonate, polypropylene, polyethylene and polyester. Accordingly, in some embodiments, the glass-filled thermoplastic polymer is selected from the group consisting of nylon (polyamide), polycarbonate, polypropylene, polyethylene and polyester. In some embodiments, the amount of glass within the polymer can be between about <NUM>% to about <NUM>%. In other embodiments, the amount of glass within the polymer is about <NUM>%. Accordingly, in some embodiments, the glass-filled thermoplastic polymer contains glass beads and/or glass fibers and the amount of glass beads and/or glass fibers within the glass-filled thermoplastic polymer is between about <NUM>% to about <NUM>%. In other embodiments, the amount of glass beads and/or glass fibers within the glass-filled thermoplastic polymer is about <NUM>%.

In some embodiments, the glass in glass-filled thermoplastic polymer plates <NUM> can be found as fibers, beads, irregular pieces, or any form that activates the platelets in blood and induces blood clotting. In other embodiments, glass-filled thermoplastic polymer plates <NUM> are injection molded. In still other embodiments, glass-filled thermoplastic polymer plates <NUM> can be designed with intricate three-dimensional structures, such as thin channels, capillaries, undercuts and/or holes depending on the specific applications of the device.

In further embodiments, test cartridge <NUM> may further include at least one structure selected from the group consisting of a channel, a capillary, an undercut, and a hole. For example, a blood introduction system that includes a capillary or channel can be fully incorporated into the design of test cartridge <NUM>, allowing for test cartridge <NUM> to be used as a diagnostic test. In this example, the capillary plate and linkage arms are one single piece and therefore the capillary or channel is molded in one step. The inclusion of disposable blood introduction device <NUM> allows the blood of a subject to be added directly into test cartridge <NUM> without the need for external pipettes because the blood is delivered directly to the capillary/measurement area. Additionally, there is no need to measure or dose the blood because the correct amount of blood is delivered to the clot measurement area. In some embodiments, the glass-filled thermoplastic polymers can be used for the simultaneous introduction of blood samples and the measurement of clotting (including platelet activation and extrinsic pathways) in the measurement of blood thromboelastography. In other embodiments, the first glass-filled thermoplastic polymer plate 122A and second glass-filled thermoplastic polymer plate 122B of test cartridge <NUM> make up a blood sample collection cartridge which is removable from PCM device <NUM>. In still other instances of the disclosure, PCM device <NUM> further includes a memory device for storing data relating to a blood sample tested.

In some embodiments, the first and/or the second surface of the glass-filled thermoplastic polymer plates <NUM> have been treated to induce, slow, or modify the coagulation process for selecting in favor of or against specific aspects of coagulation of the sample. In other embodiments, treatment of the surfaces of the glass-filled thermoplastic polymer plates <NUM> enhances at least one characteristic selected from the group consisting of platelet or blood protein binding, reactivity, and activation. In yet other embodiments, the treatment of the surfaces reduces at least one characteristic selected from the group consisting of platelet or blood protein binding, reactivity, and activation. In further embodiments, test cartridge <NUM> is configured for analyzing blood rheology and coagulation of fresh whole blood or some fraction thereof without adding external reagents. In still other embodiments,
test cartridge <NUM> is configured for measuring with no functional delay the dynamic balance between pro- and anti-thrombotic hemostatic status by sequential samples from the same person or animal.

