WO2001011356A2

WO2001011356A2 - Methods and apparatus for determining coagulation times

Info

Publication number: WO2001011356A2
Application number: PCT/US2000/020853
Authority: WO
Inventors: Charles W. Bolam; Greg Paul Carpenter; Danny R. Gibbs; Kurt Gerard Klem; Gary T. Neel; Marshall M. Parker; Morris J. Young
Original assignee: Roche Diagnostics Corporation
Priority date: 1999-08-06
Filing date: 2000-08-01
Publication date: 2001-02-15
Also published as: WO2001011356A3

Abstract

An instrument (20) and a method for determining a characteristic of a sample of a biological fluid (blood) or a control includes a first source (64) providing radiation for transmission through a region of the sample and a second source (56, 58) providing heat for maintaining the sample at a desired temperature. The second source includes a plate (58) having first and second generally opposite sides. The plate (58) includes a material which is not opaque. The first source (64) is mounted (65) on the first side of the plate (58) and the sample is disposed on the second side of the plate (58) during the determination of the characteristic. The radiation passes through the non-opaque material and into the sample and is then detected in order to determine the characteristic.

Description

METHODS AND APPARATUS FOR DETERMINING COAGULATION TIMES

Background of the Invention

This invention is disclosed in the context of methods and apparatus for determining blood coagulation times. However, it is believed to have utility in other fields as well.

Field of the Invention

A number of systems and methods for the determination of blood coagulation times are known. There are, for example, the systems and methods disclosed in U.S. Patents Nos.: 4,756,884; 4,849,340; 4,963,498; 5,110,727;

5,140,161; 5,522,255; 5,686,659; 5,710,622; 5,789,664; 5,792,944; 5,832,921; and,

5,841,023. The disclosures of U.S. Patents Nos. 5,522,255; 5,686,659; 5,710,622;

5,789,664; 5,792,944; 5,832,921; and, 5,841,023 are hereby incorporated by reference. This listing is not intended as a representation that a thorough search of the prior art has been conducted or that no more pertinent art than that listed above exists, and no such representation should be inferred.

Disclosure of the Invention According to one aspect of the invention, an instrument for determining a characteristic of a sample of a biological fluid or a control includes a first source for providing radiation for transmission through a region of the sample and a second source for providing heat for maintaining the sample at a desired temperature. The second source includes a plate having first and second generally opposite sides. The plate includes a material which is not opaque. The first source is mounted on the first side of the plate and the sample is disposed on the second side of the plate during the determination of the characteristic. The radiation passes through the non-opaque material and into the sample and is then detected in order to determine the characteristic. According to another aspect of the invention, an instrument for determining a characteristic of a sample of a biological fluid or a control includes a source for providing radiation for illuminating the sample in order to determine the characteristic. The source is one selected from among a plurality of sources which provide different radiation output in response to the same input power. The apparatus further includes a power supply coupled to the source. The power supply selectively provides different levels of power to the source in order to provide a desired radiation output.

According to another aspect of the invention, an instrument for determining a characteristic of a sample of a biological fluid or a control includes a switching power supply.

According to another aspect of the invention, an instrument for determining a characteristic of a sample of a biological fluid or a control includes a source for providing radiation for transmission through a region of the sample. The instrument includes a detector for detecting the radiation transmitted through the sample, and a controller coupled to the detector for determining when a characteristic of the transmitted radiation drops below a threshold and determimng the characteristic based upon the time required for the transmitted radiation to drop below the threshold.

Illustratively according to these aspects of the invention, the first source includes a light emitting diode (LED) mounted with its light emitting region facing away from the first side and a reflective material for reflecting light back toward the first side. Illustratively, the first source includes an LED which emits infrared radiation.

Further illustratively according to these aspects of the invention, the second source includes a heater element provided on the first side of the plate.

Illustratively, the heater element is thermally insulated from the first source to reduce thermal variation of the radiation output from the first source.

Additionally illustratively according to these aspects of the invention, a controller is provided for controlling the heater element. The controller includes a temperature sensing device for sensing the temperature of the plate.

Illustratively according to these aspects of the invention, the controller controls the heat source according to an algorithm including a parameter which varies from instrument to instrument. The apparatus further includes a port through which the parameter can be entered into the controller to control the second source. Further illustratively according to these aspects of the invention, a first power supply is coupled to the heater element. The first power supply includes a switching power supply.

Illustratively, the switching power supply includes a pulsewidth modulated power supply.

Additionally illustratively according to these aspects of the invention, the first source is one selected from among a plurality of first sources which provide different radiation output in response to the same input power. The apparatus further includes a first power supply coupled to the first source. The first power supply selectively provides different levels of power to the first source in order to provide a desired radiation output.

Illustratively according to these aspects of the invention, the first power supply includes a voltage divider. The voltage divider includes a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements. Each of the second divider elements is coupled in circuit with a respective one of the switches. Each of the switches has a control input for actuating that respective switch to place its respective second divider element in circuit with the first divider element to divide a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output. Illustratively, multiple ones of the switches can be actuated simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

Illustratively, the respective multiple ones of the second divider elements are placed in parallel with one another when their respective ones of the switched are actuated simultaneously.

Further illustratively according to these aspects of the invention, the apparatus includes a source for providing heat for maintaining the sample at a desired temperature. Illustratively, a controller is provided for controlling the heat source.

The controller includes a temperature sensing device for sensing the temperature of the heat source. Illustratively, the controller controls the heat source according to an algorithm including a parameter which varies from instrument to instrument. The apparatus further includes a port through which the parameter can be entered into the controller to control the heat source of the apparatus. Illustratively, the port is a serial port.

Illustratively, the port is an RS-232 port.

Additionally illustratively according to these aspects of the invention, the controller measures the elapsed time that the transmitted radiation has been above the threshold, the controller establishing a maximum elapsed time. The controller determines when the elapsed time reaches the maximum elapsed time and determines the characteristic based upon the detected radiation when the elapsed time reaches the maximum elapsed time.

Illustratively according to these aspects of the invention, the controller determines from the characteristic of the transmitted radiation whether the applied sample is a sample of a biological fluid or whether the applied sample is a sample of a control.

Further illustratively according to these aspects of the invention, the instrument determines the characteristic by combining the biological fluid or control with nontransparent ferromagnetic particles, subjecting the combination to a time varying magnetic field, and detecting the modulation of the transmittance of radiation through the combination.

According to another aspect of the invention, a method of determining a characteristic of a sample of a biological fluid or a control includes transmitting radiation through a region of the sample, and maintaining the sample at a desired temperature. Transmitting radiation through a region of the sample includes providing a plate having first and second generally opposite sides. The plate includes a material which is not opaque. The method includes transmitting radiation from the first side of the plate, placing the sample on the second side of the plate during the determination of the characteristic, and passing the radiation through the non-opaque material and into the sample and then detecting the radiation in order to determine the characteristic. According to another aspect of the invention, a method for determining a characteristic of a sample of a biological fluid or a control includes providing radiation from a source of such radiation for illuminating the sample in order to determine the characteristic. The source is one selected from among a plurality of such sources which provide different radiation output in response to the same input power. The method further includes coupling a power supply selectively providing different levels of power to the radiation source. The power supply selectively provides a level of power to the radiation source in order to provide a desired radiation output from the radiation source. According to another aspect of the invention, a method of operating an instrument for determining a characteristic of a sample of a biological fluid or a control includes providing in the instrument a switching power supply.

According to another aspect of the invention, a method for determining a characteristic of a sample of a biological fluid or a control includes providing an instrument including a source for providing radiation for transmission through a region of the sample, providing in the instrument a detector for detecting the radiation transmitted through the sample, and providing in the instrument a controller coupled to the detector for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold. Illustratively according to these aspects of the invention, transmitting radiation from the first side of the plate includes mounting a light emitting diode (LED) with its light emitting region facing away from the first side, and applying a reflector to the light emitting region to reflect light back toward the first side.

Illustratively, transmitting radiation includes transmitting infrared radiation.

Illustratively, maintaining the sample at a desired temperature includes providing a heater element on the first side of the plate.

Further illustratively according to these aspects of the invention, transmitting radiation through a region of the sample includes transmitting radiation from a first source of such radiation through a region of the sample. The method further includes thermally insulating the heater element from the first source to reduce thermal variation of the radiation output from the first source. Additionally illustratively according to these aspects of the invention, controlling the heater element includes sensing the temperature of the plate.

