Abstract:
Disclosed is a point of care diagnostic system that includes an analytic cartridge adapted to receive a blood draw tube such that the cartridge can directly accept a blood sample from the blood draw tube. The cartridge is adapted to perform an assay on the blood sample and to produce an indication of an assay result entirely within the cartridge.

Description:
REFERENCE TO PRIORITY DOCUMENTS  
       [0001]     This application is a continuation of co-pending U.S. patent application Ser. No.10/746,127, filed Dec. 23, 2003, which claims priority of U.S. Provisional Patent Application Ser. No. 60/470,725, filed May 14, 2003. Priority of the aforementioned filing dates is hereby claimed, and the disclosures of the aforementioned patent applications are hereby incorporated by reference.  
       BACKGROUND OF THE INVENTION  
       [0002]     1. Field of the Invention  
         [0003]     The present invention relates generally to a point of care diagnostic system that has a plurality of modules and associated cartridges, and more particularly, to a point of care diagnostic system that includes a plurality of modules that share common QC protocols.  
         [0004]     2. Description of the Related Art  
         [0005]     Blood and other body fluid tests are important diagnostic methods in patient care and treatment. The reliability and the accuracy of the tests are critical in correctly diagnosing the patient and administrating proper treatment. The Food and Drug Administration (FDA) has established numerous quality standards for the various blood or body fluid tests. Monitoring the test process is beneficial in producing reliable and accurate test results.  
         [0006]     One way of monitoring the test process is periodically performing the monitoring test on standard test samples. The monitoring test results are compared with expected results to verify the accuracy of the test processes or correct the test instrument or process when appropriate. In this approach, the test processes are assumed to generate consistent result between the monitoring tests.  
         [0007]     Another way of monitoring the test process is including standard test samples in the test process. This approach is suitable for a test process that performs tests on multiple samples. The test results on the standard test samples are compared with expected results to verify the accuracy of the test processes. In this approach, the test processes on real samples are assumed to generate result consistent with those on standard test samples.  
         [0008]     These monitoring processes are time and cost inefficient. They are deficient in meeting the needs of point of care, e.g., hospital emergency room/department, test processes. In addition to being reliable and accurate, an emergency room test process should be simple to operate and generate diversity of analytical results fast.  
         [0009]     Accordingly, there is a need for a point of care diagnostic platform that has a plurality of modules coupled to common host computer. There is another need for a point of care diagnostic platform with a plurality of modules that share common QC protocols. Yet there is another need for a point of care diagnostic platform with a plurality of modules coupled to a host computer and an external communication system. There is still another need for a point of care diagnostic platform with a plurality of modules, and a plurality of analytic cartridges, where each cartridge is associated with a module and is configured to directly accept a blood sample from a standard blood draw tube. Yet there is a further need for a point of care diagnostic platform that has a plurality of modules, a host computer coupled to the modules, a common external communication interface, with each module sharing the common external communication interface.  
       SUMMARY OF THE INVENTION  
       [0010]     Accordingly, an object of the present invention is to provide a point of care diagnostic platform that includes a plurality of modules that share common QC protocols.  
         [0011]     Another object of the present invention is to provide a point of care diagnostic platform with a plurality of module coupled to a common host computer.  
         [0012]     Yet another object of the present invention is to provide a point of care diagnostic platform with a plurality of modules, a host computer coupled to the plurality of modules and an external communication system.  
         [0013]     Still another object of the present invention is to provide a point of care diagnostic platform with a plurality of modules, and a plurality of analytic cartridges, where each cartridge is associated with a module of the plurality of modules and is configured to directly accept a blood sample from a standard blood draw tube.  
         [0014]     Another object of the present invention is to provide a point of care diagnostic platform with a plurality of modules; a host computer coupled to the plurality of modules and a common external communication interface, with each module sharing the common external communication interface.  
         [0015]     A further object of the present invention is to provide a point of care diagnostic platform with a plurality of modules coupled to a common external communication interface such as a least one of WAN or a LAN.  
