Method and instrument for automatically performing analysis relating to thrombosis and hemostasis

Claim 3

The method according to claim 1, further comprising independently defining a test protocol for each assay.

Claim 4

The method according to claim 2, wherein the test protocol includes mechanical instructions, optical instructions, data analysis and quality assurance parameters.

Claim 5

The method according to claim 1, further comprising automatically diluting the transferred sample.

Claim 6

The method according to claim 1, further comprising: a) controlling a cooling unit and maintaining each sample initially within a low temperature range having a predetermined maximum temperature; b) controlling a heating unit that maintains each sample within a predetermined measuring temperature range that is higher than the initial temperature range; c) transitioning the temperature of each sample from the initial range to the measuring temperature; d) reducing an effect of ambient temperature on each sample; and e) delivering reagents to each test well at a specified temperature.

Claim 7

The method according to claim 1, wherein after dispensing a sample or reagent into a well, a sample preparation means for automatically selecting and adding the reagents for the scheduled assays is washed by a wash liquid.

Claim 8

The method according to claim 6, wherein the wash liquid is selected from a group consisting of water, wash solution and bleach solution.

Claim 9

The method according to claim 1, further comprising evaluating data obtained from each assay by a) calculating a second derivative of a process signal and determining the peak thereof, which is an indication of maximum acceleration of clot formation; or b) calculating a magnitude of change of a process signal; or c) calculating a rate of change of a parameter, whereby a first derivative of the parameter is determined; or d) a combination of the calculations of a)-c) above.

Claim 10

The method according to claim 1, wherein the data is transformed by normalization and calibration to standardized material by a numerical construction of a system model using known reference material, specific for each assay.

Claim 11

The method according to claim 9, further comprising a system model developed from a function with a linear or nonlinear relationship between recovered and reported values, the function created by fitting to a set of sample data.

Claim 12

The method according to claim 1, comprising a quality assurance protocol for monitoring and evaluating the sample handling, sample preparation, reaction detection and results reported for the sample, wherein the quality assurance protocol comprises checks for sample integrity, reagent integrity, mechanical suitability and optical quality.

Claim 13

The method according to claim 11, wherein the check for sample integrity comprises detecting at least one preanalytical variable in the sample selected from lipemia, bilirubin and hemolysis.

Claim 14

The method according to claim 11, wherein the check for reagent integrity comprises evaluating control material and applying statistical quality control rules and a comparison of a current result to an earlier sample result.

Claim 15

The method according to claim 11, wherein the check for system suitability comprises measuring electrical, volumetric and thermal output of critical mechanical components.

Claim 16

The method according to claim 11, wherein the check for optical quality comprises monitoring an optical reference clot at an appropriate wavelength and monitoring the signal to noise ratio, thereby insuring the use of acceptable signals.

Claim 17

An instrument for automatically performing qualitative and quantitative coagulation, chromogenic and immunological assays for hemostasis and thrombosis parameters on each of a multiplicity of samples of plasma, serum or whole blood, whereby each sample is selected for assay on a random access basis without a drop in speed of sample through-put, comprising: a) a programming input device for identifying each of a multiplicity of samples, and means for selecting each sample and scheduling one or more hemostasis and thrombosis assays to be performed on each sample on a random access basis; b) a plurality of test wells for a plurality of assays and a specimen handling means for automatically transferring at a sample insertion station an aliquot of each sample from a holding device to a respective test well of said plurality of test wells; c) a fully automated sample preparation means for automatically selecting and adding reagents needed for a plurality of qualitative and quantitative coagulation, chromogenic and immunological assays to measure hemostasis or thrombosis parameters of the samples in the test wells, a first reagent delivery probe station being provided where a diluent or reagent is optionally added to a test well depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said first reagent delivery probe station in a predetermined first constant time after the sample is delivered to the test well at said sample insertion station, said sample preparation means comprising means for varying at said first reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; a second reagent delivery probe station being provided where a reagent is optionally added depending upon the type of assay being performed on the particular sample in the test well, the test well being disposed at said second reagent delivery probe station in a predetermined second constant time after the test well passes through said first reagent delivery probe station, said sample preparation means comprising a means for varying at said second reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; an optical monitoring station being provided where a reaction of the sample and one or more reagents is monitored by an optical monitoring system for measuring changes in the optical transmission of the sample, said test well reaching said optical monitoring station in a predetermined third constant time after the test well passes through said second reagent delivery probe station, and wherein each of said predetermined constant times remains the same regardless of the hemostasis or thrombosis assay being performed on the sample; said optical monitoring system comprising a detector for detecting the reaction in each test well and measuring the data from each reaction, a processor for mathematically processing the measured data to evaluate a change in or magnitude of the measured data from the reaction in the well, and a reporter to report results of processing the measured data by the processor.

