Analyte detection devices and methods with hematocrit/volume correction and feedback control

Abstract

Disclosed are devices, arrangements and methods for quantifying the concentration of an analyte present in bodily fluid, including: an assay pad having at least one chemical reagent capable of producing a detectable signal in the form of a reaction spot upon reaction with the analyte; a light source; a detector array; a processor; and a memory in communication with the processor, the memory comprising: (a) at least one value indicative of one or more of: (i) the level of hematocrit contained in the sample; (ii) the volume of the sample applied to the assay pad; or (iii) imperfections present in the reaction spot; and (b) at least one algorithm for calculating the concentration of the analyte contained in the sample.

Claims

1. A method of collecting a body fluid sample using an analyte meter comprising an assay pad and a detector including a detector array, the method comprising: applying a catalyst to a sampling site of a user to facilitate acquisition of the body fluid sample; transporting the body fluid sample to the assay pad; imaging the assay pad using the detector; determining, via a processor configured to perform the determining, whether the assay pad has received a sufficient sample volume from the sampling site, the sufficient sample volume being based on data from individual pixels of the detector array; and altering or maintaining, via the processor, the application of the catalyst to the sampling site based on the determining step, wherein the processor is further configured to control the altering or maintaining.

2. The method of claim 1, wherein the catalyst is vacuum, heat, pressure, or vibration.

3. The method of claim 1, wherein altering or maintaining the application of the catalyst comprises stopping, via the processor, the application of the catalyst.

4. The method of claim 1, wherein altering or maintaining the application of the catalyst comprises increasing or decreasing, via the processor, a magnitude of the catalyst.

5. The method of claim 1, wherein the detector array comprises a linear array of detector elements, and the detector elements comprise CMOS, CCD, photodiode, infrared, fluorescent, ultraviolet or electrochemical elements.

6. The method of claim 1, wherein the detector array is larger than the assay pad.

7. The method of claim 1, wherein imaging the assay pad using the detector comprises imaging a reaction spot formed on the assay pad by a reaction between a reagent on the assay pad and an analyte in the body fluid sample.

8. The method of claim 7, wherein imaging the reaction spot comprises imaging a color change at the reaction spot.

9. The method of claim 7 further comprising determining, via the processor, a concentration of the analyte from the reaction spot.

10. The method of claim 9, wherein the analyte comprises glucose and the body fluid sample comprises blood.

11. The method of claim 1, wherein determining whether the assay pad has received a sufficient sample volume comprises estimating, via the processor, a volume of a sample received on the assay pad.

12. The method of claim 1, wherein determining whether the assay pad has received a sufficient sample volume comprises predicting, via the processor, a volume of a sample anticipated to be received on the assay pad, wherein the processor is further configured to perform the predicting.

13. The method of claim 1, wherein determining whether the assay pad has received a sufficient sample volume comprises determining, via the processor, that the assay pad has received a sufficient sample volume, the processor being further configured to perform the determining that the assay pad has received the sufficient sample volume, and altering or maintaining the application of the catalyst to the sampling site comprises stopping, via the processor, the application of the catalyst.

14. The method of claim 1, wherein determining whether the assay pad has received a sufficient sample volume comprises determining, via the processor, that the assay pad has received an insufficient sample volume, the processor being further configured to perform the determining that the assay pad has received the insufficient sample volume, and altering or maintaining the application of the catalyst to the sampling site comprises maintaining, via the processor, the application of the catalyst.

15. The method of claim 14 further comprising imaging the assay pad using the detector after maintaining the application of the catalyst and determining, via the processor, whether the assay pad has received a sufficient sample volume for a second time.

16. The method of claim 14, wherein the catalyst is vacuum.

17. The method of claim 1, wherein the analyte meter comprises a skin-penetration member in fluid communication with the assay pad, and the method further comprises piercing skin of the user with the skin-penetration member.

18. The method of claim 1 further comprising quantifying, via the processor, an analyte concentration in the body fluid sample via a photometric method, wherein the processor is further configured to perform the quantifying.