Referring now to <FIG> and to <FIG>, end views and top down views, respectively, are shown to illustrate more details of disposable blood introduction device <NUM> in relation to the pair of plate carriers <NUM> of the presently disclosed test cartridge <NUM>. Disposable blood introduction device <NUM> may include a grip portion <NUM> and a funnel portion <NUM> that includes fluid channel <NUM>. Further, disposable blood introduction device <NUM> may have an inlet <NUM> and an outlet <NUM>. As funnel portion <NUM> is tapered, the opening that is inlet <NUM> is larger than the opening that is outlet <NUM>. Additionally, a pair of alignment features <NUM> may be provided on funnel portion <NUM>. When installed, outlet <NUM> may be fitted into blood introduction channel <NUM> formed by plate carriers 134A, 134B and with alignment features <NUM> fitted against plate carriers 134A, 134B. <FIG>, <FIG>, and <FIG> show various detailed drawings of an example of disposable blood introduction device <NUM> of the presently disclosed test cartridge <NUM>. All exemplary dimensions shown in <FIG> and <FIG> are in millimeters (mm). In one example, the diameter of inlet <NUM> of disposable blood introduction device <NUM> is about <NUM>, the diameter of outlet <NUM> is about <NUM>, and the narrowest portion of fluid channel <NUM> has a diameter of about <NUM> (see <FIG>).

Accordingly, disposable blood introduction device <NUM> can provide a hollow tube of disposable material that includes, in some embodiments: a) an open top (e.g., inlet <NUM>); b) an upper cylindrical portion of funnel portion <NUM>; c) a frustoconical portion of funnel portion <NUM>; d) a lower cylindrical portion of funnel portion <NUM>; d) a flat bottom at outlet <NUM>; and e) a lip (e.g., grip portion <NUM>) attached to the upper cylindrical portion and/or to the frustoconical portion. Further, the wall thickness of funnel portion <NUM> gradually tapers from inlet <NUM> to outlet <NUM>. Additionally, disposable blood introduction device <NUM> can include a solid plug cap (not shown), which is attached to, for example, grip portion <NUM>; wherein the solid plug cap sealingly nests within inlet <NUM>.

Disposable blood introduction device <NUM> can be formed, for example, of any kind of polymer or glass material that can hold blood and allows the blood at the bottom of the device to move into test cartridge <NUM> when installed. Disposable material can be sterilized before use. Examples of materials include nylon (polyamide), polycarbonate, polypropylene, polyethylene, polyester, and the like.

In operation, blood is introduced to disposable blood introduction device <NUM> through inlet <NUM>. Funnel portion <NUM> and the fluid channel <NUM> therein go from a larger diameter at the inlet <NUM> of disposable blood introduction device <NUM> to a smaller diameter near the outlet <NUM> of disposable blood introduction device <NUM>. The smaller diameter at the outlet <NUM> of disposable blood introduction device <NUM> allows a small amount of blood to move out of disposable blood introduction device <NUM> at a time and into test cartridge <NUM>, when installed, in a measured manner. Once the blood intake area of test cartridge <NUM> is full, blood no longer moves from disposable blood introduction device <NUM> into test cartridge <NUM>. Accordingly, disposable blood introduction device <NUM> allows the blood to automatically dose into test cartridge <NUM>. In some embodiments, the smaller diameter near the outlet <NUM> of disposable blood introduction device <NUM> is small enough so that blood does not move from disposable blood introduction device <NUM> unless disposable blood introduction device <NUM> is contacted with the blood intake area of test cartridge <NUM> (i.e., through capillary action).

For purposes of this disclosure, it should be noted that by "blood" is meant a mixture of whole blood with one or more substances, a fraction of whole blood containing one or more of the constituents of whole blood, a fraction of whole blood mixed with one or more non blood substances, or a purified blood constituent, such as blood platelets or serum, a reconstituted blood preparation, a modified blood sample, or a blood substitute.

Blood can be added to disposable blood introduction device <NUM> using a pipette tip or a syringe. However, in some instances of the disclosure, the blood is added to disposable blood introduction device <NUM> directly from the body of a subject, such as by using a capillary blood collection (finger prick) method. The finger can be punctured by using any of a variety of puncture or incision devices. In other embodiments, the blood is added to disposable blood introduction device <NUM> from a storage container, such as from a tube, bottle, and the like, by using an alternative means, such as by using a pipette tip, for example. This may be necessary if the blood is stored before being tested, such as after a venous blood draw, for example. Excess or unused blood is removed by detaching disposable blood introduction device <NUM> from the test cartridge.