Claim 18

An instrument for automatically performing qualitative and quantitative coagulation, chromogenic and immunological assays for hemostasis and thrombosis parameters on each of a multiplicity of samples of plasma, serum or whole blood, whereby each sample is selected for assay on a random access basis without a drop in speed of sample through-put, comprising: a) a programming input device for identifying each of a multiplicity of samples, and means for selecting each sample and scheduling one or more hemostasis and thrombosis assays to be performed on each sample on a random access basis; b) a plurality of test wells for a plurality of assays and a specimen handling means for automatically transferring at a sample insertion station an aliquot of each sample from a holding device to a respective test well of said plurality of test wells; c) a fully automated sample preparation means for automatically selecting and adding reagents needed for a plurality of qualitative and quantitative coagulation, chromogenic and immunological assays to measure hemostasis or thrombosis parameters of the samples in the test wells, a first reagent delivery probe station being provided where a diluent or reagent is optionally added to a test well depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said first reagent delivery probe station in a predetermined first constant time after the sample is delivered to the test well at said sample insertion station, said sample preparation means comprising means for varying at said first reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; a second reagent delivery probe station being provided where a reagent is optionally added depending upon the type of assay being performed on the particular sample in the test well, the test well being disposed at said second reagent delivery probe station in a predetermined second constant time after the test well passes through said first reagent delivery probe station, said sample preparation means comprising a means for varying at said second reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; an optical monitoring station being provided where a reaction of the sample and one or more reagents is monitored by an optical monitoring system for measuring changes in the optical transmission of the sample, said test well reaching said optical monitoring station in a predetermined third constant time after the test well passes through said second reagent delivery probe station, and wherein each of said predetermined constant times remains the same regardless of the hemostasis or thrombosis assay being performed on the sample; said optical monitoring system comprising a detector for detecting the reaction in each test well and measuring the data from each reaction, a processor for mathematically processing the measured data to evaluate a change in or magnitude of the measured data from the reaction in the well, and a reporter to report results of processing the measured data by the processor.

Claim 19

The instrument according to claim 16, wherein additionally is included a means for independently defining required steps for each assay.

Claim 20

The instrument according to claim 19, wherein instructions for a scheduled assay include mechanical instructions, optical instructions, data analysis and quality assurance parameters.

Claim 21

The instrument according to claim 16, wherein additionally is included a diluting device for automatically diluting the transferred sample.

Claim 22

The instrument according to claim 16, further comprising: a) a cooling controller for independently controlling a cooling unit, maintaining each sample initially within a low temperature range having a predetermined maximum temperature; b) a heating controller for independently controlling a heating unit that maintains each sample in an optically monitored section within the detector, within a predetermined measuring temperature range that is higher than the initial temperature range; c) a transitioning device for transitioning each sample from the initial range to the measuring temperature; d) a reducing device for reducing the effect of ambient temperature on each sample; and e) a transport mechanism for delivering reagents to the test well at a specified temperature.