         [0016]     Another object of the present invention is to provide a point of care diagnostic platform with a plurality of modules coupled to a common external communication interface that is coupled to a wireless network.  
         [0017]     A further object of the present invention is to provide a point of care diagnostic platform with a plurality of modules coupled to a hospital information network or a laboratory information network.  
         [0018]     Yet another object of the present invention is to provide a point of care diagnostic platform with a plurality of modules and a plurality of analytic cartridges that are each bar-coded with information for test protocols, and lot expiration dates.  
         [0019]     Still a further object of the present invention is to provide a point of care diagnostic platform with a plurality of modules and a plurality of analytic cartridges that retain and seal fluids.  
         [0020]     Yet another object of the present invention is to provide a point of care diagnostic platform that has a plurality of modules and a plurality of analytic cartridges, where all fluids in a cartridge, including a patient sample, remain within the cartridge.  
         [0021]     These and other objects of the present invention are achieved in a point of care diagnostic platform includes a plurality of modules. A plurality of analytic cartridges are provided. Each cartridge is associated with a module and is configured to directly accept a blood sample from a standard blood draw tube.  
         [0022]     In another embodiment of the present invention, a point of care diagnostic platform includes a plurality of modules. A host computer is coupled to the plurality of modules and a common external communication interface. Each module shares the common external communication interface.  
         [0023]     In another embodiment of the present invention, a point of care diagnostic platform includes a plurality of modules each sharing the same QC protocols. A plurality of analytic cartridges are included. A host computer is coupled to the plurality of modules. The host computer is coupled to an interface. Each module has a corresponding interface component.  
         [0024]     In another embodiment of the present invention, a point of care diagnostic platform includes a plurality of modules. A plurality of analytic cartridges are provided that each are bar-coded with information for test protocols, and lot expiration dates.  
         [0025]     In another embodiment of the present invention, a point of care diagnostic platform includes a plurality of modules. A plurality of analytic cartridges are provided that retain and seal fluids.  
         [0026]     In another embodiment of the present invention, a point of care diagnostic platform includes a plurality of modules. A plurality of analytic cartridges are provided. All fluids in the cartridges, including patient samples, remain within the cartridges.  
         [0027]     In another embodiment of the present invention, a point of care diagnostic platform is provided that includes a plurality of modules. A plurality of analytic cartridges are provided. Each cartridge has wet and dry chemistries and at least one substrate that carriers a chemistry.  
         [0028]     In one aspect, there is disclosed a point of care diagnostic system that includes an analytic cartridge adapted to receive a blood draw tube such that the cartridge can directly accept a blood sample from the blood draw tube. The cartridge is adapted to perform an assay on the blood sample and to produce an indication of an assay result entirely within the cartridge. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0029]      FIG. 1 ( a ) is a block diagram illustrating one embodiment of a point of care diagnostic platform of the present invention, with a user interface, host computer, multiple single-cartridge test processing modules and an external communication system.  
         [0030]      FIG. 1 ( b ) is a block diagram illustrating another embodiment of a point of care diagnostic platform of the present invention, with multiple multi-cartridge test processing modules.  
         [0031]      FIG. 1 ( c ) is a block diagram illustrating another embodiment of a point of care diagnostic platform of the present invention, with the host computer being integrated with multiple, multi-cartridge modules.  
         [0032]      FIG. 1 ( d ) is a block diagram illustrating another embodiment of a point of care diagnostic platform of the present invention, with the host computer and user interface both integrated with multiple, multi-cartridge modules.  
         [0033]      FIG. 1 ( e ) is a block diagram illustrating another embodiment of a point of care diagnostic platform of the present invention, with the host computer and user interface integrated with multiple, single-cartridge modules.  
         [0034]      FIG. 2  is a cross-sectional view of one embodiment of a cartridge that can be utilized with the point of care diagnostic platform of the present invention.  
         [0035]      FIG. 3  is a cross-sectional view of a sample tube that can be utilized with cartridges of the present invention.  
         [0036]      FIG. 4  is a schematic diagram illustrating one embodiment of the docking, and the relationship between a cartridge and a module of the present invention.  