Illustratively according to these aspects of the invention, controlling the heater element includes controlling the heater element according to an algorithm including a parameter which varies from instrument to instrument. The method further includes providing a port through which the parameter can be entered into the algorithm.

Further illustratively according to these aspects of the invention, the method includes supplying power to the heater element from a switching power supply.

Illustratively, supplying power to the heater element from a switching power supply includes supplying power to the heater element from a pulsewidth modulated power supply.

Additionally illustratively according to these aspects of the invention, transmitting radiation from the first side of the plate includes transmitting radiation from a first source selected from among a plurality of first sources which provide different radiation output in response to the same input power. The method further includes selectively providing different levels of power to the first source in order to provide a desired radiation output. Illustratively, selectively providing different levels of power to the first source includes providing a voltage divider including a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements, coupling each of the second divider elements in circuit with a respective one of the switches, providing for each of the switches a control input for actuating that respective switch to place its respective second divider element in circuit with the first divider element, and thereby dividing a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

Illustratively, actuating respective switches to place their respective second divider elements in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

Illustratively, actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in parallel with one another.

Illustratively according to these aspects of the invention, providing in the instrument a switching power supply includes providing in the instrument a pulsewidth modulated power supply.

Further illustratively according to these aspects of the invention, the sample is maintained at a desired temperature by a heat source.

Additionally illustratively according to these aspects of the invention, providing in the instrument a controller includes providing a temperature sensing device for sensing the temperature of the heat source for controlling the heat source.

Illustratively according to these aspects of the invention, providing in the instrument a controller for controlling the heat source includes providing in the instrument a controller for controlling the heat source according to an algorithm including a parameter which varies from instrument to instrument. The method further includes providing on the instrument a port and entering the parameter through the port.

Illustratively, providing on the instrument a port includes providing on the instrument a serial port.

Illustratively, providing on the instrument a port includes providing on the instrument an RS-232 port.

Further illustratively according to these aspects of the invention, providing in the instrument a controller for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold includes providing a controller which measures the elapsed time that the transmitted radiation has been above the threshold. The method further includes establishing a maximum elapsed time, determining when the elapsed time reaches the maximum elapsed time, and determining the characteristic based upon the detected radiation when the elapsed time reaches the maximum elapsed time.

Illustratively, providing in the instrument a controller for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold includes providing a controller for determining from the characteristic of the transmitted radiation whether the applied sample is a sample of a biological fluid or whether the applied sample is a sample of a control.

Illustratively according to these aspects of the invention, providing an instrument for determining a characteristic of a sample of a biological fluid or a control includes providing an instrument for determining a characteristic of a sample of a biological fluid or a control by combining the biological fluid or control with nontransparent ferromagnetic particles, subjecting the combination to a time varying magnetic field, and detecting the modulation of the transmittance of radiation through the combination. Illustratively according to the various aspects of the invention, the biological fluid is blood or a blood fraction, and the characteristic of the biological fluid is a clotting time.

Brief Description of the Drawings The invention may best be understood by referring to the following detailed description and accompanying drawings which illustrate the invention. In the drawings:

Figs, la-b illustrates partly exploded perspective views of an instrument constructed according to the present invention; Fig. 2 illustrates a much enlarged plan view of a detail of the instrument illustrated in Figs, la-b;

Fig. 3 illustrates an enlarged, exploded perspective view of a detail of the instrument illustrated in Figs, la-b;

Figs. 4-5 illustrate enlarged, exploded top and bottom perspective views, respectively, of a detail of the instrument illustrated in Figs, la-b;

Fig. 6 illustrates an enlarged front elevational view of a detail of the instrument illustrated in Figs, la-b, with all segments activated; and, Figs. 7a-kk illustrate circuits useful in the instrument illustrated in Figs. la-b.

Detailed Description of an Illustrative Embodiment In the detailed descriptions that follow, several integrated circuits and other components are identified, with particular circuit types and, in some cases, sources. In many cases, terminal names and pin numbers for these specifically identified circuit types and sources are noted. This should not be interpreted to mean that the identified circuits are the only circuits available from the same, or any other, sources that will perform the described functions. Other circuits are typically available from the same, and other, sources which will perform the described functions. The terminal names and pin numbers of such other circuits may or may not be the same as those indicated for the specific circuits identified in this application.

Referring to Figs, la-b, an instrument 20 is intended for use with strips 21 of the general types, and for the purposes described in, for example, international publications WO 95/06868 published 09 march 1995 and WO 99/41147 published 19 August 1999, the disclosures of which are incorporated herein by reference, for the determination of clotting times. Instrument 20 is of a size (about 16.5 cm by about 12.7 cm by about 4.5 cm) which is capable of being hand-held, and includes an instrument case 22 having an upper portion 24 and a lower portion 26. The upper portion 24 is provided with a display window 28 through which a liquid crystal display (LCD) 30 (see also Figs. 6 and 7q) is viewable. LCD 30 is mounted on a support/spacer 31 which includes recesses 33 for housing elastomeric connector strips 35 for making the electrical connections between LCD 30 and other instrument 20 electrical circuits, to be described. LCD 30 is held to support/spacer 31 by a bezel 37 which connects to a printed circuit board (PCB) 39. Some of the circuitry of instrument 20 is provided on PCB 39.

An on off switch 34 (see also Fig. 7c) and a memory recall switch 36 (see also Fig. 7b) formed in a common silicone pad are accessible through openings provided therefor in a lid 32. A set button 38 (see also Fig. 7s) for the icon-based

LCD 30 is mounted at the intersection of the upper and lower portions 24, 26 of case 22 on a back surface 40 of the instrument 20. A PCB 42 on which is provided some of the circuitry for instrument 20 is mounted in the lower portion 26. An electromagnet 44 is mounted by a spring clip 46 to a strip adapter subassembly 48. A heater plate assembly 50 (see also Fig. 2) is also mounted to the strip adapter subassembly 48. Lid 32 is hinged to strip adapter subassembly 48 to permit lid 32 to be opened to provide access to the area where strips 21 are inserted for tests for cleaning, should cleaning be necessary. A printed wiring assembly 52 which supports much of the instrument 20's optics also includes carbon pads 53 for switches 34, 36.

Heater plate assembly 50 includes leads 50-1 — 50-6. A heater element 56 is formed on a surface of a thin, translucent ceramic heater plate 58. Access is gained through lid 32 to the top surface of heater plate 58 to permit cleaning of this surface. A thermal fuse 60 is mounted on the heater plate 58 in series with the heater element 56. Leads 50-1 and 50-6 are coupled to the opposite ends of the series combination of the heater element 56 and thermal fuse 60. A chip thermistor 62 is coupled across leads 50-2 and 50-3. The anode of an 880 urn LED 64 is coupled to lead 50-5, and its cathode is coupled to lead 50-4. LED 64 is mounted with its active, light emitting region facing away from heater plate 58. Thermistor 62 and LED 64 are covered by a drop 65 of translucent, titanium dioxide-filled epoxy. The active region of LED 64 is thermally insulated from heater element 56 in this construction. A diffuse uniform light from LED 64 passes through heater plate 58 for detection by the light detection apparatus.

The coagulation sensing mechanism is thus transmission of light through an active region of strips 21, rather than reflection as in prior instruments of this general type. Also, the determination whether a sample applied to a strip 21 is blood or a control solution is made using a light transmission measurement, rather than by timing the flow of the sample between two points on the strip 21, as was done in prior instruments of this general type. Thermal insulation of the active region of LED 64 from heater element 56 reduces the temperature variation experienced by the LED 64, thereby reducing the thermally induced variation in the light output of the LED 64. This construction also results in increased light output, which provides reduced ambient light interference and greater signal to noise ratio, and reduces the criticality of the selection of LEDs 64 for sufficient light output. Assembly 52 includes a twelve-terminal connector 202 (Fig. 7a) having terminals 202-1 - 202-12, respectively. Terminals 202-1 - 202-6, 202-11 and 202-12 form the system START -. START +, FILL +, FILL -, ASSAY, BARCODE, ON/OFF BUTton and MEMory BUTton terminals, respectively. The ON/OFF BUT terminal 202-11 is coupled to one terminal of the momentary pushbutton on/off switch 34, the other terminal of which is coupled to the AnalogGrouND. The MEM BUT terminal 202-12 is coupled to one terminal of the momentary pushbutton memory switch 36, the other terminal of which is coupled to the AGND. Terminals 202-7 and -9 are coupled to the AGND. Terminal 202-8 is coupled to the +5VDC VCC supply. Terminal 202-10 is coupled to the -5VDC notVEE supply. Parallel lOμF and .01 μF capacitors are coupled between each of terminals 202-8 and 202-10 and AGND. An on-board notVDD=notVEE/2 supply (Fig. 7d) includes a 14 KΩ resistor between notVDD and notVEE, a .01 μF capacitor between notVDD and AGND, and a zener diode 208, the anode of which is coupled to notVDD and the cathode of which is coupled to AGND. Zener diode 208 illustratively is a type

LM4040 5 V shunt voltage reference. The SET BUTton terminal is coupled through a 100 KΩ resistor to VCC and to one terminal of the set button 38, the other terminal of which is coupled to AGND.