Disposable blood introduction device <NUM> minimizes excess blood, allows blood to be added without measurement/pipetting and allows removal of excess blood, thereby reducing contamination risk from the unused blood. Therefore, disposable blood introduction device <NUM> can be used in point-of-care settings, such as in the field, operating room, or in emergency situations.

Referring now to <FIG>, a side view is shown of an example of a glass-filled thermoplastic polymer rotation mechanism <NUM> that can be used in place of the glass-filled thermoplastic polymer plates <NUM> in the presently disclosed PCM device <NUM> and/or test cartridge <NUM>. In this example, glass-filled thermoplastic polymer rotation mechanism <NUM> comprises a housing <NUM> with a central bore <NUM> (e.g., a tapered central bore) and an inner rod <NUM>. Housing <NUM> is a glass-filled thermoplastic polymer housing and inner rod <NUM> is a glass-filled thermoplastic polymer rod.

Inner rod <NUM> can be rotated relative to central bore <NUM> in housing <NUM>. In this instance of the disclosure, at least one member of the device is a rod (e.g., inner rod <NUM>) that can rotate to initiate coagulation. In this case, glass-filled thermoplastic polymer rotation mechanism <NUM> can be used for a simple two component test in which blood (e.g., blood sample <NUM>) is sandwiched between housing <NUM> and inner rod <NUM>. Namely, a drop of blood is provided at the inlet of central bore <NUM>, then the blood flows by capillary action between housing <NUM> and inner rod <NUM>.

The glass-filled thermoplastic polymer inner rod <NUM> and the glass-filled thermoplastic polymer housing <NUM> rotate relative to each other creating a shear force on the blood and, coupled with the glass activation, allow a clot to be measured by a load cell, electrical resistance, and/or torque measurements. In one example, inner rod <NUM> and housing <NUM> have a clearance of from about <NUM> to about <NUM>. In other embodiments, glass-filled thermoplastic polymer rotation mechanism <NUM> further comprises a third member having a third surface spaced an amount sufficient to allow a sample droplet of blood to contact the surface of inner rod <NUM> and initiate coagulation.

Referring now to <FIG> and <FIG>, a perspective view and a plan view, respectively, are shown of one example of the physical instantiation of PCM device <NUM> when holding test cartridge <NUM>. Additionally, <FIG> shows a close-up view of a portion of the exemplary PCM device <NUM> shown in <FIG> and <FIG>. In this example, PCM device <NUM> comprises a base plate <NUM> that has multiple through-holes <NUM>. The multiple through-holes <NUM> can be used, for example, to attach a cover (not shown) or any other mechanisms to base plate <NUM>. Base plate <NUM> can be formed, for example, of molded plastic or aluminum.

In some instances of the disclosure, a pair of alignment blocks <NUM> are mounted on base plate <NUM> between which housing <NUM> of test cartridge <NUM> can be snuggly fitted. A guide rail mounting bracket <NUM> that supports a pair of floating linear guide rails <NUM> that are coupled to a pair of receptacles <NUM> may also be mounted on base plate <NUM>, wherein the pair of receptacles <NUM> are designed to physically couple to engagement features 136A, 136B of plate carriers 134A, 134B of test cartridge <NUM> (see <FIG>). More details of receptacles <NUM> and engagement features <NUM> are shown and described hereinbelow with reference to <FIG>.

Actuators <NUM> (e.g., Piezo actuators) may also be mounted on base plate <NUM> and may be mechanically coupled to receptacles <NUM> via the floating linear guide rails <NUM>. Further, a pair of proximity sensors <NUM> (e.g., induction proximity sensors) may be mounted on base plate <NUM>. Proximity sensors <NUM> may be used to sense the positions of the floating linear guide rails <NUM>. Further, an electronics housing <NUM> may be mounted on base plate <NUM>. Electronics housing <NUM> contains any control electronics associated with PCM device <NUM>, such as any of the electronics described hereinabove with reference to <FIG>.