         [0037]      FIG. 5  is a schematic diagram illustrating another embodiment of the docking, and the relationship between a cartridge and a module of the present invention.  
         [0038]      FIG. 6  is a schematic diagram illustrating another embodiment of the docking, and the relationship between a cartridge and a module of the present invention.  
         [0039]      FIG. 7  is a cross-sectional view of one embodiment of a cartridge utilized with the present invention, illustrating air, sample and reagent flow channels.  
         [0040]      FIG. 8  is a flow chart illustrating an overall methodology of the point of care diagnostic platform of the present invention.  
         [0041]      FIG. 9  is a flow chart illustrating one embodiment of a cartridge processing procedure implemented with the point of care diagnostic platform of the present invention.  
         [0042]      FIG. 10  is a flow chart illustrating one embodiment of an immunoassay operating procedure implemented with the point of care diagnostic platform of the present invention.  
         [0043]      FIG. 11  is a flow chart illustrating one embodiment of a hematology operating procedure implemented with the point of care diagnostic platform of the present invention. 
     
    
     DETAILED DESCRIPTION  
       [0044]     As illustrated in  FIG. 1 ( a ), one embodiment of the present invention is a point of care diagnostic platform, denoted generally as  10 , and its method of use. Point of care diagnostic platform  10  includes a plurality of modules  12 . A variety of different modules can be included but not limited to, immunoassay, hematology, electrolyte, molecular diagnostic, coagulation, blood gas, chemistry and the like. The modules  12  can share at least a portion of a common functionality of operation such as fluid movement, sample introduction, and the like. In one embodiment, each module  12  contains common functionalities, and unique technologies that correspond to one or more selected chemistries. In the  FIG. 1 ( a ) embodiment, modules  12  are multiple single-cartridge test processing modules.  
         [0045]     Platform  10  can deliver a multitude of discreet testing capabilities in a standardized manner. Modules  12  can have common operation platforms. Examples of common operation systems are user interface, quality control, calibration, training, connection to various laboratory information systems, hospital information systems, emergency room information systems, wireless communication and the like.  
         [0046]     A host computer  14  is coupled to the plurality of modules  12  and also to a user interface  16 . Each module  12  is coupled to the user interface  16 . Host computer  14  has a variety of different capabilities, including but not limited to user interface, quality control, calibration, training, connection to various laboratory information systems, hospital information systems, emergency room information systems, wireless communication and the like. User interface  16  is coupled to each module  12  User interface  16  provides uniform (automated and standardized) connectivity to the plurality of modules  12  as well as communication to other hospital and laboratory information systems. It will be appreciated that standardized includes industry standards as documented by the Connectivity Industry Consortium. User interface  16  establishes a database of analyzed samples and provides the operator with quality control options for the plurality of modules  12 . This is achieved by centralizing and tracking the collective output of the plurality of modules  12 . In one embodiment, user interface  16  includes capability for at least one of a cardiac, fertility, kidney, coagulation, electrolyte and hematology panel, molecular diagnostics and chemistry panels, and the like.  
         [0047]     Each module  12  has a corresponding interface component for module control and sample results acquisition. In one embodiment, host computer  14  is also coupled to an external communication system  18 . A variety of different external communication systems are suitable including but not limited to a, WAN, LAN, wireless network, hospital information network, laboratory information network, and the like. Platform  10  can be connected directly or indirectly to a emergency room/department patient management network  
         [0048]     In one embodiment, each module  12  shares common QC protocols. The QC protocols include but are not limited to the following, module electronic verification, real-time process monitoring, patient record-keeping, periodic liquid control results monitoring, and the like. The QC protocols are initiated in the same manner regardless of the module  12  that is tested. Electronic monitoring of the process at each module  12  is continuous and transparent to the operator and do not require operator attention. Results are stored in module specific databases. Each module can utilize specific electronic and/or optical parameter monitoring. Changes in the electronic and optical parameters are tracked during the operation of the module  12  involved, and the outputs compared to expected thresholds/changes. These changes are indicative of correct internal operation during sample processing.  
