System and method for measuring percent fill of a blood sampling capillary - Patents.com

Abstract

A system and method for measuring the percent fill of a blood sampling capillary includes a chamber for receiving a sample capillary containing a blood sample, an illuminator provided for illuminating the sample capillary, an imaging lens aligned with the chamber and the sample capillary, an imaging sensor aligned with the imaging lens for receiving an image of blood in the sample capillary from the imaging lens and converting the image into image data, a microcontroller circuit electrically connected with the imaging sensor, and at least one of a host computer or a user interface electrically connected with the microcontroller unit, the microcontroller circuit processes the image data to obtain a percent fill result that is sent to the host computer or at least one of a user interface.

Description

Detailed Description of the Invention

[0001] [Background of the invention] 1. Field of the invention The present invention relates generally to a capillary-fill imaging system and method for measuring the percent fill of a blood-sampling capillary.

[0002] 2. Description of the Prior Art Many clinical tests for analytes are performed on biological samples for the purposes of diagnosis, screening, disease staging, drug testing, pregnancy testing, forensic analysis, and other reasons. Although a few qualitative tests have been simplified into simple kits for patient use, the majority of quantitative tests still require sophisticated instrumentation and the expertise of trained technicians in a laboratory environment.

[0003] In recent years, point-of-care devices and systems have been developed that can be operated by nurses and / or caregivers in hospitals, emergency medical centers, clinics, etc., and produce reliable results with minimal training on the device.

[0004] In such point-of-care environments, whole blood samples are typically obtained by puncturing the patient's skin to obtain a blood sample collected by a capillary tube. When using capillary tubes for blood collection purposes, it is essential to obtain a sufficient amount of blood to perform the desired test, but it is desirable to obtain only the amount of blood required. One problem associated with some lancing and / or testing devices is that the requisite amount of blood is not always obtained to obtain an accurate test result. To obtain an adequate blood sample, the user is required to hold the capillary tube against the blood sample until it fills to the proper level. If an inadequate amount is obtained, the test result may be erroneous and the test sample is wasted. A more serious problem, however, is that if an insufficient sample volume is taken, the user may rely on an inaccurate and erroneous test result. Clearly, with the potentially serious nature of medical problems involved, erroneous results must be avoided.

[0005] Several prior art devices have attempted to determine the fill level in liquid systems. U.S. Patent Application Publication No. 2014 / 0105446-A1 (2014, Maxey et al.) discloses a computer-implemented method, software, and system for determining a property of a wellbore fluid. A computing system receives an image of a first sample of wellbore fluid filling a conduit to a threshold capacity of the conduit. The computing system determines a first lifetime of the first sample of wellbore fluid filling the conduit to a threshold capacity of the conduit based on the image of the first sample. The computing system receives an image of a second sample of wellbore fluid filling the conduit to a threshold capacity of the conduit. The computing system determines a second lifetime of the second sample of wellbore fluid filling the conduit to a threshold capacity of the conduit based on the image of the second sample. A property of the wellbore fluid is determined based on a difference between the first lifetime and the second lifetime. The patent publication also mentions using capillary action to fill the conduit tube and to correlate the pixel count of the image based on the fluid level in the tube.

[0006] U.S. Patent No. 6,960,287 (2005, Steven C. Charlton) discloses an underfill detection system for a test sensor. The test sensor includes a capillary flow path for collecting a liquid sample and a conductor disposed outside the capillary flow path. The conductor is in fluid communication with the capillary flow path. When a liquid test sample is collected and moved through the capillary flow path, the sample contacts the conductor to provide a full-fill signal.

[0007] US Patent No. 8,936,713 B2 (Rodgers et al., 2015) discloses a method and system for fill sufficiency. The system discloses a test strip with a first working electrode, a reference electrode, and a second working electrode. The method uses acceptable fill data from a known first current and a known second current to predict an estimated second current about a second time for a given batch of test strips during a test procedure. The estimated second current about the second time interval is compared to a measured actual second current about the second time interval during an actual test to determine whether the measured actual second current is substantially equal to the estimated second current or within an acceptable percentage deviation from the estimated second current to determine whether the physiological fluid sample in the test strip is of sufficient volume.