Assembly 52 includes an optics housing 210 (see also Figs. 3 and 7e). Optics housing 210 houses a START LED 210- 1 , a FILL LED 210-2 and a photodiode detector 210-3. The anode of LED 210-1 is coupled to START + and its cathode is coupled to START -. The anode of LED 210-2 is coupled to FILL + and its cathode is coupled to FILL -. The anode of detector 210-3 is coupled to notVDD and its cathode is coupled through a parallel RC circuit including a 499 KΩ, 50 ppm coefficient of thermal variation resistor and a 560 pF capacitor to the ASSAY terminal. notVDD is also coupled to the non-inverting (+) input terminal of a differential amplifier 214. The cathode of detector 210-3 is also coupled to the inverting (-) input terminal of amplifier 214. The output terminal of amplifier 214 forms the ASSAY terminal. LEDs 210-1 and -2 illustratively are type SFH405 LEDs. Detector 210-3 illustratively is a type BPW34F photodiode. Amplifier 214 illustratively is half of a type LMC662 dual differential amplifier. The anodes of eight photodiodes 218-1 — 218-8 mounted on assembly 52 are coupled to AGND. The cathodes of diodes 218-1 — 218-8 are coupled to the - input terminal of a differential amplifier 220. AGND is coupled to the + input terminal of amplifier 220. The output terminal of amplifier 220 forms the system BARCODE terminal. The output terminal of amplifier 220 is coupled through a parallel RC circuit including a 1.5 MΩ, 50 ppm coefficient of thermal variation resistor and a 560 pF capacitor to its - input terminal. Diodes 218-1 — 218-8 illustratively are type PP1101 W photodiodes. Amplifier 220 illustratively is also half of a type LMC662 dual differential amplifier. Photodiodes 218-1 — 218-8 are sequentially illuminated or not illuminated, and thereby rendered conductive or remain nonconductive, by the reflection or absorption from respective areas of the strip 21 owing to the presence or absence of code bars on the respective areas of the strips 21. LEDs 222-1 --222-8 (Fig. 7f) are sequentially excited to provide the illuminating radiation. The cathode of each LED 222-1 — 222-8 is coupled to the drain terminal of a respective FET 224-1 -- 224-8. The anode of diode 222-1 is coupled to the cathode of an LED 226 in an optical isolator 228. The collector of a light sensitive transistor 230 in optical isolator 228 is coupled through a 100 KΩ resistor to VCC. The collector of LST 230 forms the system LID 32 CLOSED terminal. The anode of LED 226 is coupled through a 75 Ω resistor to VCC. The anodes of LEDs 222-2 -222-8 are coupled through a series 200 Ω resistor to the drain terminal of an FET 236. The source of FET 236 is coupled to VCC. The gate of FET 236 is coupled through a 10 KΩ resistor to the system notBARCODE ConTRoL B terminal. The system notBARCODE CTRL B terminal is also coupled through a 100 KΩ resistor to VCC. The system notBARCODE CTRL B terminal is also coupled to the drain terminal of an FET 238, the source of which is coupled to AGND, and the gate of which is coupled through a 10 KΩ resistor to the system BARCODE CTRL terminal. The system BARCODE CTRL terminal is coupled to AGND through a 100 KΩ resistor. LEDs 222-1 - 222-8 are controlled by respective FETs 224-1 — 224-8. The source terminals of all of FETs 224-1 ~ 224-8 are coupled to the system ReTurn GrouND. The system BarCodeLED 0 ~ BCL 7 terminals, respectively, are coupled through respective 10 KΩ resistors to the gate terminals of respective FETs 224-1 - 224-8. The system BCL 0 ~ BCL 7 terminals are also coupled through respective 100 KΩ resistors to RT GND. LEDs 222-1 - 222-8 illustratively are type BR1102W LEDs. FETs 224-1 - 224-8 and 238 illustratively are type BSS138 FETs. FET 236 illustratively is a type BSS84 FET. Isolator 228 illustratively is a type GP1S33 optical isolator. Referring to Fig. 7h, START LED 210- 1 is controlled by a circuit 240 including a differential amplifier 242 and an FET 244. A 10 KΩ resistor is coupled between VCC and the system notSTART ConTRoL terminal. notSTART CTRL is coupled to the anode of a diode, the cathode of which is coupled to the - input terminal of amplifier 242. The + terminal of amplifier 242 is coupled to the system SCALED VREFerence terminal. The output of amplifier is coupled through a 10 KΩ resistor to the gate of FET 244. The drain of FET 244 is coupled to START -. The source of FET 244 is coupled through a 60.4 Ω resistor to AGND and through a 100 KΩ feedback resistor to the - input terminal of amplifier 242. Amplifier 242 illustratively is a type LMV358 amplifier. FET 244 illustratively is a type BSS138 FET.

Referring to Fig. 7j, FILL LED 210-2 is controlled by a circuit 246 including a differential amplifier 248 and an FET 250. A 10 KΩ resistor is coupled between VCC and the system notFILL ConTRoL terminal. notFILL CTRL is coupled to the anode of a diode, the cathode of which is coupled to the - input terminal of amplifier 248. The + terminal of amplifier 248 is coupled to the system SCALED VREF terminal. The output of amplifier 248 is coupled through a 10 KΩ resistor to the gate of FET 250. The drain of FET 250 is coupled to FILL -. The source of FET 250 is coupled through a 71.5 Ω resistor to AGND and through a 100 KΩ feedback resistor to the - input terminal of amplifier 248. Amplifier 248 illustratively is a type LMV358 amplifier. FET 250 illustratively is a type BSS138 FET.

Referring to Fig. 7k, the ASSAY terminal is coupled to the + input terminals of two differential amplifiers 252, 254 in a main detector interface circuit 256. Amplifiers 252, 254 are configured as unity gain buffers. The output of amplifier 254 forms the system ASSAY DC terminal. The output of amplifier 252 is coupled to a bandpass filter 257 having a passband of from 0.83 Hz to 22.4 Hz. The output of bandpass filter 257 is coupled to a differential amplifier 258, the output of which forms the system ASSAY AC terminal. Bandpass filter 257 includes a series .1 μF input capacitor, parallel 3300 pF capacitor 260 and 1.5 MΩ resistor 262 to VREF, and a series RC circuit including 100 KΩ resistors 264 and 266 and a .056 μF capacitor 268 to VREF. The common terminal of resistor 266 and capacitor 268 is coupled to the + input terminal of amplifier 258. The ASSAY AC output of amplifier 258 is coupled through series 100 KΩ resistor 270 and 20 KΩ resistor 272 to VREF, and through series 2 MΩ resistor 274 and 221 KΩ resistor 276 to VREF. The common terminal of resistors 264, 266 is coupled through a .056 μF capacitor to the common terminal of resistors 270, 272. The common terminal of resistors 274, 276 is coupled to the - input terminal of amplifier 258. Amplifiers 252, 254 illustratively are each part of a type LT1112 amplifier IC. Amplifier 258 illustratively is a type LMC6482 amplifier.