Referring now to <FIG>, a perspective view is shown of a portion of PCM device <NUM> shown in <FIG> and <FIG>, but absent test cartridge <NUM>. Namely, <FIG> shows a cavity <NUM> that may be formed in base plate <NUM>. The footprint of cavity <NUM> is substantially the same as the shape of housing <NUM> of test cartridge <NUM>, whereas test cartridge <NUM> rests in cavity <NUM> when installed in PCM device <NUM>.

Referring now to <FIG>, an example is shown of the actuator engagement mechanisms of PCM device <NUM> shown in <FIG> and <FIG>. Namely, <FIG> shows a plan view of an example of one of the receptacles <NUM>. In this example, receptacle <NUM> has a horseshoe type of shape. Two pinch contact ribs <NUM> are provided on the two "fingers," respectively, of receptacle <NUM>. Pinch contact ribs <NUM> ensure reliable engagement with engagement features <NUM> of plate carriers <NUM> of test cartridge <NUM>. To further ensure reliable engagement, engagement feature <NUM> of plate carriers <NUM> of test cartridge <NUM> may also include a ridge <NUM>, which provides a point contact with receptacle <NUM>.

Referring now to <FIG>, a perspective view is shown of another example of a test cartridge <NUM> that includes glass-filled thermoplastic polymer plates <NUM>.

Referring now to <FIG>, a perspective view is shown of an example of a dual channel PCM device <NUM> for receiving and holding two test cartridges <NUM>. Namely, dual channel PCM device <NUM> provides the capability to receive two test cartridges <NUM> and includes the hardware necessary to run two tests simultaneously.

In some instances of the disclosure, dual charnel PCM device <NUM> includes a housing or assembly <NUM> that is designed to receive and process two test cartridges <NUM>. Namely, housing <NUM> has a first opening <NUM> for receiving the first test cartridge 120A and a second opening <NUM> for receiving the second test cartridge 120B. Dual channel PCM device <NUM> includes substantially the same components and functionality that is described hereinabove with reference to <FIG> and <FIG> through <FIG>, except duplicate components and/or hardware are included in order to support two test cartridges <NUM> simultaneously. Accordingly, dual channel PCM device <NUM> has a first channel (i.e., channel one) and a second channel (i.e., channel two).

Using dual channel PCM device <NUM>, two tests can be run simultaneously. For example, dual channel PCM device <NUM> allows one of two scenarios: (<NUM>) a time delayed thrombelastogram relative to a first test (i.e., to make a comparison to evaluate effectiveness of treatment, etc.) or (<NUM>) two distinct tests (e.g., thrombelastogram and fibrinogen test, or heparin, other platelet function, etc.). Note that the dual tests may be run simultaneously, at different times, or at overlapping times (i.e. the second test is begun while the first test is running).

Using the single channel PCM device <NUM> and/or dual channel PCM device <NUM>, a number of different test cartridges <NUM> with added "chemistry" for fibrinogen testing (or heparin and other platelet function tests as extras) would allow the emergency trauma, cardiology, and vascular clinicians a full suite of clinical diagnostics relevant to their requirements. One advantage is to be able to run either standard whole venous blood, a parallel fibrinogen test, or a second time delayed standard to monitor therapeutic change/response.

The ability to run a second test cartridge within the same PCM device (e.g., dual channel PCM device <NUM>), either with, or without "chemistry," would leverage all the current technology and also provide additional clinical information. However, this could be more flexible than current technology, and also allow near patient clinical responsiveness to additional diagnostic requirements or to monitor therapeutic response. This would be useful as it would take the functionality and versatility of current devices but truly make it point of care as it would be accessible without the pipetting steps.

Running a second standard sample within the same PCM device adds the ability to see a new curve on the same patient, run either after a therapeutic change - i.e., plasma administration, or a significant change in clinical condition alongside the first trace for direct comparison without stopping the first test or requiring a second PCM device.

Using, for example, dual channel PCM device <NUM>, the time delayed traces can be displayed on the same screen at the same time. Channel two could also be used to run a cartridge with "chemistry" as previously discussed. The key opportunities for the additional chemistry include:.