[0008] [Summary of the Invention] Blood testing instruments can perform an analysis with less than the required blood volume, which can result in errors in the reported value of the analysis. A system for measuring the percent amount of blood that fills the capillary would desirably provide the instrument / analyzer with either a numerical value that can be used to correct the reported value, or a signal to the user that there was an insufficient blood sample, and thus a failure to report a value would result in an inaccurate result being reported to the user.

[0009] As mentioned in the prior art section, one particular document describes a capillary underfill detection system that uses two electrodes to detect the fill level. This requires adding electrodes to the capillary, which increases the cost of the capillary. In another prior art document, the document describes using an imaging device to confirm the flow of the sample in the capillary, but does not describe how to use the imaging device to measure the sample volume.

[0010] It is an object of the present invention to provide a system and method for taking an image of a sample capillary and analyzing the image to determine the percent fill of the capillary.

[0011] The present invention achieves these and other objects by providing a system for measuring the percent fill of a sample capillary. In one embodiment of the invention, the system includes a chamber for receiving a sample capillary containing a blood sample, an illuminator provided for illuminating the sample capillary, an imaging lens aligned with the chamber and the sample capillary, an imaging sensor aligned with the imaging lens for receiving an image of blood in the sample capillary from the imaging lens and converting the image into image data, a microcontroller circuit electrically connected with the imaging sensor, and at least one of a host computer or a user interface electrically connected with the microcontroller unit, the microcontroller circuit processes the image data to obtain a percent fill result, which is sent to at least one of the host computer or the user interface.

[0012] In one embodiment of the invention, the system includes an illuminator that is a white light LED.

[0013] In another embodiment of the invention, the system further comprises an aperture structure aligned with the imaging lens and the imaging sensor, the aperture structure being disposed between the imaging lens and the imaging sensor, the aperture structure confining a cone of light of an image of blood in the sample capillary to reduce image distortions and aberrations caused by the imaging lens.

[0014] In yet another embodiment, the microcontroller circuit controls the illuminator.

[0015] In yet another embodiment, the microcontroller circuit comprises software that extracts pixels of the image of the blood-filled capillary whose pixel values ​​are within a particular range of hues.

[0016] In a further embodiment, the software converts the image data between a first type of color space and a second type of color space.

[0017] In another embodiment, the first type of color space is a color space in YCbCr format.

[0018] In one embodiment, the second type of color space is an HSV format color space.

[0019] In one embodiment, the software is an interpreted high-level general-purpose programming language that includes a first algorithm for converting an image into a YCbCr color space and a second algorithm for converting an image into an HSV color space.

[0020] In one embodiment, the first type of hue space image data and the second type of hue space image data are applied with a mask generation function to generate two masks based on a selected hue range, a mask in YCbCr color space and a mask in HSV color space, and pixels within the selected hue range are set to 1 in the masks and pixels outside the selected hue range are set to 0.

[0021] In one embodiment, a one-dimensional array is generated from the combination of two masks.

[0022] In one embodiment, the system further includes a reference capillary known to be 100% filled with blood or a blood substitute having the required red hue, and image data of the reference capillary defines a calibration value for determining the percent fill of the sample capillary.

[0023] In another embodiment, a method for measuring the percent fill of a sample capillary containing a blood sample is disclosed, which includes: a) placing the sample capillary in the system for imaging analysis; b) taking an image of the sample capillary and converting the image into image data; c) sending image data from the taken image to a microcontroller circuit including software for processing the image data into a first type of hue space data and a second type of hue space data; d) sending the first type of hue space data and the second type of hue space data to corresponding mask generation functions to generate two masks based on a selected hue range; e) combining the two masks to generate a one-dimensional array; and f) determining the percent fill result of the sample capillary by comparing the value generated by analyzing the one-dimensional array with a calibration value.

[0024] In one embodiment, the determining step comprises calculating a difference between a location of the beginning of the blood sample in the image of the sample capillary and a location of the ending of the blood in the image of the sample capillary, and multiplying the difference by a calibration value.