Referring to Figs. 4, 5 and 7H, a sample detector circuit 282 includes an optical assembly 284 including an LED 280 and a photodiode 286. The anode and cathode of LED 280 are coupled to the system SAMPLE + and SAMPLE - terminals, respectively. The cathode of diode 286 is coupled to VCC. The anode of diode 286 is coupled to ground through a 20 KΩ resistor and through a .001 μF capacitor to the - input terminal of a differential amplifier 290. The + input terminal of amplifier 290 is coupled to AGND. The output of amplifier 290 is coupled through a parallel RC feedback circuit including a 200 KΩ resistor and a 39 pF capacitor to its - input terminal. The output of amplifier 290 is also coupled through a 4700 pF capacitor to the + input terminal of a differential amplifier 292. The + input terminal of amplifier 292 is also coupled through a 15 KΩ resistor to AGND. The output of amplifier 292 is coupled to the anode of a diode 294, the cathode of which forms the system SAMPLE IN terminal. SAMPLE IN is also coupled through series 1 MΩ and 20 KΩ resistors 296, 298, respectively, to AGND. The common terminal of resistors 296, 298 is coupled to the - input terminal of amplifier 292, and through a 100 KΩ resistor to the anode of a diode, the cathode of which is coupled to the output of amplifier 292. Referring to Fig. 7g, the SAMPLE IN output of circuit 282 is coupled through a 1.00 KΩ resistor to the + input terminal of a sample detect buffer amplifier 300. The + input terminal of amplifier 300 is also coupled to AGND through a .047 μF capacitor. The output of amplifier 300 forms the system SAMPLE terminal. LED 280 illustratively is a type SFH405 LED. Photodiode 286 illustratively is a type BPW34F photodiode. Amplifiers 290, 292 illustratively are each part of a type LT1112 amplifier IC. Amplifier 300 illustratively is a type LMC6482 amplifier.

Referring to Fig. 7m, the signals appearing at the ASSAY DC, ASSAY AC, BARCODE and SAMPLE terminals are analog-to-digital (A/D) converted in a Δ - Σ or Σ - Δ A/D converter 306, illustratively a type ADS 1213 16-bit A/D converter. The use of this type of A D converter, rather than a dual slope A/D converter, reduces the required μP control overhead, increasing the time available for the instrument 20's system controller 310 (Figs. 7n-7p) to handle other functions. The ASSAY AC, BARCODE and SAMPLE terminals are coupled through respective 475 Ω resistors to the AIN2P, AIN3P and AIN4P terminals, respectively of A/D converter 306. The ASSAY DC terminal is coupled through a 4.75 KΩ resistor to the AIN1P terminal of converter 306. The AIN1P, AIN2P, AIN3P and AIN4P terminals are also coupled through respective 39 pF capacitors to AGND. The AIN1P terminal is also coupled through a 4.75 KΩ resistor to the system VBIAS supply. The AIN1N, AIN2N,

AIN3N, AIN4N, REFerence IN and REF OUT terminals of converter 306 are coupled to VREF. The system notAD SYNC, notAD READY, AD IN, VBIAS, AD CLocK, and AD FREQuency terminals are coupled to the notDSYNC, not DReaDY, VBIAS, SDIO, SCLocK and XIN terminals, respectively, of converter 306. The instrument 20 is controlled by system controller 310. The illustrative controller is an NEC μPD78P064 microcomputer. Controller 310 terminals P30/TO0 (Fig. 7n), P31/TO1, P32/TO2 (through a 100 Ω resistor), P33/TI1 (through a 100 Ω resistor), P34/TI2 (through a 100 Ω resistor), P25/SI0/SB0 (through a 100 Ω resistor), P26/SO0/SB1 (through a 100 Ω resistor), P27/notSCK0 (through a 100 Ω resistor), P70/SI2/RXD and P02/INTP2 (through a 100 Ω resistor), P71/SO2/TXD, P72/notSCK2/ASCK, P10/ANI0 (through a 475 Ω resistor), P11/ANI1 (Fig. 7o), P12/ANI2, P13/ANI3, P14/ANI4 (through a 100 Ω resistor), P15/ANI5, P16/ANI6 (through a 100 Ω resistor), P17/ANI7 (through a 100 Ω resistor), P00/INTP0/TIO0, P01/INTP1/TIO1, P03/INTP3, P04/INTP4, P05/TNTP5, P80/S39, P81/S38, P82/S37, P83/S36, P84/S35, P85/S34 (Fig. 7p), P86/S33, P87/S32, P90/S31, P91/S30, P92/S29, P93/S28, P94/S27, P95/S26, P96/S25, P97/S24, P100, P101, P102, P103, P110, Pi l l, P112, P113, P114, P115, P116 and Pl 17, respectively, form the system HEATER ConTRoL, notMAGNET ConTRoL, 12 CLocK, I2DATA, LID CLOSED, CodeRom Chip Select, CR IN/OUT, CR CLocK, RX232, TX232, notPower ManaGeR, BARCODE, VBAT2, HEATER TEMPerature, VADAPT5, notAD SYNC, BARCODE CTRL, AD IN, AD CLK, notAD READY, notERROR, ON/OFF BUT, SET BUT, MEM BUT, SS39, SS38, SS37, SS36, SS35, SS34, SS33, SS32, SS31, SS30, SS29, SS28, SS27, SS26, SS25, SS24, BCLO, VBAT + BCL1, TARGET + BCL2, BCL3 + CC1, BCL4 + CC2, BCL5 + CC4, BCL6 + CC8, BCL7 + CC16, notSTART CTRL, notMAIN CTRL, notSAMPLE CTRL, and notFILL CTRL terminals, respectively. Controller 310 terminals SO - S 16 (Fig. 7n), S 17 - S23 (Fig. 7o),

COM0 - COM3, P35/PCL (through a 100 Ω resistor - Fig. 7p), P36/BUZ and P37, respectively, form the system SSO - SS23, COM0 - COM3, AD FREQ, BUZZER and SWITCHER ConTRoL terminals, respectively. A 4.9152 MHz clock is coupled across terminals XI and X2 of controller 310 (Fig. 7p). A 32.768 KHz clock is coupled across terminals XT1/P07 and XT2 of controller 310. A reset voltage regulator circuit including a voltage detector IC 312 is coupled to the notRESET terminal of controller 310. IC 312 illustratively is a type S-80826ANUP 2.6 V detector IC. Referring to Fig. 7o, a series string of a 31.6 KΩ resistor 314, a 66.5 KΩ resistor 316, a 66.5 KΩ resistor 318 and a 66.5 KΩ resistor 320 is coupled between the BIAS terminal of controller 310 and AGND. The common terminal of resistors 314 and 316 is coupled to the VLC0 terminal of controller 310. The common terminal of resistors 316 and 318 is coupled to the VLC1 terminal of controller 310. The common terminal of resistors 318 and 320 is coupled to the VLC2 terminal of controller 310. LCD 30 (Figs. 1, 6 and 7q) has COM1A - COM4A terminals and

COMIB ~ COM4B terminals, respectively, joined and coupled to the instrument 20's COM0 - COM3 terminals, respectively. LCD 30 has its SI - S8 terminals coupled to the instrument 20's SSO -- SS7 terminals, respectively, and its S9 ~ S40 terminals coupled to the instrument 20's SS8 — SS39 terminals, respectively. The sample LED 280 is controlled by a control circuit 324 (Fig. 7i) including a differential amplifier 326 and an FET 328. A 10 KΩ resistor is coupled between VCC and the system notSAMPLE ConTRoL terminal. notSAMPLE CTRL is coupled to the anode of a diode, the cathode of which is coupled to the - input terminal of amplifier 326. The + terminal of amplifier 326 is coupled to the system SCALED VREF terminal. The output of amplifier 326 is coupled through a 10 KΩ resistor to the gate of FET 328. The drain of FET 328 is coupled to SAMPLE -. The source of FET 328 is coupled through a 124 Ω resistor to AGND and through a 100 KΩ feedback resistor to the - input terminal of amplifier 326. Amplifier 326 illustratively is a type LMV358 amplifier. FET 328 illustratively is a type BSS138 FET.