         [0049]     In another embodiment, illustrated in  FIG. 1 ( b ), multiple, multi-modules are provided, where a module  12  can be utilized with more than one cartridge. In  FIG. 1 ( c ) host computer  14  is integrated with multiple, multi-cartridge modules  12 . In the  FIG. 1 ( d ) embodiment, host computer  14  and user interface  16  are both integrated with multiple, multi-cartridge modules  12 . In the  FIG. 1 ( e ) embodiment, host computer and user interface  16  are integrated with multiple, single-cartridge test processing modules  12 .  
         [0050]     Point of care diagnostic platform  10  includes a plurality of cartridges  20 , illustrated in  FIG. 2 . Cartridges  20  include but are not limited to cardiac, fertility, kidney, coagulation, electrolyte and hematology panel, molecular diagnostics and chemistry panels, and the like.  
         [0051]     Each cartridge  20  can include a dock  22  for receiving a sample tube, an air dock  24  that can be engaged by a module  12 , a rotary valve  26 , which can also be engaged by a module  12 , a calibration chamber  28 , waste chamber  30 , sample/calibration flow path  32  which is coupled to a detector, sample out flow  34 , sample pressure channel  36  and a flow cell  38  which is a detection chamber.  
         [0052]     Cartridges  20  can have wet and dry chemistries and at least one substrate that carriers a chemistry. Examples of various wet and dry chemistries are listed in Table 1.  
                               TABLE 1                                   Cartridge   Wet Reagents   Dry Reagents                           electrolytes   calibration fluid   ion specific electrodes           immunology   —   Capture antibody                   Conjugate antibody           hemolotogy   Lysing solution/white   —               blood cell - nuclear label               Hemoglobin dye           Chemistry   Various   Various           Coagulation   —   Initiator           Blood gas   —   Electrode           Molecular   Nucleic acid label   Nucleic acid capture                   Amplification reagents                      
 
         [0053]     Cartridges  20  are associated with a corresponding module  12 . In one embodiment, cartridges  20  can directly accept a blood sample from a standard blood draw, sample tube  40  which can include a pressure needle  42  and a sampling needle  44 , as shown in  FIG. 3 . This can be achieved by, (i) piercing the cap of the standard blood draw tube  40  needles  42  and  44 , which deliver low pressure air to force the sample through the other needle into the cartridge  20 , penetrating the cap with a single needle and withdrawing fluid directly using a vacuum, and the like. Cartridges  20  can be configured to retain and seal fluids. This can be achieved by using selective pressurization of reagent and sample reservoirs, which forces the fluids into cartridges  20  and through flow cell  38  into waste chamber  30 , that can be an integral part of cartridges  20 . All fluids in cartridges  20 , including patient samples, can remain within the cartridge  20 .  
         [0054]     As illustrated in  FIG. 4 , modules  12  can be configured to be engaged with the cartridges  20  to produce pneumatic movement of fluids in the cartridges  20 . The pneumatic pressure is applied by an external pump  46  through the dock  22  on cartridge  20 ,  FIG. 2 , which is engaged by module  12 . Module  12  can include a valve,  48 , a vent  50  to atmosphere and a channel  52  that is coupled to cartridge  20 . The pneumatic pressure is directed to specific reservoirs and samples in cartridge  20  using valve  48  mechanism to cause selective reagent flow. Cartridge  20  includes a sample application area  54 . Optics  56  are included in module  12  and an optical window  57  is included in cartridge  20 . At the cessation of reagent flow, excess pressure is vented through vent  50  to atmosphere to stop the flow. Platform  10  can provide self-testing of modules  12 , to provide for monitoring and detection of fluid flow. Various electrical and optical properties of the samples and reagents allow continuous monitoring of flow cell contents and are compared to expected transition values, as illustrated in  FIG. 5 .  
         [0055]      FIG. 6  illustrates a cross-sectional view of one embodiment of a cartridge  20 . Cartridge  20  can have a number of different flow channels, including but not limited to air, sample and reagent flow channels  58 ,  60  and  62 . Flow channels  58 - 62  can be created by depressions in both the top and bottom surfaces of the cartridge  20 . Flow paths  58 - 62  can then be sealed with a vapor barrier  64 .  