[0025] In one embodiment, a method for generating a calibration value for use in the system of claim 1 is disclosed, comprising generating the calibration value using a reference capillary known to be one hundred percent (100%) filled with blood or a reference capillary known to be one hundred percent (100%) filled with a surrogate material having the required red hue, sending the reference capillary known to be one hundred percent (100%) filled through steps a), b), c), d), e) as previously disclosed, and calculating the calibration value. [Brief description of the drawings]

[0026] [Figure 1]Schematic diagram showing a diagram of the capillary imaging device of the present invention, showing a blood-filled capillary, an illumination source, an imaging sensor, an imaging lens, an optional aperture structure, a microcontroller circuit, and a host computer or analyzer and / or a user interface. [Diagram 2] 1 is a flow chart showing general steps in a process for determining the percent fill of a sample capillary containing a blood sample. [Diagram 3] A color image of a capillary containing a blood sample showing a 100% filled capillary with a start blood line and a finish blood line. [Figure 4] A mask of a color image of a partially filled capillary, separated by hue. [Diagram 5] 13 is a graphical representation of the column-wise sum of the pixels of a mask. [Figure 6] Calculation of capillary filling superimposed on a capillary image of a partially filled capillary, with vertical lines indicating the beginning and end of blood in the capillary as determined by the algorithm. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] [Detailed Description of the Invention] Embodiments of the present invention are illustrated in Figures 1 to 6. Figure 1 is a diagram of a capillary imaging system of the present invention, showing one embodiment. The capillary imaging system 10 comprises a capillary 20 containing a blood sample to be imaged and a percentage of filling to be determined, an illumination source 30, an imaging sensor 40, an imaging lens 50, an optional aperture structure 80, a microcontroller circuit 60, and a host computer or analyzer and / or a user interface 70. The illuminator is a light source, such as a white LED. An image of the capillary 20 is projected by the imaging lens 50 onto the imaging sensor 40. The imaging sensor 40 communicates with the microcontroller circuit 60, which also controls the illumination source 30. Image data from the imaging sensor 40 is processed by the microcontroller circuit, and the results are sent to the host computer or analyzer and / or the user interface 70. The percentage of filling result may be presented to a user of the system, or further processing may be performed by the host computer or analyzer. For example, the host computer may control the entire analyzer with other subsystems and may use the percent fill results from the microcontroller circuit 60 for further calculations and / or corrections of analyte measurements.

[0028] FIG. 2 is a diagram illustrating a process for determining the percent fill of a sample capillary containing a blood sample using the above-described system. The process is outlined as follows: In step 1 (100), an image of the sample capillary is captured. In step 2 (110), the captured image is transformed into two color spaces. In step 3 (120), the image in the new two color spaces is subjected to mask generation functions, one for each of the two color spaces. Then, in step 4 (130), the mask of the first color space and the mask of the second color space are summed / combined pixel by pixel to combine the results of the two masks to obtain a one-dimensional array. In step 5 (140), the one-dimensional array is optionally subjected to erosion and dilation operations to reduce noise. In step 6 (150), the blood start position 80 and blood end position 82 in the image of the sample capillary 20 are determined. In step seven (160), the percent fill of the sample capillary 20 is determined by multiplying the difference between the start of blood position 80 and the end of blood position 82 by the calibration value.

[0029] [Process to calculate filling percentage from capillary image] Referring now to FIG. 3, there is shown a typical image of a capillary containing a blood sample collected from a system such as that shown in FIG. 1. For illustrative purposes only, the capillary in this image is completely filled to the one hundred percent (100%) level. The software or code used to calculate the percent fill from the capillary image is written in the Python programming language. Python is an interpreted, high-level, general-purpose programming language. Python's design philosophy emphasizes code readability through the use of significant indentation. Python's language structure, and its object-oriented approach, are intended to help programmers write clear, logical code for small to large projects.

[0030] Many of the most widely used programming languages ​​(e.g., C++, Java, Python, etc.) are multi-paradigm and typically support more or less object-oriented programming in combination with imperative and procedural programming. Major object-oriented languages ​​include Java, C++, C#, Python, R, PHP, Visual Basic.NET, JavaScript, Ruby, Perl, SIMSCRIPT, Object Pascal, Objective-C, Dart, Swift, Scala, Kotlin, Common Lisp, MATLAB, and Smalltalk. Although the Python language was used, one skilled in the art could rewrite the method written in Python code into any object-oriented language, including the languages ​​listed above.