The main LED 64 is controlled by a control circuit 330 (Fig. 7r) including a differential amplifier 332 and an FET 334. A 10 KΩ resistor is coupled between VCC and the system notMAIN ConTRoL terminal. notMAIN CTRL is coupled to the anode of a diode, the cathode of which is coupled to the - input terminal of amplifier 332. The + terminal of amplifier 332 is coupled to the system SCALED VREF terminal. The output of amplifier 332 is coupled through a 10 KΩ resistor to the gate of FET 334. The drain of FET 334 is coupled to MAIN -. The source of FET 334 is coupled through a 309 Ω resistor to AGND and through a 100 KΩ feedback resistor to the - input terminal of amplifier 332. Amplifier 332 illustratively is a type LMV358 amplifier. FET 334 illustratively is a type BSS138 FET. Prior instruments of the general type of instrument 20 conducted a timed assay, illustratively 75 seconds in length. Instrument 20 conducts an end of reaction assay, determining when the light modulation drops below an established threshold to determine when coagulation has occurred. The instrument 20 does, however, establish an assay time limit of, illustratively, 75 seconds. This assay strategy and algorithm promote battery life. The strips 21 are provided with target areas 340 for the application of blood or control at the beginning of a test. The target area 340 is indicated when a strip 21 is in the instrument 20 by a yellow LED 342. The strips 21 are designed so that LED 342 shines through a clear target area of a strip 21 when the strip 21 is inserted into the instrument 20 in the proper orientation for conducting a test, illuminating the target area for the user's convenience in applying a drop of blood or control to the strip 21. LED 342 is controlled by a control circuit 344 (Fig. 7t) including an FET 346. A 10 KΩ resistor is coupled between the system TARGET + BCL2 terminal and the gate of FET 346. notBARCODE CTRL B is coupled to the cathode of a diode, the anode of which is coupled to the gate of FET 346. The drain of FET 346 is coupled through a 200 Ω resistor to the cathode of LED 342. The anode of LED 342 is coupled to the system VUNREGulated voltage source. The source of FET 346 is coupled to AGND. FET 346 illustratively is a type BSS138 FET. LED 342 illustratively is a type LYA676-R LED.

The electromagnet 44 is driven from a current source 350 (Fig. 7v) including a differential amplifier 352 and a power FET 354. The notMAGNET ConTRoL terminal is coupled to the anode of a diode 356, the cathode of which is coupled to the - input terminal of amplifier 352. The anode of diode 356 is also coupled through a 10 KΩ resistor to VCC. The output of amplifier 352 is coupled through a 10 KΩ resistor to the gate of FET 354. The source of FET 354 is coupled through a 1Ω, 100 ppm resistance to the system ReTurn GrouND, and through a 10 KΩ feedback resistor to the - input terminal of amplifier 352. The drain of FET 354 is coupled to one terminal 44-1 of the electromagnet 44. The other terminal 44-2 of the electromagnet 44 is coupled to VUNREGulated. A snubbing and damping circuit including the series combination of a 39 Ω resistor and a .1 μF capacitor, in parallel with a diode is coupled across terminals 44-1 and 44-2. A series resistive voltage divider including a 100 KΩ resistor 356 and a 9.09 KΩ resistor 358 is coupled across VREFerence and RT GND. The junction of resistors 356 and 358 is coupled to the + terminal of amplifier 352. This voltage divider establishes the voltage on the +terminal of amplifier at .083 VREF. Differential amplifier 352 illustratively is a type LMC7101 differential amplifier. FET 354 illustratively is a type SI3442DV FET. A control circuit 360 (Fig. 7w) for the heater plate assembly 50 includes a differential amplifier 362 and a power FET 364. A series resistive voltage divider including a 59.0 KΩ, 25 ppm resistor 366 and a 20 KΩ, 25 ppm resistor 368 is coupled between VREF and AGND. The junction of resistors 366 and 368 is coupled to the + input terminal of amplifier 362. The - input terminal of amplifier 362 is coupled through the series combination of a 51.1 KΩ, 25 ppm resistor 370 and a 20 KΩ, 25 ppm resistor 372 to VREF. The output terminal of amplifier 362 forms the instrument 20's HEATER TEMPerature terminal. The output terminal of amplifier 362 is coupled through a parallel RC feedback circuit including a 1 MΩ, 50 ppm resistor and a 220 pF capacitor to its - input terminal. The junction of resistors 370 and 372 is coupled to terminal 50-2 of the heater plate assembly 50.

The heater element 56 is driven from the drain terminal of FET 364, which is coupled to terminal 50-1 of the heater plate assembly 50. The gate of FET 364 is coupled through series 10 KΩ resistor 374 and 100 KΩ resistor 376 to AGND. The junction of resistors 374, 376 is coupled to the instrument 20's HEATER ConTRoL terminal. The source of FET 364 is coupled to ReTurn GrouND. Terminal 50-6 of the heater plate assembly 50 is coupled to VUNREG. Rather than having a potentiometer in the heater control circuit 360 and adjusting that potentiometer to 39 °C during final setup of the instrument 20, the instrument 20 provides an algorithm for controlling the heater element 56. The algorithm includes a constant which is written to the instrument 20s EEPROM during final setup of the instrument 20. This constant is loaded into the instrument 20s EEPROM through port 380. Thus, the instrument 20 does not need to be kept open for calibration, but rather, can be finally assembled prior to calibration. The method also permits the instrument 20 to bring the heater plate 50 more rapidly into its control range than a linear voltage regulator was capable of doing. Additionally, this method is more efficient and promotes battery life, permitting a reduction in the number of dry cells required to operate the instrument 20 for a reasonable length of time from, for example, six, to, for example, four.

Terminals 50-4 and 50-5 are coupled to the instrument 20's MAIN - and MAIN + terminals, respectively. Terminal 50-3 is coupled to AGND. Differential amplifier 362 illustratively is a type LMC7101 differential amplifier. FET 364 illustratively is a type SI3442DV FET. The instrument 20 includes a serial port 380 (Fig. 7x) having terminals

380-1, 380-2 and 380-3. Terminal 380-1 is coupled through a 10 KΩ resistor to the base of a transistor 382. The collector of transistor 382 is coupled through a 10 KΩ resistor to the instrument 20's VUP supply. The collector of transistor 382 forms the instrument 20's RX232 terminal. The base of transistor 382 is coupled through a parallel circuit including a 100 KΩ resistor and a .001 μF capacitor to AGND. The instrument 20's TX232 terminal is coupled through a 10 KΩ resistor to the base of a transistor 384. The emitter of transistor 384 is coupled to the VCC supply. The base of transistor 384 is coupled through a 10 KΩ resistor to the VCC supply. The collector of transistor 384 is coupled through a 10 KΩ resistor to the notVEE supply. The collector of transistor 384 is also coupled to the bases of two transistors 386, 388. The collector of transistor 386 is coupled to VCC and its emitter is coupled to the emitter of transistor 388. The collector of transistor 388 is coupled to notVEE. The joined emitters of transistors 386, 388 are coupled through a 100 Ω resistor to terminal 380-2, and through a .001 μF capacitor to AGND. Transistors 382 and 386 illustratively are type 2N3904 transistors. Transistors 384 and 388 illustratively are type MMBT3906 transistors. The instrument 20 also includes an I²C interface 390 (Fig. 7y).