"Bog standard" platelet function analyzers aim to work in a similar way, but some analyzers use chemistry to test specific platelet activation receptor function (ADP, Cyclo ox), which can determine whether aspirin or clopidogrel are actually working. This could also be incorporated within the presently disclosed PCM devices, so long as additional "chemistry" is introduced.

In addition to coagulation tests, non-clotting tests may also be performed. For example, with respect to hemoglobin, the addition of a near patient hemoglobin assay to a thrombelastogram would be very useful to the clinician, as it is currently also requested. It is possible to introduce an optical test through the glass-filled thermoplastic polymer plates <NUM> on the same sample, which would reduce time lag or the reliance on another near patient test. Further, incorporating a separate assay into the same device would therefore be beneficial.

With respect to blood glucose, blood glucose is often tested in hemorrhage situations, and although the technology is widespread, a combined glucose oxidase electrochemical sensor could provide the information more simply than current practices. Current practice is to either use a separate monitor using capillary blood or measure glucose as part of an arterial blood gas analysis (which, in practice, is not ideal).

With respect to arterial blood gas analysis, arterial blood gas analyzers have moved out of the lab and into the critical care areas over the last <NUM>-<NUM> years. There is an added advantage to the presently disclosed PCM devices in that repeated samples are essentially looked at during major cases in a similar way to repeat clotting.

The presently disclosed PCM Device <NUM> or <NUM> may also be used to conduct Hb and platelet count tests. Using, for example, dual channel PCM device <NUM>, Hb and platelet count tests can be performed in situ using glass-filled thermoplastic polymer plates <NUM>. Advantages include: (<NUM>) an optical check can be performed on the exact sample for coagulation, (<NUM>) it eliminates variation between blood draw/fingerstick-venous-arterial/non-pipetting, (<NUM>) it eliminates the need for additional tests (e.g., lab tests or hemo-cue), (<NUM>) anemia/vascular packers, and (<NUM>) platelet count test (also using optical plates <NUM>).

The presently claimed method is as defined in the claims. Referring now to <FIG>, a flow diagram is presented of an example of a method <NUM> of measuring coagulation response in a blood sample using, for example, PCM device <NUM> and test cartridge <NUM>. Method <NUM> includes the following steps.

At a step <NUM>, a sample droplet of blood is placed between and in contact with the first and second facing surfaces of oppositely disposed glass-filled thermoplastic polymer plates <NUM> of test cartridge <NUM>. In one example, disposable blood introduction device <NUM> is used to place the blood sample between glass-filled thermoplastic polymer plates 122A and 122B.

At a step <NUM>, at least one glass-filled thermoplastic polymer plate <NUM> is moved linearly with respect to the other glass-filled thermoplastic polymer plate <NUM> at a predetermined speed sufficient to activate platelets through exposure to shear forces. In one example, actuator 118A of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122A linearly with respect to glass-filled thermoplastic polymer plate 122B at a predetermined speed sufficient to activate platelets through exposure to shear forces. In another example, actuator 118B of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122B linearly with respect to glass-filled thermoplastic polymer plate 122A at a predetermined speed sufficient to activate platelets through exposure to shear forces. In yet another example, actuators 118A and 118B of PCM device <NUM> are used to move both glass-filled thermoplastic polymer plates 122A and 122B linearly with respect to each other at a predetermined speed sufficient to activate platelets through exposure to shear forces.

At a step <NUM>, using, for example, optics system <NUM> of PCM device <NUM>, an optical detection operation is performed (i.e., via measurement of mechanical displacement) of the interaction between the surfaces of glass-filled thermoplastic polymer plates 122A, 122B, resulting from changes in the viscosity of the sample fluid and binding to the surfaces in order to measure coagulation response of the droplet of blood.