Claim 23

The instrument according to claim 16, further comprising a washing mechanism wherein following each time a sample or reagent is dispensed into a well, the sample preparation means is washed by the washing mechanism with a wash liquid.

Claim 24

The instrument according to claim 21, wherein the wash liquid is selected from a group consisting of water, wash solution or bleach solutions.

Claim 25

The instrument according to claim 16, further comprising a computational means for evaluating data obtained from each assay, the computational means comprising: a) means for calculating a second derivative of a process signal and determining the peak thereof, which is an indication of maximum acceleration of clot formation; or b) means for calculating a magnitude of change of a process signal; or c) means for calculating a rate of change of a parameter, whereby a first derivative of the parameter is determined; or d) a combination of the means for calculating of a)-c) above.

Claim 26

The instrument according to claim 16, wherein the change in or magnitude of the data is measured by a means for normalization and calibration to standardized material by a numerical construction of a system model using known reference material, specific for each assay.

Claim 27

The instrument according to claim 24, further comprising a system model developed from a function with a linear relationship between recovered and reported values, the function created by fitting to a set of sample data.

Claim 28

The instrument according to claim 16, wherein a quality assurance means is provided comprising a means for checking for sample integrity, reagent integrity, mechanical suitability and optical quality.

Claim 29

The instrument according to claim 26, wherein the means for checking for sample integrity comprises detecting preanalytical variables in the sample.

Claim 30

The instrument according to claim 26, wherein the means for checking for reagent integrity comprises evaluating control material and applying statistical quality control rules and a comparison of a current result to a earlier sample result.

Claim 31

The instrument according to claim 26, wherein the means for checking for mechanical suitability comprises a means for measuring electrical, volumetric and thermal output of mechanical components of said instrument.

Claim 32

The instrument according to claim 26, wherein the means for checking for optical quality comprises a means for monitoring an optical reference clot at an appropriate wavelength inspection and monitoring a signal to noise ratio.

Claim 33

The method of claim 1, wherein a plurality of cuvettes are provided, each comprising a plurality of said test wells, and wherein different assays selected from said qualitative and quantitative coagulation, chromogenic and immunological assays for measuring hemostasis or thrombosis parameters are performed on one or more samples in different test wells of the same cuvette.

Claim 34

The method of claim 1, wherein said different assays comprise Partial Thromboplastin Time, Prothrombin Time, Activated Partial Thromboplastin Time and Factor deficiency assays.

Claim 35

The method of claim 1, wherein said first and second predetermined constant times are about two minutes and forty seconds.

Claim 38

The method of claim 34, wherein a plurality of cuvettes are provided, each comprising a plurality of said test wells, and wherein said different assays for measuring thrombosis or hemostasis parameters are performed on one or more samples in different test wells of the same cuvette.

Claim 39

The method of claim 34, wherein said different assays comprise Partial Thromboplastin Time, Prothrombin Time, Activated Partial Thromboplastin Time and Factor deficiency assays.

Claim 40

The method of claim 34, wherein said first and second predetermined constant times are about two minutes and forty seconds.