19. The method of claim 1, wherein the analyte meter comprises a catalyst device.

20. The method of claim 19, wherein the catalyst device comprises a vacuum pump, a motor for producing vibration, or a heating element.

21. The method of claim 1, wherein transporting the body fluid sample to the assay pad comprises transporting the body fluid sample using a hollow needle.

22. The method of claim 1, wherein the processor is further configured to determines whether the assay pad has received a sufficient sample volume based on a number of pixels in the detector array that have detected a predetermined threshold color change.

23. The method of claim 13, wherein the processor is further configured to determine that the assay pad has received a sufficient sample volume based on a number of pixels in the detector array that have detected a predetermined threshold color change.

24. The method of claim 15, wherein the processor is further configured to determine that the assay pad has received an insufficient sample volume and to determine whether the assay pad has received a sufficient sample volume for a second time based on a number of pixels in the detector array that have detected a predetermined threshold color change.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The preferred embodiments are illustrated in the drawings in which like reference numerals refer to the like elements and in which:

(2) FIG. 1 is a flow diagram of a mode of operation according to certain aspects of the present invention.

(3) FIG. 2 is a schematic illustration of an arrangement formed according to the principles of the present invention.

(4) FIG. 3 is a schematic diagram of a portion of the arrangement of FIG. 2.

(5) FIG. 4 is a perspective view of a device formed according to an embodiment of the present invention.

(6) FIG. 5 is a partial cutaway view of FIG. 4.

DETAILED DESCRIPTION OF THE INVENTION

(7) Exemplary arrangements and methods for the detection and measurement of the presence and/or concentration of a target analyte, such as glucose, bilirubin, alcohol, controlled substances, toxins, hormones, proteins, etc., will now be described.

(8) In broader aspects, the current invention provides the ability to correct for broad variations in sample hematocrit levels in the measurement of an analyte, such as glucose, during the course of the test. The invention takes advantage of an imaging array of detectors to perform this correction and does not require any additional hardware. In other words, no other distinct sensors or detectors, other than the imaging array, are required to calculate the correction. The very sensor that is used to quantify the analyte within the sample may also correct for hematocrit. Strategic algorithms that process the data from the imaging array provide real-time or near real-time information about the sample hematocrit level. Thus, more accurate results, regardless of the hematocrit level of the user, may be obtained via correction based on the hematocrit level of the sample.

(9) The current invention may also use appropriate algorithms to permit real-time sensing of the amount of sample volume delivered to an assay pad. With this information, appropriate calibration parameters may be selected corresponding to the actual delivered volume. To correct for sample volume, algorithms similar to those used for hematocrit correction may be used, where volume is substituted for hematocrit and a unique formulation and corresponding constants are determined.

(10) The present invention offers the flexibility to improve the accuracy of measured glucose for a broad range of sample volumes that are typically delivered to the assay pad of the meter system. In addition, sampling catalysts such as vacuum, heat, pressure, etc. may be implemented or provided automatically by the device to help ensure sufficient sample volume is collected and analyzed. The invention provides information to the meter system to know when and how much of the catalyst is sufficient. Since the invention can measure or estimate the volume of the sample delivered to the assay pad, it can also provide feedback to start, maintain or terminate the catalysts, as well as increase or decrease the magnitude of the catalyst, based on this measured volume. This offers the advantage of adapting the device function to the user's real-time skin physiology, minimizing the risks associated with the catalysts (bruising, scarring, excessive bleeding), reducing the energy consumed by the system, and reducing the chance of a wasted test operation (and the associated user's time, battery supply, and cost of test strip) by ensuring a minimum sample volume is obtained, as well as minimizing the overall time to get a result from the system.

(11) According to additional broad aspects, the present invention can process data received from the detector array to compensate for irregularities or imperfections present in a reaction spot in order to improve accuracy of the analyte concentration method. The present invention includes devices, arrangements and methods that include any of the above referenced aspects individually, as well as combinations of some or all of these aspects.