Interface 390 includes a digital thermometer IC 392 of the general type discussed in PCT/US98/25863, the disclosure of which is incorporated herein by reference. An illustrative digital thermometer is the LM75 digital temperature sensor IC. Instrument 20's 12 CLocK and 12 DATA terminals are coupled to the SCL and SDA terminals, respectively, of the digital thermometer 392. The SCL and SDA terminals of digital thermometer 392 are also coupled to the SCL and SDA terminals, respectively, of a serial EEPROM IC 394. Serial EEPROM 394 illustratively is a type 24C128 serial EEPROM IC. The WP, NC, A0, Al and GND terminals of serial EEPROM 394 are coupled to AGND. Power is supplied to ICs 392, 394 from instrument 20's VUP supply through a FET 396. FET 396 illustratively is a type BSS84 FET. The instrument 20's notPower ManaGeR terminal is coupled to the gate of FET 396. The drain of FET 396 is coupled to VUP. The source of FET 396 is coupled to the +VS and Al terminals of IC 392, to the VCC terminal of IC 394, and through respective 10 KΩ resistors to instrument 20's 12 CLocK and 12 DATA terminals. Instrument 20 also includes a port 400 (Fig. 7z) for receiving a key which carries a ROM containing, inter alia, lot-specific parameters for the strips 21 currently in use in the instrument 20. Port 400 includes terminals 400-1 — 400-8. Terminals 400-1 — 400-3 are coupled through respective 100 Ω resistors to the instrument 20's CodeROM ChipSelect, CodeROM CLocK, CodeROM INput/OUTput terminals, respectively. Terminal 400-4 is coupled to terminal 400-3. Terminal 400-5 is coupled to AGND. VCC to terminal 400-8 is controlled from the instrument 20's VBAT + BCL1 terminal through a transistor 401 and a 100 Ω resistor 403. The emitter of transistor 401 is coupled to VCC. Its collector is coupled through resistor 403 to terminal 400-8. Its base is coupled through a 10 K Ω resistor to the drain terminal of an FET 405. The drain of FET 405 is also coupled through a 100 K Ω resistor to VCC. The source of FET 405 is coupled to AGND. The gate of FET 405 is coupled through a 10 K Ω resistor to VBAT + BCL 1. The purposes and functions of such code ROM keys are explained further in U.S. Patent No. 5,053,199. The code ROM on the key which port 400 is adapted to receive illustratively is a type NMC93C56 or C66 ROM. Transistor 401 illustratively is a type MMBT3906 transistor. FET 405 illustratively is a type BSS138 FET. Instrument 20 includes an audio beeper driver circuit 404 (Fig. 7aa) for driving a piezoelectric beeper 405 to produce sounds audible to the user of instrument 20 under certain circumstances, such as on depression of a button 34, 36, 38. The beeper driver circuit 404 includes driver transistors 406 and 408. The collector of transistor 406 is coupled to an output terminal 410-1 of circuit 404. The collector of transistor 406 is also coupled through a 2 KΩ resistor to VUNREG. The emitter of transistor 406 is coupled to AGND. The base of transistor 406 is coupled through a 10 KΩ resistor to the instrument 20's BUZZER terminal. The BUZZER terminal is also coupled through a 10 KΩ resistor to AGND. The collector of transistor 408 is coupled to an output terminal 410-2 of circuit 404. The base of transistor 408 is coupled through a 10 KΩ resistor to the collector of transistor 406. The emitter of transistor 408 is coupled to VUNREG. Terminal 410-2 is coupled through a 2 KΩ resistor to AGND. The piezoelectric beeper 405 is coupled across terminals 410-1 and 410-2.

Because the characteristics, for example, light output, of LEDs 64 can vary considerably from LED to LED, and because these differences in light output can affect the performance of the instrument 20, in the past, LEDs which performed the function of LEDs 64 had to be evaluated before they were incorporated into instruments of the general type of instrument 20. Other instrument components had to be selected to complement the light output characteristics of the LEDs. Frequently, LEDs were rejected as outputting too much or too little light to provide a high likelihood of satisfactory instrument performance. These factors complicated instrument assembly, among other things. The instrument 20 of the present invention takes another approach to this problem, providing the final instrument 20 setup technician the flexibility to choose the supply voltages for LEDs 64. Specifically, and with reference to Fig. 7bb, a 14.7 KΩ resistor 420 forms a voltage divider with an 11 KΩ resistor 422-1 selected by energizing an FET 424-1 using the BCL7 + CCl 6 terminal, a voltage divider with a 20 KΩ resistor 422-2 selected by energizing an FET 424-2 using the BCL6 + CC8 terminal, a voltage divider with a 44.2 KΩ resistor 422- 3 selected by energizing an FET 424-3 using the BCL5 + CC4 terminal, a voltage divider with an 88.7 KΩ resistor 422-4 selected by energizing an FET 424-4 using the BCL4 + CC2 terminal, and a voltage divider with a 191 KΩ resistor 422-5 selected by energizing an FET 424-5 using the BCL3 + CCl terminal. Selective energization of one of FETs 424-1, 424-2, 424-3, 424-4 and 424-5 provides a SCALED VREF which is 42.8%, 57.6%, 75%, 85.8% and 92.8%, respectively, of VREF. Additionally, it should be understood that energization of various combinations of these FETs 424-1, 424-2, 424-3, 424-4 and 424-5 can provide additional relationships between VREF and SCALED VREF, should such additional voltages be desirable. The gate of each of FETs 424-1, 424-2, 424-3, 424-4 and 424-5 is coupled to its respective signal source BCL7 + CCl 6, BCL6 + CC8, BCL5 + CC4, BCL4 + CC2 and BCL3 + CCl through a respective 10 KΩ resistor. The sources of FETs 424-1, 424-2, 424-3, 424-4 and 424-5 are coupled to AGND. The drain of each of FETs 424-1, 424-2, 424-3, 424-4 and 424-5 is coupled to one terminal of its respective 11 KΩ, 20 KΩ, 44.2 KΩ, 88.7 KΩ and 191 KΩ resistor. The other terminals of these 11 KΩ, 20 KΩ, 44.2 KΩ, 88.7 KΩ and 191 KΩ resistors are coupled through resistor 420 to VREF. The common terminal of resistor 420 and resistors 422-1 ~ 422-5 forms the SCALED VREF terminal. Power for the instrument 20 is supplied from several supplies including a VUNREGulated pulsewidth modulated, switching power supply 430 (Fig. 7cc). Supply 430 includes a pair of supply terminals 432, 434 across which four 1.5 V nominal, AA size dry cells maintain a VBATtery voltage < 6.4 VDC. 33 μF non- polar and .1 μF capacitors are coupled in parallel across terminals 432, 434. A 100 KΩ resistor 436 is coupled between terminal 432 and the drain of an FET 438. The source of FET 438 is coupled to AGND. The gate of FET 438 is coupled through a 10 KΩ resistor to the instrument 20's SWITCHER ConTRoL terminal. The SWITCHER CTRL terminal is also coupled to AGND through a 100 KΩ resistor. In the event a DC adapter is being used to power the instrument 20, FET 438 is held off by a transistor 440, the collector of which is coupled to the gate of FET 438, the emitter of which is coupled to AGND, and the base of which is coupled through alOKΩ resistor to the cathode of a 7.5 V zener diode 442, the anode of which is coupled to the instrument 20's VADAPTer terminal. The parallel combination of a 2 KΩ resistor and a .1 μF capacitor is coupled between the cathode of zener diode 442 and AGND. The drain of FET 438 is coupled through respective 10 KΩ resistors to the gates of two power FETs 444, 446. The source of FET 444 is coupled to terminal 432. The drain of FET 444 is coupled to the drain of FET 446. The source of FET 446 is coupled through a 22 μH inductor 448, a Schottky diode 450, a ferrite bead 452 and a 10 μH inductor 454 in series to the instrument 20's VUNREG terminal where circuit 430 provides unregulated 6.4 VDC for the instrument 20. Parallel 100 μF and .1 μF capacitors are coupled between VUNREG and AGND. Parallel 100 μF, 100 μF and .1 μF capacitors are coupled between the junction of inductors 452 and 454 and AGND. Parallel 100 μF, 100 μF and .1 μF capacitors are coupled between the junction of FET 446 and inductor 448 and RT GND.

A switchmode voltage regulator IC 456 has its PGND terminal coupled to RT GND, its SW terminal coupled to the junction of inductor 448 and the anode of Schottky diode 450, its VIN terminal coupled through a 2 Ω resistor to the source of FET 446, its SHutDowN terminal coupled to AGND, its IT terminal coupled through a 3.3 KΩ resistor to AGND, its GND terminal coupled to AGND, its VC terminal coupled through a series RC circuit including a 3.3 KΩ resistor and a .1 μF capacitor to AGND, and its SENSE/FeedBack terminal coupled through a 422 KΩ resistor to the junction of inductors 452, 454. The VIN terminal is also coupled through a .1 μF capacitor to AGND, the SW terminal is coupled through a series RC circuit including a 220 pF capacitor and a 39 Ω resistor to AGND, and the SENSE/FB terminal is coupled through a parallel RC circuit including a 220 pF capacitor and a 100 KΩ resistor to AGND. FET 438 illustratively is a type BSS138 FET, transistor 440 illustratively is a type 2N3904 transistor, FETs 444, 446 illustratively are type

SI6963DQ FETs, zener diode 442 illustratively is a type BZX84C7V5 zener diode, Schottky diode 450 illustratively is a type 10BQ040 Schottky diode, and voltage regulator IC 456 illustratively is a type LT1302 IC.