Claim 41

An instrument for automatically performing assays to measure hemostasis or thrombosis parameters, comprising: a) a programming input device for identifying each of a plurality of samples and selecting each sample and scheduling one or more of hemostasis and thrombosis assays to be performed on each sample; b) a plurality of test wells for a plurality of assays and a specimen handler for automatically transferring at a sample insertion station an aliquot of each sample from a holding device to a respective test well of said plurality of test wells; c) a sample preparation device for automatically selecting and adding reagents needed for a plurality of different scheduled assays to measure hemostasis or thrombosis parameters of the samples in the test wells, a first reagent delivery probe station being provided where a diluent or reagent is optionally added to a test well depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said first reagent delivery probe station in a predetermined first constant time after the sample is delivered to the test well at said sample insertion station, said sample preparation means comprising means for varying at said first reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon Which thrombosis or hemostasis assay is being performed; a second reagent delivery probe station being provided where a reagent is optionally added depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said second reagent delivery probe station in a predetermined second constant time after the test well passes through said first reagent delivery probe station, said sample preparation means comprising a means for varying at said second reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; an optical monitoring station being provided where a reaction of the sample and one or more reagents is monitored by an optical monitoring system for measuring changes in an optical transmission of the sample, said test well reaching said optical monitoring station in a predetermined third constant time after the test well passes through said second reagent delivery probe station, and wherein each of said predetermined constant times remains the same regardless of the hemostasis or thrombosis assay being performed on the sample, and wherein a temperature at which said path is maintained is constant from assay to assay and the rate at which the test wells are moved along the path by said mover does not vary from assay to assay such that different hemostasis and thrombosis assays can be randomly, continuously and substantially concurrently performed on a fully automated, random access basis; said optical monitoring system comprising a detector for detecting the reaction in each test well and measuring data from each reaction, a processor for mathematically processing the measured data to evaluate a change in or magnitude of the measured data from the reaction in the well, and reporting results of processing the measured data.

Claim 42

An instrument for automatically performing assays to measure hemostasis or thrombosis parameters, comprising: a) a programming input device for identifying each of a plurality of samples and selecting each sample and scheduling one or more of hemostasis and thrombosis assays to be performed on each sample; b) a plurality of test wells for a plurality of assays and a specimen handler for automatically transferring at a sample insertion station an aliquot of each sample from a holding device to a respective test well of said plurality of test wells; c) a sample preparation device for automatically selecting and adding reagents needed for a plurality of different scheduled assays to measure hemostasis or thrombosis parameters of the samples in the test wells, a first reagent delivery probe station being provided where a diluent or reagent is optionally added to a test well depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said first reagent delivery probe station in a predetermined first constant time after the sample is delivered to the test well at said sample insertion station, said sample preparation means comprising means for varying at said first reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon Which thrombosis or hemostasis assay is being performed; a second reagent delivery probe station being provided where a reagent is optionally added depending upon the type of assay being performed on the sample in the test well, the test well being disposed at said second reagent delivery probe station in a predetermined second constant time after the test well passes through said first reagent delivery probe station, said sample preparation means comprising a means for varying at said second reagent delivery probe station the type of reagent and the volume and temperature of the reagent depending upon which thrombosis or hemostasis assay is being performed; an optical monitoring station being provided where a reaction of the sample and one or more reagents is monitored by an optical monitoring system for measuring changes in an optical transmission of the sample, said test well reaching said optical monitoring station in a predetermined third constant time after the test well passes through said second reagent delivery probe station, and wherein each of said predetermined constant times remains the same regardless of the hemostasis or thrombosis assay being performed on the sample, and wherein a temperature at which said path is maintained is constant from assay to assay and the rate at which the test wells are moved along the path by said mover does not vary from assay to assay such that different hemostasis and thrombosis assays can be randomly, continuously and substantially concurrently performed on a fully automated, random access basis; said optical monitoring system comprising a detector for detecting the reaction in each test well and measuring data from each reaction, a processor for mathematically processing the measured data to evaluate a change in or magnitude of the measured data from the reaction in the well, and reporting results of processing the measured data.

Claim 43

The method of claim 1, wherein prior to said test well reaching said optical monitoring system, said test well passes through a third reagent delivery probe station where a reagent is optionally added depending upon the type of assay being performed on the particular sample in the test well, the type of reagent and the volume and temperature of the reagent being variable depending upon which thrombosis or hemostasis assay is being performed.

Claim 44

The method of claim 34, wherein prior to said test well reaching said optical monitoring system, said test well passes through a third reagent delivery probe station where a reagent is optionally added depending upon the type of assay being performed on the particular sample in the test well, the type of reagent and the volume and temperature of the reagent being variable depending upon which thrombosis or hemostasis assay is being performed.