(12) The current invention may employ a linear CMOS imaging detector array. Contrary to other approaches that describe the use of 2-D CCD imaging detector arrays, the linear CMOS array detects light across a single row of optical detectors (pixels) whose output is proportional to the amount of light incident to the pixel. Linear detector arrays offer an advantage over 2-D imaging systems in simplicity and efficiency in processing the image information as long as the expected location of reagent chemistry reaction or reagent spot is known and the associated light, which may be supplied by an LED, is reflected from this area and is imaged appropriately by the CMOS array.

(13) The CMOS detector array may have an overall size that is comparable to the size of the assay pad and the expected range of spot sizes that develop on the pad. According to one alternative, the detector can be larger than the size of the pad. This construction can allow wider tolerances in the relative position of the assay pad and the detector, and provide for additional in-process error detection and recovery (e.g., detecting or correcting for assay pad motion).

(14) In addition to light sources such as LED's, various optical components such as lenses, diffusers, light pipes, etc. may be integrated into the system to optimize the image size and resolution. Such a system may utilize a commercially available linear CMOS detector array such as part #TSL1401R or TSL1401CS; from TAOS, Plano, Tex. This detector has 128 pixels across an array of ˜19 mm in length. Light reflected off of white surfaces, such as an unreacted reagent pad, and received by the CMOS detector results in a signal from each pixel that is conditioned to produce a near maximum response up to 5 volts. Darker surfaces, such as from a color change associated with a reagent spot, will produce lower voltage response for each pixel depending on the reagent chemistry, light source, optical path, and ultimately, the concentration of the analyte (e.g., glucose).

(15) A number of different arrangements comprising a quantification member, such as an assay pad, a sensor or detector, and one or more additional components are contemplated by the present inventions. Additional exemplary arrangements are described in U.S. application Ser. No. 10/394,230, entitled ANALYTE CONCENTRATION DETECTION DEVICES AND METHODS, the entire content of which is incorporated by reference herein.

(16) When coupled with an assay pad containing a photometric reagent, the sensor detects the change in color of the pad, and the output is processed as a change in voltage relative to that of the original reagent color. Typically, about 10-50% of the pixels across the array are sufficient to resolve a spot of color change, but this can depend on a variety of factors, including CMOS sensor design, sample volume size, reagent dynamics, and the optical path between the pad and sensor.

(17) Since the arrangements and techniques of the present invention can perform the assay without all of the pixels in the sensor array being in optical registry with the reagent spot, it is contemplated by the present invention to utilize these free pixels in one or more possible ways. For example, a second assay may be performed at a different area of the same assay pad, or on separate assay pad, at a location corresponding to the aforementioned unused pixels. The unused pixels may be used for calibration or as a control. For instance, a control solution having a known concentration of analyte may be introduced in the area of the assay pad, or onto a separate pad, in the area of the unused pixels. The control solution reacts with the reagent and the signal produced by pixels can be calibrated in accordance with the known analyte concentration. According to another alternative, a means for calibrating the reagent for lot information may be provided in the area of the unused pixels, thereby eliminating the need for the user to set reagent lot calibration codes. A similar arrangement and technique would be to utilize a standard color in registry with the unused pixels that produces a known reflectance signal. Upon reading this known signal, the arrangement, via a microprocessor and associated software and electronic components, can verify whether or not the device is functioning properly.

(18) According to certain embodiments, sensor data can be acquired with an analog-to-digital capture device, such as a PC board, and processed as a linear dimension data array whose size corresponds to the number of pixels in the imaging array, such as 128 or 256 pixels. This data array will change over time as the reaction between the analyte (glucose) and the reagent enzymes develops, reaches saturation and begins to dry out.