[0031] The next step in the process is to select the area of ​​the capillary that contains the blood sample. One way to do this is to extract pixels that have values ​​within a particular range of hues. In the present invention, the image is converted into two color spaces: YCbCr and HSV. YCbCr is typically used for digital coding of color information suitable for compression and transmission of moving and still images, for example MPEG and JPEG. HSV (hue, saturation, value), also known as HSB (hue, saturation, brightness), is frequently used by artists because it is considered more natural to think about colors in terms of hue and saturation, rather than in terms of additive or subtractive color components. HSV is a transformation of the RGB color space, whose components and colorimetry are related to the RGB color space from which HSV was derived. Once converted, the image in the new color space is applied with a mask generation function.

[0032] The function call to do this is: 1) Yimg = MT9M114_rgb_to_ycbcr(img) 2) Himg = rgb_to_hsv(img) 3) BWY = createMask(Yimg, 0, 255, 0, 255, 143, 255) 4) BWH = createMaskHSV(Himg, 240, 20, 51, 255, 0, 255)

[0033] The input to the mask generation call indicates the hue range to be selected. Pixels that fall within those values ​​will be set to 1 in the mask, and pixels outside that range will be set to 0. The results of the two masks are combined pixel by pixel using the following logical OR statement: 5) import numpy as np 6) BWYH = np.logical_and(BWY,BWH)

[0034] The resulting array of 1s and 0s is summed column-wise into a one-dimensional array. 7) sBWYH = np.sum(BWYH,0)

[0035] [Algorithm for converting images to YCbCr format (Python language)] To convert the captured image into YCbCr format, the following algorithm is used using Python language.

[0036]

number

[0037] [Algorithm for converting images to HSV format (Python language)] To convert the captured image into HSV format, the following algorithm is used using Python language:

[0038]

number

[0039] [Algorithm for generating a hue mask (Python language)] To generate the hue mask, the following algorithm is used, using the Python language:

[0040]

number

[0041] [Algorithm for finding threshold transitions (Python language)] To find the threshold transition from the column-wise 1D array calculated in step 7, the following algorithm is used (the 1D array contains a variable "f", which is a vector list of numbers, and the term "f[n]" below refers to the nth number of "f").

[0042]

number

[0043] Reference is now made to FIG. 4, which shows a region of an image of a partially filled capillary that has been masked by the logical OR of the two generated masks, with selected portions of the region shown in a reddish color.

[0044] Figure 5 shows a diagram / graph of the column-wise 1D array calculated in step 6, which is the sum of the column values ​​of the logical OR of the two generated masks. The plot shows how many pixels of the selected hue are in each column as a function of the horizontal direction. The array sBWYH is then optionally subjected to erosion and dilation operations to reduce noise. 8) sBWYH = ndimage.grey_erosion(sBWYH,structure=np.ones((50,))) 9) sBWYH = 2 * ndimage.grey_dilation(sBWYH,structure=np.ones((50,)))

[0045] The array sBWYH is then passed to a function findThreshold, which finds the lateral locations of transition points greater than a given threshold of 40. 10) locs = findThreshold(40, sBWYH)

[0046] The beginning of the blood in the capillary is blood beginning position 80 and the end of the blood in the capillary is blood ending position 82 . 11) bloodStart = min(locs) 12) bloodEnd = max(locs)

[0047] The fill percentage value is the difference between the start of blood position 80 and the end of blood position 82 multiplied by a calibration value (calVal). 13) pcntFill = (bloodEnd - bloodStart) x calVal

[0048] [Determination of calibration value (calVal)] The calibration value is previously determined using a reference capillary known to be 100% filled with blood or a substitute such as red dye or red epoxy. Images from this calibration / reference capillary undergo the same processing steps except step 13 is skipped and the calibration value is calculated using step 14 below. 14) calVal = 100.0 / (bloodEnd - bloodStart)

[0049] The calibration / reference capillary can be filled with any material that exhibits the required red hue. The preferred formulation used consists of a mixture of 0.30 grams of UV-curable transparent epoxy NOA81 and 0.06 grams of Congo Red dye powder Sigma C6277-25G (lot number MKCF4499, with 95% dye content). The mixture is pushed into the capillary using a syringe and needle until the capillary is 100% completely filled, and then cured using a UV curing lamp.