Instrument 20 also includes a VUNREGulated linear supply 460 (Fig. 7dd) which is powered from an AC adapter, for example, a 10 VDC, 750 mA adapter (not shown), through an adapter port 462 including terminals 462-1 and 462-2. The series combination of a half ampere resettable fuse, a ferrite bead, a winding 464-1 of a common mode noise filter 464 and a diode 466 are coupled between terminal 462-1 and the instrument 20's VADAPTer terminal. The series combination of a ferrite bead and the other winding 464-2 of filter 464 is coupled between terminal 462-2 and AGND. The parallel combination of a .1 μF capacitor and back-to-back 18 VDC zener diodes 463 is coupled between the junction of winding 464-1 and the anode of diode 466 and AGND. A 10 μF capacitor is coupled between VADAPT, the cathode of diode 466, and AGND.

VADAPT is coupled to the INput terminal of a voltage regulator IC 468. The ON-OFF and GrouND terminals of voltage regulator 468 are coupled to AGND. The OUTput terminal of voltage regulator 468 is coupled through a series resistive voltage divider including a 9.75 KΩ resistor 470 and a 2KΩ resistor 472 to AGND to provide at the ADJust terminal of voltage regulator 468 a nominal 1.22533 VDC regulator 468 programming signal. The OUT terminal of voltage regulator 468 is also coupled to the anode of a diode 474, the cathode of which forms the VUNREG terminal of instrument 20. The OUT terminal of regulator 468 is coupled through the parallel combination of a 470 μF capacitor, a 470 μF capacitor, a 100 μF capacitor, and a .1 μF capacitor to AGND. Zener diodes 463 illustratively are a type SMBJ18C package, voltage regulator 468 illustratively is a type LM2941C voltage regulator, and filter 464 illustratively is a type M-521 CT chip filter.

Power supplies 430 and 460 incorporate reverse polarity protection, proper polarity, out of voltage range protection, both high and low, low current supply protection, AC versus DC adapter protection, electrical fast transient protection and electromagnetic interference protection. Additionally, when the instrument 20 is turned on, firmware in the instrument 20 places a load across the power supply to determine that it is operating properly. A 3 VDC backup power supply 480 (Fig. 7ee) includes a diode 482 coupled between the instrument 20's VBAT terminal and an INput terminal of a voltage regulator IC 484. The OUTput terminal of voltage regulator 484 is coupled to the VS terminal of a voltage monitor and switching IC 486. The OUT terminal of voltage regulator 484 is also coupled to the source of an FET 488, the drain of which is coupled to the drain of an FET 490. The source of FET 490 forms the instrument 20's VUninterruptedPower supply terminal. IC 486 monitors the instrument 20's VCC voltage at its terminal VP. IC 486's notP terminal is coupled through a 3.3 KΩ resistor to the base of a transistor 492. The emitter of transistor 492 is coupled to VCC, and its collector is coupled through a 100 Ω resistor 494 and a .047 μF capacitor 496 to AGND. As long as VCC is present, capacitor 496 is charged from VCC through the emitter-collector path of transistor 492 and resistor 494. If VCC should disappear, capacitor 496 discharges through a diode 498 whose anode is coupled to the junction of resistor 494 and capacitor 496 and whose cathode is coupled to VUP, to maintain the instrument 20's volatile memory, and for whatever other functions require uninterrupted power. A 100 KΩ resistor is coupled between the notP terminal of IC 486 and the collector of transistor 492. Drive for the gates of FETs 488 and 490 is provided from the notS terminal of IC 486 through respective 10 KΩ resistors. A 1 MΩ resistor is coupled between the source of FET 490 and notS. Parallel 10 μF and .1 μF capacitors are coupled between the IN terminal of IC 484 and AGND, and between the OUT terminal of IC 484 and AGND. IC 484 illustratively is a type 78LC30 IC, IC 486 illustratively is a type ICL7673 IC, FETs 488 and 490 illustratively are type BSS84 FETs, and transistor 492 illustratively is a type MMBT3906 transistor. Backup power supply 480 provides a minimum of 10 minutes or so of protection for the instrument 20's volatile memory, for example, date and time, when, for example, the battteries are removed for replacement or the like.

The instrument 20's VCC supply 510 (Fig. 7ff) includes a voltage regulator IC 512 whose INput terminal is coupled to VUNREG, and whose OUTput terminal forms instrument 20's VCC terminal. The ERROR terminal of IC 512 is coupled through a 100 Ω resistor to instrument 20's notERROR terminal. Parallel 10 μF and .1 μF capacitors are coupled between the IN terminal of IC 512 and AGND, and between the OUT terminal of IC 512 and AGND. IC 512 illustratively is a type LP2951CM adjustable voltage regulator IC.

The instrument 20's notVEE supply (Fig. 7gg) includes a voltage regulator inverter IC 516 whose VIN terminal is coupled through a 100 μH, 10% inductor to VUNREG. NotVEE of -5 VDC appears at the VOUT terminal of IC 516. Parallel 10 μF and .1 μF capacitors are coupled between the VIN terminal of IC 516 and AGND, and between the VOUT terminal of IC 516 and AGND. A series resistive voltage divider including a 191 KΩ resistor 518 and a 66.5 KΩ resistor 520 establishes at the junction of resistors 518 and 520 a FeedBack voltage to the FB terminal of IC 516. IC 516 illustratively is a type MAX851 regulated voltage inverter IC.

Instrument 20 also includes a 0.399 VBAT supply (Fig. 7hh) including an FET 522. The gate of FET 522 is coupled through a 100 Ω resistor to the instrument 20's VBAT + BCL1 terminal. Its drain is coupled through a 66.5 KΩ resistor to VBAT, and its source is coupled through a 44.2 KΩ resistor to AGND. When FET 522 is on, 0.399 VBAT appears on its source terminal. FET 522 illustratively is a type BSS138 FET.

Claims

CLAIMS:

1. An instrument for determining a characteristic of a sample of a biological fluid or a control, the instrument including a first source for providing radiation for transmission through a region of the sample, a second source for providing heat for maintaining the sample at a desired temperature, the second source including a plate having first and second generally opposite sides, the plate including a material which is not opaque, the first source being mounted on the first side of the plate and the sample being disposed on the second side of the plate during the determination of the characteristic, with the radiation passing through the non-opaque material and into the sample and then being detected in order to determine the characteristic.

2. The apparatus of claim 1 wherein the first source includes a light emitting diode (LED) mounted with its light emitting region facing away from the first side, and a reflective material for reflecting light back toward the first side.

3. The apparatus of claim 2 wherein the first source includes an LED which emits infrared radiation.

4. The apparatus of claim 1 wherein the second source includes a heater element provided on the first side of the plate.

5. The apparatus of claim 4 wherein the heater element is thermally insulated from the first source to reduce thermal variation of the radiation output from the first source.

6. The apparatus of claim 4 further including a controller for controlling the heater element, the controller including a temperature sensing device for sensing the temperature of the plate.

7. The apparatus of claim 6 wherein the controller controls the heat source according to an algorithm including a parameter which varies from instrument to instrument, the apparatus further including a port through which the parameter can be entered into the controller to control the second source.

8. The apparatus of claim 4 further including a first power supply coupled to the heater element, the first power supply including a switching power supply.

9. The apparatus of claim 8 wherein the switching power supply includes a pulsewidth modulated power supply.

10. The apparatus of claim 1 wherein the first source is one selected from among a plurality of first sources which provide different radiation output in response to the same input power, the apparatus further including a first power supply coupled to the first source, the first power supply selectively providing different levels of power to the first source in order to provide a desired radiation output.

11. The apparatus of claim 1 further including a first power supply coupled to the heater element, the first source being one selected from among a plurality of first sources which provide different radiation output in response to the same input power, the apparatus further including a second power supply coupled to the first source, the first power supply selectively providing different levels of power to the first source in order to provide a desired radiation output.

12. The apparatus of claim 10 wherein the first power supply includes a voltage divider, the voltage divider including a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements, each of the second divider elements being coupled in circuit with a respective one of the switches, each of the switches having a control input for actuating that respective switch to place its respective second divider element in circuit with the first divider element to divide a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

13. The apparatus of claim 12 wherein multiple ones of the switches can be actuated simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

14. The apparatus of claim 13 wherein the respective multiple ones of the second divider elements are placed in parallel with one another when their respective ones of the switched are actuated simultaneously.

15. An instrument for determining a characteristic of a sample of a biological fluid or a control, the instrument including a source for providing radiation for illuminating the sample in order to determine the characteristic, the source being one selected from among a plurality of sources which provide different radiation output in response to the same input power, the apparatus further including a power supply coupled to the source, the power supply selectively providing different levels of power to the source in order to provide a desired radiation output.