(19) According to one embodiment, the current invention incorporates an algorithm for processing the information in the data array over time to detect and correct for the hematocrit in the blood sample. The rate of color change over time across the detector array, and thus rate of change in signal of the data array, is dependent upon the relative amount of plasma in the sample. A relatively high plasma content in a given sample size will cause the sample to react with the reagent chemistry faster and develop a change in color more quickly than a relatively smaller plasma content. Since hematocrit level is inversely proportional to plasma content, the rate of color change can be scaled inversely to hematocrit level.

(20) The relation between rate of color change and hematocrit level will depend upon a variety of variables, including the volume of the sample delivered to the assay pad as well as the inherent reagent chemistry, optical path, light source and detector array. Consequently, a unique correlation calibration between color change rate as detected by the CMOS imager and blood hematocrit level can be empirically determined and programmed into a memory device as a lookup table, or calculation.

(21) Exemplary, non-limiting algorithm formulations to accomplish the above include: 1. Hct α δA(x,t)/δt; where Hct=hematocrit, α implies proportional to, δ/δt=is the partial derivative with respect to time (a measure of rate of change), and A(x,t) is a measure of the array signal strength in the sensor at position x at time t. Proportionality may be linear and of the form Hct=m(δA(x,t)/δt)+C; where m and C are constants determined empirically. Hematocrit proportionality correction may also be better represented by polynomial, exponential, power or other functions. 2. Hematocrit α δA(x,t)/δx; where Hct and α are as defined above, and δ/δx=is the partial derivative with respect to position x. Again, proportionality may be linear and of the form Hct=m(δA(x,t)/δx)+C; where m and C are constants determined empirically. Proportionality may also be non-linear and represented by logarithmic, polynomial, exponential or other equations. 3. Hematocrit α δA(x,t)/δx δt; where Hct and α are as defined above, and δ/δx δt=is the partial derivative with respect to position x and time t. 4. Hematocrit α δ.sup.2A(x,t)/δ.sup.2×δ.sup.2t; where Hct and α are as defined above, and δ.sup.2/δ.sup.2×δ.sup.2t=is the second order partial derivative with respect to position x and time t.

(22) Pixel position x ranges from the lower to upper limits and in the case of a 256 pixel array, would range from 1 to 256. For a variety of reasons, the algorithm may be limited to the evaluation of specific positions or ranges within the array, such as between x=x_lower and x=x_upper, where x_lower may be 40 and x_upper may be 80.

(23) Time t as referred to in these algorithms can refer to the time elapsed between known events within the analyte quantification process. For example, t=0 may be defined at the point in which blood is first presented to the reagent membrane, or when the imaging array first detects a predetermined threshold change corresponding to the arrival of the analyte to the reagent membrane.

(24) Array signal strength A(x,t) corresponds to a measure of the color of the reagent membrane. Typically, this signal is initially processed as a voltage or a current. Those skilled in the art of photometric reagent signal process will appreciate that subsequent transformation of this data into a measure of normalized reflectance R and/or to absorption via the well-known calculation of K/S may be represented by A(x,t). For example:

(25) K/S (x,t)=(1−R).sup.2/2R; where R=A(x,t).sub.Reacted/A (x,t).sub.Unreacted, where A(x,t).sub.Unreacted refers to the array signal corresponding to the reagent membrane prior to any reaction with the analyte, and A(x,t).sub.Reacted the array signal corresponding to the membrane as it reacts with the analyte at array position x at time t.

(26) Those skilled in the art will appreciate that combinations of these and/or other similar algorithms would mathematically capture the relation between hematocrit and the rate of change of spot development in the membrane. Furthermore, the skilled reader would appreciate that the proportionality constants (m and C) are dependent upon the conditions of the reagent membrane (material, chemistry, lighting), the hardware and software specifications, and the nature and method in which the analyte is delivered to the membrane.

(27) Thus, the appropriate calibration factor relating reflected light to glucose concentration would then be chosen based on the hematocrit level. When the consumer uses the device, the meter detects color change and applies the correct calibration factor for the user's hematocrit level to the calculation of glucose content made by an algorithm also contained in the same, or a different memory device.