Referring now to <FIG>, a flow diagram is presented of a method <NUM>, which is another example of a method of measuring coagulation response in a blood sample using, for example, PCM device <NUM> and test cartridge <NUM>. Method <NUM> may include, but is not limited to, the following steps.

At a step <NUM>, a sample droplet of blood is placed between and in contact with the first and second facing surfaces of the oppositely disposed glass-filled thermoplastic polymer plates <NUM> of test cartridge <NUM>. In one example, disposable blood introduction device <NUM> is used to place the blood sample between glass-filled thermoplastic polymer plates 122A and 122B.

At a step <NUM>, at least one glass-filled thermoplastic polymer plate <NUM> is moved linearly with respect to the other glass-filled thermoplastic polymer plate <NUM> at a first speed. In one example, actuator 118A of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122A linearly with respect to glass-filled thermoplastic polymer plate 122B at a first speed. In another example, actuator 118B of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122B linearly with respect to glass-filled thermoplastic polymer plate 122A at a first speed. In yet another example, actuators 118A and 118B of PCM device <NUM> are used to move both glass-filled thermoplastic polymer plates 122A and 122B linearly with respect to each other at a first speed.

At a step <NUM>, using, for example, optics system <NUM> of PCM device <NUM>, a first coagulation response of the blood indicative of platelet response in the blood is optically detected.

At a step <NUM>, at least one glass-filled thermoplastic polymer plate <NUM> is moved linearly with respect to the other glass-filled thermoplastic polymer plate <NUM> at a second speed. In one example, actuator 118A of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122A linearly with respect to glass-filled thermoplastic polymer plate 122B at a second speed. In another example, actuator 118B of PCM device <NUM> is used to move glass-filled thermoplastic polymer plate 122B linearly with respect to glass-filled thermoplastic polymer plate 122A at a second speed. In yet another example, actuators 118A and 118B of PCM device <NUM> are used to move both glass-filled thermoplastic polymer plates 122A and 122B linearly with respect to each other at a second speed.

At a step <NUM>, using, for example, optics system <NUM> of PCM device <NUM>, a second coagulation response of the blood indicative of fibrin polymerization is optically detected.

In method <NUM> of <FIG> and/or method <NUM> of <FIG>, to detect two different types of coagulation response, glass-filled thermoplastic polymer plates <NUM> can be moved relative to each other at a first speed and a response optically detected, and thereafter moved at a second speed which is slower than the first speed and a second response optically detected, typically fibrin polymerization. In addition, in the case where only one glass-filled thermoplastic polymer plate <NUM> is moved, it should be appreciated that the visco elastic response of the blood sample on the surfaces of both glass-filled thermoplastic polymer plates <NUM> can cause the movement of the first glass-filled thermoplastic polymer plate <NUM> to induce movement of the second glass-filled thermoplastic polymer plate <NUM> ("coupled motion"), which can be measured as indicative of visco elastic response of the blood, ultimately leading to conclusions which may be inferred relative to coagulation response. Moreover, by moving glass-filled thermoplastic polymer plates <NUM> at different speeds over time, changes in the visco elastic state of the blood sample may be measured as a clot is formed, which is also indicative of coagulation response.

In some embodiments, method <NUM> of <FIG> and/or method <NUM> of <FIG> include moving one glass-filled thermoplastic polymer plate <NUM> relative to the other glass-filled thermoplastic polymer plate <NUM> in a manner causing the other glass-filled thermoplastic polymer plate <NUM> to move because of visco elastic coupling between the blood and the other glass-filled thermoplastic polymer plate <NUM>; and determining the visco elastic properties of the blood from the movement of the other glass-filled thermoplastic polymer plate <NUM>. In other embodiments, the method further includes detecting strain rates caused by movement of the one glass-filled thermoplastic polymer plate <NUM> and the other glass-filled thermoplastic polymer plate <NUM> caused by visco elastic coupling between the one glass-filled thermoplastic polymer plate <NUM> and the other glass-filled thermoplastic polymer plate <NUM> caused by the blood sample; and determining the coagulation state of the blood by inference analysis based on visco elasticity of the blood sample determined from mechanical coupling between the two glass-filled thermoplastic polymer plates <NUM> and the resulting strain rates. In still other embodiments, method <NUM> of <FIG> and/or method <NUM> of <FIG> further include continually measuring the visco elasticity of the blood over time to monitor changes over time of the coagulation response of the blood. In some instances of the disclosure, the sample droplet of blood comes directly from the body of a subject.