         [0056]     Referring again to  FIG. 4 , pressurization of specific sample or reagent containers provided by pump  46  are selectively directed to sample and reagents containers in sequence, providing an outflow directed by a valve to detection chamber  38  or other location, as needed, in sequence and with precise timing. The sample and reagents can flow through an area of controlled temperature to prepare them for precise analysis prior to or during introduction to detection chamber  38 . After analysis the reagents and sample remain in the cartridge  20  in waste region  30 , although the sample tube  40  can be removed by the operator for subsequent use if desired.  
         [0057]     Each module  12  can include a processor  56  ( FIG. 1 ( b ). Host computer  16 , in combination with a processor  56 , determines a test protocol for a cartridge  20 . A fluid control mechanism in the cartridge  20  is then actuated that permits a flow of a patient sample with liquid chemistries and waste materials. This can occur without exposing an operator of platform  10  and the patient, to a transfer of a patient sample into the cartridge  20  without exposure to the chemistries. Cartridges  20  are designed to isolate biohazards in a cartridge  20  from an operator of the cartridge  20  or the patient. Blood samples from patients are introduced to the cartridges  20  while isolating biohazards in the cartridge from an operator.  
         [0058]     In one embodiment, cartridges  20  are designed to work with whole blood. This eliminates the requirement of a secondary process to remove the cellular components which may interfere with the testing. This additional separation is both time consuming and error prone. In the cartridge, the separation of cells is done automatically by providing a barrier which is penetrated by the analyte to be measured by excludes the cells from analytical contact, except in the case of hemotalogy, where the cells themselves are the subject of measurement.  
         [0059]     Cartridges  20  can include electronic identifiers, including but not limited to bar-coded identifiers, with information for test protocols, and lot expiration dates. Cartridges  20  can also include serialized identification.  
         [0060]     In one embodiment, placement of a cartridge  20  in a module  12  begins an initiation of the module  12 . When a cartridge  20  is inserted into a module  12  it can be sensed automatically. The bar code of cartridge  20 , with its unique sample, are read. This initiates the sequential operation of the fluid movement and detection.  
         [0061]     In another embodiment of the present invention, platform  10  includes a plurality of modules  12  each sharing common QC protocols. A list of possible QC protocols is found in table 2.  
                                                                                                           TABLE 2                                   Responsibility   Comments                                    Model POCT Platform Operating Procedures            Action (per cartridge)               1. Draw minimum of 1.5 ml whole blood   Operator   Exact volume above       Operator Exact volume sample in       minimum not critical       appropriate 5 ml vacutainer-type above       minimum not draw tube, using standard       draw procedure       2. Push sample tube into cartridge tube   Operator       dock and fully seat over needles       3. Place patient ID bar code label in   Operator   If ED bar code system       designated target area on tube dock       used       4. Push cartridge into module port until   Operator*   Platform in testing       fully seated over snap-type detents       mode       5. LED (blue) above port flashes to   Platform   No LED, push       indicate cartridge fully seated in port       cartridge further into       and cartridge further read in process       port       6. LED steady illumination after 2       No steady LED,       seconds if cartridge read OK (lot#, exp.       replace cartridge and       Date, test type, patient ID) OPERATOR       reuse sample       WALK AWAY and reuse sample       7. Perform designated assay protocol       10-15 minutes       8. LED extinguishes, patient, test       Downloaded to LIS       results, reference range and QC data       when connected       stored in memory, displayed on screen       and printed on attached printer       9. Remove cartridge and discard in       biohazardous solid waste (remove and       sale sample tube if required)            Immunoassay            Action               1. Draw minimum of 1.5 ml whole blood   Operator   Exact volume above       Operator Exact volume sample in       minimum not critical       appropriate 5 ml vacutainer-type above       minimum not draw tube, using standard       draw procedure       2. Push sample tube into cartridge tube   Operator       dock and fully seat over needles       