(28) As an example of the above, if the glucose calibration curve is of the form:

(29) R=m×[Glucose Concentration]+b; where R=the as-measured reflected light signal, and m and b are empirically determined constants.

(30) A corrected signal 12, could be derived from a look-up table of correction factors, F.sub.h, as a function of hematocrit level:
R.sub.c=F.sub.h×R

(31) This corrected signal would then be substituted into the above equation to calculate the hematocrit-adjusted glucose concentration.

(32) Processing the data generated by the change in color caused by the reaction between the analyte and reagent chemistry in conjunction with the speed and capacity of today's microprocessors would not add to the required time to process the sample, yet would substantially increase the accuracy and reduce the variability for analyte concentration measurements associated with different whole blood hematocrit levels.

(33) Various alternatives and modifications to the above-described embodiment related to detector data analysis to determine hematocrit levels are possible. For example, such alternatives and modifications include one or more of: evaluating the rate of pixel signal changes with respect to time; evaluating the rate of pixel change with respect to time and with respect to associated pixels that also are changing (i.e., spatial and temporal rate of change); evaluating the rate of pixel change with respect to time for an individual pixel; evaluating the rate of pixel change with respect to time for multiple pixels; evaluating the rate of pixel change with respect to time for the pixel that detects the largest change in color when enzymatic reaction and color change is complete; evaluating the rate of pixel change with respect to time for the pixel that detects the largest change in color during the ongoing enzymatic reaction; evaluating the rate of pixel change with respect to time for the pixel that detects the largest change in color after a lapse of a predetermined amount of time before any enzymatic reaction has actually occurred; and evaluating the resolved volume of the sample (as described earlier) at a specific time for which a fixed, prescribed amount of blood has been delivered to the reagent pad (since measured sample size is proportional to plasma volume, which is inversely proportional to hematocrit).

(34) Using the aforementioned detector array, the invention also contemplates novel arrangements, devices and methods for quantifying, in real-time, the amount of sample delivered to an analyte quantification member, such as an assay pad. This method takes advantage of the discrete data provided by individual detector elements or pixels. As a reaction spot begins to develop in the assay pad, the system described earlier can resolve a particular dimension associated with the size of the spot, such as width. This invention does not require that the spot be of a particular shape, such as round, square, or rectangular, as long as the detector array is oriented to resolve at least one dimension of the spot that is proportional to sample volume. Assuming the assay pad and the method by which the blood is delivered to the pad has been optimized to reduce the variability in spot development, the spot size will be proportional to the volume of blood sample.

(35) The imaging system can resolve the spot size by identifying how many pixels or detector elements have detected a color change. Although the color change associated with the chemical reaction between analyte and enzyme may not be completed or reached equilibrium, the quantification of the number of pixels that have detected a predetermined threshold change in color will be proportional to the spot size. Thus, a real-time assessment of the spot size and thus volume can be computed.

(36) Accordingly, the effect on glucose concentration calculations associated with various sample volumes may be empirically determined, and a lookup table, equation, or calculation incorporated in a memory device which may then be used to select an appropriate predetermined calibration factor to provide a more accurate reading of the analyte concentration for a particular sample volume. Thus, an appropriate calibration factor based on the actual sample volume may be applied to an algorithm used to calculate glucose concentration.

(37) As an example of the above, if the glucose calibration curve is of the form:

(38) R=m×[Glucose Concentration]+b; where R=the as-measured reflected light signal, and m and b are empirically determined constants. A corrected signal R.sub.c, could be derived from a look-up table of correction factors, F.sub.v, as a function of sample volume:
R.sub.c=F.sub.v×R

(39) This corrected signal would then be substituted into the above equation to calculate the volume-adjusted glucose concentration.