16. The apparatus of claim 15 wherein the power supply includes a voltage divider, the voltage divider including a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements, each of the second divider elements being coupled in circuit with a respective one of the switches, each of the switches having a control input for actuating that respective switch to place its respective second divider element in circuit with the first divider element to divide a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

17. The apparatus of claim 16 wherein multiple ones of the switches can be actuated simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

18. The apparatus of claim 17 wherein the respective multiple ones of the second divider elements are placed in parallel with one another when their respective ones of the switches are actuated simultaneously.

19. An instrument for determining a characteristic of a sample of a biological fluid or a control, the instrument including a switching power supply.

20. The apparatus of claim 19 wherein the switching power supply includes a pulsewidth modulated power supply.

21. The apparatus of claim 19 further including a source for providing heat for maintaining the sample at a desired temperature.

22. The apparatus of claim 21 further including a controller for controlling the heat source, the controller including a temperature sensing device for sensing the temperature of the heat source.

23. The apparatus of claim 20 wherein the controller controls the heat source according to an algorithm including a parameter which varies from instrument to instrument, the apparatus further including a port through which the parameter can be entered into the controller to control the heat source of the apparatus.

24. The apparatus of claim 23 wherein the port is a serial port.

25. The apparatus of claim 24 wherein the port is an RS-232 port.

26. An instrument for determining a characteristic of a sample of a biological fluid or a control, the instrument including a source for providing radiation for transmission through a region of the sample, the instrument including a detector for detecting the radiation transmitted through the sample, and a controller coupled to the detector for determining when a characteristic of the transmitted radiation drops below a threshold, and determining the characteristic based upon the time required for the transmitted radiation to drop below the threshold.

27. The apparatus of claim 26 wherein the controller measures the elapsed time that the transmitted radiation has been above the threshold, the controller establishing a maximum elapsed time, the controller determining when the elapsed time reaches the maximum elapsed time and determining the characteristic based upon the detected radiation when the elapsed time reaches the maximum elapsed time.

28. The apparatus of claim 26 wherein the controller further includes a controller for determining from the characteristic of the transmitted radiation whether the applied sample is a patient sample or whether the applied sample is a sample of a control.

29. The apparatus of claim 28 wherein the instrument determines the characteristic by combining the biological fluid or control with nontransparent ferromagnetic particles, subjecting the combination to a time varying magnetic field, and detecting the modulation of the transmittance of radiation through the combination.

30. The apparatus of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 or 29 wherein the biological fluid is blood or a blood fraction, and the characteristic of the biological fluid is a coagulation characteristic.

31. A method of determining a characteristic of a sample of a biological fluid or a control, the method including transmitting radiation through a region of the sample, maintaining the sample at a desired temperature, transmitting radiation through a region of the sample including providing a plate having first and second generally opposite sides, the plate including a material which is not opaque, transmitting radiation from the first side of the plate, placing the sample on the second side of the plate during the determination of the characteristic, and passing the radiation through the non-opaque material and into the sample and then detecting the radiation in order to determine the characteristic.

32. The method of claim 31 wherein transmitting radiation from the first side of the plate includes mounting a light emitting diode (LED) with its light emitting region facing away from the first side, and applying a reflector to the light emitting region to reflect light back toward the first side.

33. The method of claim 32 wherein transmitting radiation includes transmitting infrared radiation.

34. The method of claim 31 wherein maintaining the sample at a desired temperature includes providing a heater element on the first side of the plate.

35. The method of claim 34 wherein transmitting radiation through a region of the sample includes transmitting radiation from a first source of such radiation through a region of the sample, the method further including thermally insulating the heater element from the first source to reduce thermal variation of the radiation output from the first source.

36. The method of claim 34 further including controlling the heater element by sensing the temperature of the plate.

37. The method of claim 34 wherein controlling the heater element includes controlling the heater element according to an algorithm including a parameter which varies from instrument to instrument, the method further including providing a port through which the parameter can be entered into the algorithm.

38. The method of claim 32 further including supplying power to the heater element from a switching power supply.

39. The method of claim 38 wherein supplying power to the heater element from a switching power supply includes supplying power to the heater element from a pulsewidth modulated power supply.

40. The method of claim 31 wherein transmitting radiation from the first side of the plate includes transmitting radiation from a first source selected from among a plurality of first sources which provide different radiation output in response to the same input power, the method further including selectively providing different levels of power to the first source in order to provide a desired radiation output.

41. The method of claim 40 wherein selectively providing different levels of power to the first source includes providing a voltage divider including a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements, coupling each of the second divider elements in circuit with a respective one of the switches, providing for each of the switches a control input for actuating that respective switch to place its respective second divider element in circuit with the first divider element, and thereby dividing a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

42. The method of claim 41 wherein actuating respective switches to place their respective second divider elements in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

43. The method of claim 42 wherein actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in parallel with one another.

44. A method for determining a characteristic of a sample of a biological fluid or a control, the method including providing radiation from a source of such radiation for illuminating the sample in order to determine the characteristic, the source being one selected from among a plurality of such sources which provide different radiation output in response to the same input power, the method further including coupling a power supply selectively providing different levels of power to the radiation source, the power supply selectively providing a level of power to the radiation source in order to provide a desired radiation output from the radiation source.

45. The method of claim 44 wherein coupling a power supply selectively providing different levels of power to the radiation source includes coupling a power supply having a voltage divider including a first divider element, a plurality of second divider elements and a plurality of switches, one switch for each of the second divider elements, to the radiation source, each of the second divider elements being coupled in circuit with a respective one of the switches, the method further including actuating a respective switch to place its respective second divider element in circuit with the first divider element to divide a voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

46. The method of claim 45 wherein actuating a respective switch to place its respective second divider element in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element to divide the voltage provided to the voltage divider by an amount appropriate to provide the desired radiation output.

47. The method of claim 46 wherein actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in circuit with the first divider element includes actuating multiple ones of the switches simultaneously to place respective multiple ones of the second divider elements in parallel with one another when their respective ones of the switches are actuated simultaneously.

48. A method of operating an instrument for determining a characteristic of a sample of a biological fluid or a control, the method including providing in the instrument a switching power supply.

49. The method of claim 48 wherein providing in the instrument a switching power supply includes providing in the instrument a pulsewidth modulated power supply.

50. The method of claim 48 further including providing in the instrument a source for providing heat for maintaining the sample at a desired temperature.

51. The method of claim 50 further including providing in the instrument a controller including a temperature sensing device for sensing the temperature of the heat source for controlling the heat source.

52. The method of claim 49 wherein providing in the instrument a controller for controlling the heat source includes providing in the instrument a controller for controlling the heat source according to an algorithm including a parameter which varies from instrument to instrument, the method further including providing on the instrument a port and entering the parameter through the port.

53. The method of claim 52 wherein providing on the instrument a port includes providing on the instrument a serial port.

54. The method of claim 53 wherein providing on the instrument a port includes providing on the instrument an RS-232 port.

55. A method for determining a characteristic of a sample of a biological fluid or a control, the method including providing an instrument including a source for providing radiation for transmission through a region of the sample, providing in the instrument a detector for detecting the radiation transmitted through the sample, and providing in the instrument a controller coupled to the detector for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold.

56. The method of claim 55 wherein providing in the instrument a controller for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold includes providing a controller which measures the elapsed time that the transmitted radiation has been above the threshold, the method further including establishing a maximum elapsed time, determining when the elapsed time reaches the maximum elapsed time, and determining the characteristic based upon the detected radiation when the elapsed time reaches the maximum elapsed time.

57. The method of claim 55 wherein providing in the instrument a controller for determining the characteristic based upon the time required for the transmitted radiation to drop below a threshold includes providing a controller for determining from the characteristic of the transmitted radiation whether the applied sample is a patient sample or whether the applied sample is a sample of a control.

58. The method of claim 57 wherein providing an instrument for determining a characteristic of a sample of a biological fluid or a control includes providing an instrument for determining a characteristic of a sample of a biological fluid or a control by combining the biological fluid or control with nontransparent ferromagnetic particles, subjecting the combination to a time varying magnetic field, and detecting the modulation of the transmittance of radiation through the combination.

59. The method of claim 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 or 58 wherein the biological fluid is blood or a blood fraction, and the characteristic of the biological fluid is a coagulation characteristic.