3. Place patient ID bar code label in   Operator   If ED bar code system       designated target area on tube dock       used       4. Push cartridge into module port until   Operator       fully seated over snap-type detents       5. Pressurize sample tube and flow   Platform   3X volume for (3) strip       sample: 200 ul/test trip at 500 u./min       cartridge       6. Stop flow by:   Platform   Test strip manifold is a       a. venting pressure to test strip       porous membrane       manifold, or       b. flow channel manifold if even       distribution       7. Read reflectance change on strip   Platform       reaction areas at designated intervals            Hemotology            1. Draw minimum of 1.5 ml whole blood   Operator   Exact volume above       Operator Exact volume sample in       minimum not critical       appropriate 5 ml vacutainer-type above       minimum not draw tube, using standard       draw procedure       2. Push sample tube into cartridge tube   Operator       dock and fully seat over needles       3. Place patient ID bar code label in   Operator   If ED bar code system       designated target area on tube dock       used       4. Push cartridge into module port until   Operator       fully seated over snap-type detents       5. Pressurize sample tube and flow   Platform       sample to segment at 200 ul       6. Stop flow by venting pressure to   Platform       sample tube       7. Pressurize diluent and flow to wash   Platform       sample segment into mixing chamber       8. Stop flow by venting pressure   Platform   How mix       9. Mix sample and diluent   Platform       10. Pressurize mixed sample and flow   Platform       to flowcell.       11. Stop flow by venting pressure   Platform       12. Repeat steps 10 and 11 (4) times   Platform       13. Segment 50 ul of sample   Platform       14. Mix with 500 ul of Hb reagent   Platform       15. Flow mixed sample into flowcell:   Platform       100 ul at 1 ml/min            Electrolytes            1. Draw minimum of 1.5 ml whole blood   Operator   Exact volume above       Operator Exact volume sample in       minimum not critical       appropriate 5 ml vacutainer-type above       minimum not draw tube, using standard       draw procedure       2. Push sample tube into cartridge tube   Operator       dock and fully seat over needles       3. Place patient ID bar code label in   Operator   If ED bar code system       designated target area on tube dock       used       4. Push cartridge into module port until   Operator       fully seated over snap-type detents       5. Pressurize sample tube and flow   Platform       sample to segment: 300 ul at 2 ml/min.       6. Stop flow by venting pressure   Platform       7. Pressurize sample tube and flow   Platform       sample through cartridge: 400 ul at 3 ml/min.       8. Stop flow by venting pressure   Platform                 *Operation at Instrument             
 
         [0062]      FIGS. 8 through 11  are flow charts illustrating point of care diagnostic platform  10  of the present invention.  FIG. 8  is a flow chart illustrating an overall methodology of the point of care diagnostic platform of the present invention.  FIG. 9  is a flow chart illustrating one embodiment of a cartridge processing procedure implemented with the point of care diagnostic platform of the present invention.  FIG. 10  is a flow chart illustrating one embodiment of an immunoassay operating procedure implemented with the point of care diagnostic platform of the present invention.  FIG. 11  is a flow chart illustrating one embodiment of a hematology operating procedure implemented with the point of care diagnostic platform of the present invention.  
         [0063]     In the preceding example, all reagents and waste are contained in cartridge  20 . Fluids are moved in cartridge  20  via an external pump (in the module) coupled to cartridge  20  via an air dock. Likewise the reagents and sample are directed sequentially by valve(s) with-in the cartridge but activated through physical engagement to an external activator in the module. Cartridge  20  contains the fluid flow, fluid distribution fluid segmentation and sample dilution. A module  12  controls the fluid flow via a low pressure air connection and the fluid selection via one or more valve connections.  
         [0064]     In another embodiment, platform  10  provides real time QC monitoring, and real time test result threshold detection, as disclosed in U.S. Provisional No. 60/470,725, incorporated herein by reference.  
         [0065]     While embodiments of the invention have been illustrated and described, it is not intended that these embodiments illustrate and describe all possible forms of the invention. Rather, the words used in the specification are words of description rather than limitation, and it is understood that various changes may be made without departing from the spirit and scope of the invention.