(40) Various alternatives and modifications to the above-described embodiment related to detector array data analysis to determine sample size are possible, for example, such alternatives and modifications include one or more of: computing the number of pixels that have detected a change in color above a prescribed constant threshold at a particular point in time during the enzymatic reaction; computing the number of pixels that have detected a change in color above a prescribed constant threshold at multiple points in time during the enzymatic reaction; computing the number of pixels that have detected a change in color above a prescribed constant threshold at a time in which the enzymatic reaction is complete; computing the number of pixels that have detected a change in color above a variable threshold across the array; using above strategies to correlate output to actual sample volume at reagent pad; and using above strategies to predict sample volume to be delivered to assay pad after a predetermined amount of time.

(41) Using the aforementioned detector array to detect the volume of the sample, the volume information can be used as feedback information, and utilized in devices such as an integrated meter. The definition of an integrated device or meter in this context includes one which includes the functions of acquiring a sample of body fluid or blood from the skin, transporting the body fluid or blood from the skin to a quantification area or assay pad, and quantifying the analyte (e.g. —glucose) in the sample via a photometric method.

(42) In this embodiment, a catalyst such as vacuum, heat, pressure, vibration or similar action is preferably applied to the sampling site to facilitate the acquisition of sufficient sample volume of blood. Catalysts such as these can be effective in expressing sufficiently large volumes of blood even from alternative body sites that are less perfused than the fingertips. To ensure that the catalyst is applied with sufficient magnitude and duration, this invention provides a construction and method to control the catalyst such that it operates for exactly as long as necessary. By quantifying the sample volume delivered to the reagent pad in real-time, the detector array and associated on-board data processing within the integrated device can provide a feedback signal via a digital microprocessor controller or similar device which indicates either to increase, decrease, or keep constant the magnitude of the catalyst, as well as to either continue or stop the application of the catalyst. Those experienced in the art of controlling such catalyst mechanisms will appreciate that the control signal may be either binary or analog and use this information accordingly to control a pump (for vacuum/pressure), a motor (for vibration), a heating element (for increasing skin temperature) or combinations thereof.

(43) One such exemplary mode of operation is illustrated in FIG. 1. As illustrated therein, a suitable catalyst, such as a vacuum created by a suitable mechanism or pump is initiated. Shortly thereafter the signals from the detector array are analyzed and the sample volume estimated. This volume is compared with a target sample volume. If the volume is sufficient, the catalyst is turned off. If the volume is insufficient, the reading and calculating processes are repeated until such time as the target sample volume is reached. Once the target sample volume is reached, the analyte concentration determination may continue.

(44) Various alternatives and modifications to the above-described embodiment related to detector array data analysis to provide feedback are possible. For example, such alternatives and modifications may include one or more of: providing a feedback signal corresponding to actual sample volume received at the assay pad; providing a feedback signal corresponding to predicted volume anticipated to be delivered to assay pad; providing an analog feedback signal that is proportional to the volume received at the assay pad; providing a digital feedback signal that indicates either sufficient or insufficient quantity of sample volume received; providing feedback signal based on imaging of an alternative location within the meter that is not necessarily the reagent pad, but can also be imaged by the detector array to detect whether a specific threshold of blood will be delivered to the reagent pad; and providing feedback signal based on imaging of an alternative location outside of the meter (such as on the skin) that can also be imaged by the detector array to detect whether a specific threshold of blood will be delivered to the assay pad.

(45) The discrete nature of the detection elements or pixels also allows for detection of flaws and to distinguish them from regions of the reaction spot that are developing an appropriate or more ideal photometric reaction, even if they are randomly distributed.