In other embodiments, test cartridge <NUM> can be used in measurement of the viscosity of a multitude of fluids other than blood, including non-biological fluids. For example, using devices and methods similar to those taught herein, the viscosity of any number of other fluids, including non-biological fluids, can be measured for significantly less than current measurement methods.

Referring now to <FIG> is a flow diagram of an example of a method <NUM> of introducing blood into a test cartridge (e.g., test cartridge <NUM>) using the presently disclosed disposable blood introduction device <NUM>. Method <NUM> may include, but is not limited to, the following steps.

At a step <NUM>, the disposable blood introduction device <NUM> of the present invention is inserted into test cartridge <NUM>. For example, the outlet end <NUM> of disposable blood introduction device <NUM> is inserted into blood introduction channel <NUM> formed by the arrangement of plate carriers 134A, 134B in test cartridge <NUM>.

At a step <NUM>, a droplet of blood is inserted into inlet <NUM> of disposable blood introduction device <NUM> and then the blood flows into fluid channel <NUM> of disposable blood introduction device <NUM> by capillary action.

At a step <NUM>, the blood is allowed to move from disposable blood introduction device <NUM> into test cartridge <NUM> until the blood stops moving. Namely, by capillary action blood flows from disposable blood introduction device <NUM> into the gap between glass-filled thermoplastic polymer plates 122A, 122B of test cartridge <NUM>. When the gap between glass-filled thermoplastic polymer plates 122A, 122B is filled with blood, the blood flow from disposable blood introduction device <NUM> automatically stops.

At a step <NUM>, disposable blood introduction device <NUM> is removed from test cartridge <NUM> after the blood has stopped moving into test cartridge <NUM>.

Following long-standing patent law convention, the terms "a," "an," and "the" refer to "one or more" when used in this application, including the claims. Thus, for example, reference to "a subject" includes a plurality of subjects, unless the context clearly is to the contrary (e.g., a plurality of subjects), and so forth.

Throughout this specification and the claims, the terms "comprise," "comprises," and "comprising" are used in a non-exclusive sense, except where the context requires otherwise. Likewise, the term "include" and its grammatical variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.

For the purposes of this specification and appended claims, unless otherwise indicated, all numbers expressing amounts, sizes, dimensions, proportions, shapes, formulations, parameters, percentages, parameters, quantities, characteristics, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term "about" even though the term "about" may not expressly appear with the value, amount or range. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are not and need not be exact, but may be approximate and/or larger or smaller as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art depending on the desired properties sought to be obtained by the presently disclosed subject matter. For example, the term "about," when referring to a value can be meant to encompass variations of, in some embodiments, ± <NUM>% in some embodiments ± <NUM>%, in some embodiments ± <NUM>%, in some embodiments ± <NUM>%, in some embodiments ± <NUM>%, in some embodiments ±<NUM>%, in some embodiments ± <NUM>%, and in some embodiments ± <NUM>% from the specified amount, as such variations are appropriate to perform the disclosed methods or employ the disclosed compositions.

Claim 1:
A method of measuring coagulation response in a blood sample, comprising the steps of:
a. placing a sample droplet of blood between and in contact with a first surface and a second surface of oppositely disposed glass-filled thermoplastic polymer members (122A, 122B), wherein the glass-filled thermoplastic polymer members are optically transparent;
b. moving at least one member (122A, 122B) linearly with respect to the other member (122A, 122B) at a predetermined speed sufficient to activate platelets through exposure to shear forces; and
c. optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the member (122A, 122B) surfaces in order to measure coagulation response of the droplet of blood.