[0050] 6 shows the resulting percent fill calculations for a partially filled capillary. The vertical lines in this figure are the locations of where blood begins 80 and ends 82.

[0051] While preferred embodiments of the present invention have been described herein, the above description is by way of example only. Further modifications of the invention disclosed herein will occur to those skilled in the art, and all such modifications are deemed to be within the scope of the invention as defined in the appended claims.

Claims

1. 1. A system for measuring percent fill of a blood-sampling capillary, comprising: a chamber for receiving a sample capillary containing a blood sample; an illuminator provided for illuminating the sample capillary; an imaging lens aligned with the chamber and the sample capillary; an imaging sensor aligned with the imaging lens to receive an image of the blood in the sample capillary from the imaging lens and convert the image into image data; a microcontroller circuit electrically connected to the imaging sensor; at least one of a host computer or a user interface electrically connected to the microcontroller unit; the microcontroller circuit processes the image data to obtain a fill percentage result, the fill percentage result being sent to at least one of the host computer or the user interface. system.

2. 2. The system of claim 1, The system wherein the illuminator is a white light LED.

3. 2. The system of claim 1, further comprising: an aperture structure aligned with the imaging lens and the imaging sensor; the aperture structure is disposed between the imaging lens and the imaging sensor and limits a light cone of the image of the blood in the sample capillary to reduce image distortions and aberrations caused by the imaging lens; system.

4. 2. The system of claim 1, The microcontroller circuit controls the illuminator.

5. 2. The system of claim 1, The microcontroller circuit comprises software that extracts pixels of the image of the sample capillary whose pixel values ​​are within a particular range of hues.

6. 2. The system of claim 1, The software converts the image data between a first type of color space and a second type of color space.

7. 7. The system of claim 6, The system, wherein the first type of color space is a YCbCr type color space.

8. 7. The system of claim 6, The system, wherein the second type of hue space is an HSV type color space.

9. 6. The system of claim 5, The system, wherein the software is an interpreted high-level general-purpose programming language including a first algorithm for converting the image to a YCbCr color space and a second algorithm for converting the image to an HSV color space.

10. 7. The system of claim 6, a mask generation function is applied to the image data in the first type of hue space and the image data in the second type of hue space to generate two masks, a mask in the YCbCr color space and a mask in the HSV color space, based on a selected hue range; Pixels within the selected hue range are set to 1 in the mask and pixels outside the selected hue range are set to 0.

11. 11. The system of claim 10, A one-dimensional array is generated from the combination of the two masks.

12. 2. The system of claim 1, further comprising: a reference capillary known to be 100% filled with blood or a capillary known to be 100% filled with a blood substitute having a required red hue; The image data of the reference capillary defines a calibration value for determining the fill percentage of the sample capillary.

13. 10. A method for measuring the percent fill of a sample capillary containing a blood sample according to claim 1, comprising: a) placing the sample capillary in the system; b) taking an image of the sample capillary and converting the image into image data; c) sending the image data from the captured image to a microcontroller circuit including software for processing the image data into the first type of color space data and a second type of color space data; d) passing the first type of hue space data and the second type of hue space data to corresponding mask generation functions to generate two masks based on a selected hue range; e) combining the two masks to generate a one-dimensional array; and f) determining a percent fill result of the sample capillary containing the blood sample by comparing the value produced by analysis of the one-dimensional array with a calibration value; A method for providing the above.

14. 14. The method of claim 13, The determining step includes: calculating a difference between a position of the start of the blood sample in the image of the sample capillary and a position of the end of the blood in the image of the sample capillary; multiplying the difference by the calibration value; A method for providing the above.

15. 14. The method of claim 13 further comprising: generating a calibration value using a reference capillary known to be one hundred percent (100%) filled with blood or a capillary known to be one hundred percent (100%) filled with a surrogate material having the required red hue; passing said reference capillary, known to be one hundred percent (100%) filled, through steps a), b), c), d) and e); calculating said calibration value; A method for providing the above.

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