(46) For example, a detector array is arranged to scan the reaction spot, optionally coupled with appropriate optical magnification. An ideal spot will produce little or no variation in signal response across the array. In the case of a non-ideal spot, the response of the pixels will vary spatially and temporally. A quantification algorithm which has one or more of the following features could correct and/or ignore the reaction spot flaw(s) and have the potential to provide a more accurate measurement of the analyte concentration: identification and inclusion of data only from pixels which correspond to the appropriate and expected color (e.g., screen for data corresponding to various shades of blue only); identification and exclusion of data from pixels which do not correspond to the appropriate and expected color (e.g., screen out data corresponding to shades of red); inclusion/exclusion of pixel information which does not change at a rate with respect to time expected for the appropriate color (e.g., rate of change of blue is not the same as that of non-blue pixels); and inclusion/exclusion of pixel information which does not change at a rate with respect to time after a specific elapsed time or during a specific time window expected for the appropriate color (e.g., blue pixels change from time t1 to t2 by x %, whereas non-blue pixels do not change by x % between time t1 through t2).

(47) Combinations of the above strategies or similar ones may allow the algorithm to successfully correct for non-ideal spots. It may even be the case that a relatively small percentage of the spot area actually is ideal, yet if the detector array can image this area, even 1 pixel could be sufficient to provide an accurate reading of the analyte.

(48) FIGS. 2-3 are schematic illustrations of at least some of the aspects of arrangements, devices and methods of the present invention. As illustrated therein, an arrangement 10, such as an integrated device or meter may include a detector array 20, which can be provided in the form of a linear array of individual detection elements 30. Each detection element 30 is capable of producing a signal. The detection elements 30 may comprise one or more CMOS-based detection elements or pixels. The linear array 20 is generally in optical registry with an assay pad 40. The relative vertical position of the assay pad and detector array 20 may, of course, differ from the illustrated embodiment. In addition, the assay pad 40 and the detector array 20 may have a geometry that differs from that of the illustrated embodiment. The detector array 20 may be larger than the assay pad 40.

(49) The assay pad 40 preferably contains at least one reagent. A mechanism may be provided to transport a sample of body fluid, such as blood, to the assay pad 40. According to the illustrated embodiment, a hollow member 60, such as a needle, having one end in fluid communication with the assay pad may provide a mechanism for transport. As a sample of body fluid is applied to the assay pad 40, a reaction between the reagent and the analyte of interest (e.g., glucose) results in a color change on a surface of the assay pad 40 forming a reaction spot 50 in optical registry with the array of detector elements 30. The detector array 20 corresponds in location to the spot 50 produces a signal in response to the color change that is indicative of the presence of the analyte of interest. The signal can be used to estimate the volume of the sample applied to the reagent pad, monitor the kinetics of the reaction between the reagent and the analyte, and ascertain irregularities in the reaction spot 50, as described above. This information can then be used to correct the output (e.g., concentration of analyte present in the sample) of the device to account for the hematocrit level, volume of sample presented to the assay pad 40, and/or irregularities in the reaction spot 50. The above-described arrangement 10 of features may all be contained or integrated within a single device or meter. Alternatively, one or a combination of any of the above-described features may be incorporated into such a device.

(50) The detector array 20 forms part of an arrangement 70 present in the device 10 for carrying out the various operations described herein. As best illustrated in FIG. 3, the detector 20 may contain a plurality of detector elements in signal communication with a device 72 having timing and control logic. The timing and control logic may include internal as well external control signals. These signals typically include clock and frame start signals. External timing and control signals may be generated by a microprocessor/microcontroller or other external circuitry. The detector array 20 may have analog signal output. Alternatively, the detector 20 may have a digital data interface.

(51) As illustrated, the detector may comprise an internal signal amplifier 74. Alternatively, the signal amplifier 74 may be external, as indicated by the amplifier 74 shown in broken line. According to another alternative, the amplifier 74 may be entirely omitted. According to yet another alternative, both an internal and external amplifiers 74 may be provided.

(52) The signal from the detector 20 is outputted to an analog/digital converter 76 (where no digital data interface is provided by the detector). The converter 76 is connected to a bus 78, along with a memory 80 and an input/output device 82. The memory 80 may comprise one or more of RAM, ROM or EEPROM, as well as other conventional memory devices. Whatever its form, the memory 80 preferably contains at least one value indicative of hematocrit level, sample volume or reagent spot imperfections. In this regard the memory may contain one or more of the algorithms and look-up tables described herein.

(53) The converter 76, the bus 78, the memory 80 and input/output device 82 may be components of a microprocessor/microcontroller 84. According to an alternative embodiment, the converter 76, memory 80 and input/output device 82 are external to the microprocessor/microcontroller 84.

(54) The input/output device 82 is in signal communication with various output devices 86, 88, 90, 92, and can provide control signals thereto. These output devices may include a device providing a catalyst to facilitate sample acquisition, as described herein. For example, these devices may include one or more of a vacuum pump, an actuation trigger device, a light source, a heat source, a vibration motor, or combinations of any of the foregoing. Regardless of the form of these devices, they are configured and arranged such that they are in signal communication with input/output device 82 so as to be responsive to the control signals. These control signals may be based on sample volume calculations made with the assistance of the detector array, as described herein.

(55) An integrated device formed according to the principles of the present invention may have a number of suitable configurations. According to certain embodiments the device is configured to perform testing by acquiring a sample of blood from the user, transfer the sample to an analysis site, and determine the concentration of a target analyte contained in the sample. These operations are all performed with little or no user input. For example, these operations may commence automatically according to a specified or predetermined schedule. Alternatively, these operations may commence at the command of the user via, for example, pressing a start button on the device.

(56) The device may include disposable and reusable portions. The disposable portion may include at least one skin piercing element/transport member and analysis site (which may include an assay pad). The disposable portion may provide the capability to perform a single test. After testing is complete, the disposable portion is discarded and replaced with a new disposable portion before performing another test. Alternatively, the disposable portion includes a plurality of skin piercing elements/transport members and analysis sites. Such disposable units permit a plurality of tests to be performed before it is necessary to discard and replace the disposable unit. The device may be either wearable or handheld, or both.

(57) A non-limiting exemplary integrated device 100 is illustrated in FIGS. 4-5. As illustrated therein the device 100 generally comprises a functional portion 102, and an optional attachment means or band 104. Thus according to the present invention, the integrated device 100 may be wearable. In addition, or alternatively, the integrated device may be operable as a hand-held device. For example, according to the illustrated embodiment, the band 104 can be separated and/or otherwise removed from the user, and the device 100 stored in a suitable case or in the user's pocket. The band can then be grasped and used to hold the device against the skin to perform a testing operation.

(58) The device 100 preferably includes at least one arrangement for performing a measurement of the concentration of an analyte contained in a sample of blood. According to the illustrated embodiment, the device 100 comprises at least one skin-piercing element, at least one actuation member, such as a torsional spring element as described in further detail herein, and at least one analysis site 110, which may contain an assay pad. The at least one arrangement may form part of a disposable portion or unit. According to one embodiment, the disposable unit allows for at least one measurement of the concentration of an analyte contained in a sample of blood prior to being discarded and replaced. According to a further embodiment, the disposable unit allows for a plurality of measurements of the concentration of an analyte contained in a sample of blood prior to being discarded and replaced.

(59) According to certain alternative embodiments, the device may additionally contain one or more of the features disclosed in U.S. Pat. No. 6,540,975, U.S. Patent Application Publications 2003/0153900, 2004/0191119, and published PCT Applications WO 04/085995 and WO 04/0191693, the entire contents of which are incorporated herein by reference.

(60) While this invention is satisfied by embodiments in many different forms, as described in detail in connection with preferred embodiments of the invention, it is understood that the present disclosure is to be considered as exemplary of the principles of the invention and is not intended to limit the invention to the specific embodiments illustrated and described herein. Numerous variations may be made by persons skilled in the art without departure from the spirit of the invention. The abstract and the title are not to be construed as limiting the scope of the present invention, as their purpose is to enable the appropriate authorities, as well as the general public, to quickly determine the general nature of the invention. Unless the term “means” is expressly used, none of the features or elements recited herein should be construed as means-plus-function limitations pursuant to 35 U.S.C. § 112, ¶6.