Point of care diagnostic systems

• US 6,936,476 B1
• Filed: 11/20/2000
• Issued: 08/30/2005
• Est. Priority Date: 02/03/1998
• Status: Expired due to Term

• Current Assignee: Cytyc Corporation (Hologic Incorporated)
• Original Assignee: Cytyc Prenatal Products Corp. (Hologic Incorporated)
• Inventors: Senyei, Andrew E., Martinez, Ricardo, Anderson, Emory V., Marzolf, Gail, Nemec, Edward, Pong, Ronald, Jones, Lynn, Lapointe, Jerome, DeSieno, Duane, Hussa, Robert O.
• Primary Examiner(s): Le, Long V.
• Assistant Examiner(s): Davis, Deborah A
• Application Number:
  US09/717,355
• Time in Patent Office: 1,744 Days
• Field of Search: 436/65, 436/518, 436/811, 436/510, 436/536, 422/82.09, 422/56, 422/82.11, 356/434, 435/7.21, 435/7.1
• US Class Current: 436/518
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 2333/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: G01N 2800/368 Pregnancy complicated by disease or abnormalities of pregnancy, e.g. preeclampsia, preterm labour
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue
• CPC Class Codes: G01N 33/689 related to pregnancy or the gonads
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 10/60 for patient-specific data, e.g. for electronic patient records
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 30/40 for processing medical images, e.g. editing
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 436/811 Test for named disease, body condition or organ function
• CPC Class Codes: Y10S 436/814 Pregnancy

Abstract

Systems and methods for medical diagnosis or risk assessment for a patient are provided. These systems and methods are designed to be employed at the point of care, such as in emergency rooms and operating rooms, or in any situation in which a rapid and accurate result is desired. The systems and methods process patient data, particularly data from point of care diagnostic tests or assays, including immunoassays, electrocardiograms, X-rays and other such tests, and provide an indication of a medical condition or risk or absence thereof. The systems include an instrument for reading or evaluating the test data and software for converting the data into diagnostic or risk assessment information.

Claims

1. A method for determining a risk or identifying a condition associated with the presence of fetal fibronectin (fFN) in a cervicovaginal sample, comprising:

obtaining a cervicovaginal sample and reacting it with an antibody on a lateral flow test device to produce an image on the test device indicative of the presence of fFN in the sample;

moving a reader head in a reflectance reader to a position over the test device;

measuring a first amount of light reflected from a surface that comprises the image;

uniformly illuminating the surface with light of a first wavelength, and measuring a second amount of light reflected from the surface;

uniformly illuminating the surface with light of a second wavelength, and measuring a third amount of light reflected from the surface; and

repeating each of the measuring and illuminating steps at additional positions on the surface until the surface of the test device that comprises the image is scanned, thereby providing data to determine the intensity and shape of the image to indicate the presence or amount of fFN in the sample.

2. The method of claim 1, further comprising correlating the amount of fFN with the risk of developing a pregnancy related condition or with the presence of the pregnancy related condition.

3. The method of claim 1, further comprising correlating the amount of fFN in the sample to assess fertility status.

4. The method of claim 2, wherein the pregnancy related condition is selected from the group consisting of ectopic pregnancy, infertility, preterm labor, pre-eclampsia, imminent delivery, term induction and fetal membrane rupture.

5. The method of claim 1 wherein, prior to reacting the sample with the antibody on the lateral flow test device, the sample is reacted with an antibody labeled with a detectable label.

6. The method of claim 1, wherein the reader head comprises:

a reader head body;

a light emitting diode;

a first fiberoptic bundle optically coupled to the light emitting diode;

a photodetector;

a second fiberoptic bundle optically coupled to the photodetector;

an aperture in the reader head body; and

a plurality of fiberoptic conductor ends arranged in a sigmoidal distribution in the aperture, wherein;

a first portion of the fiberoptic conductor ends comprises fiberoptic conductors of the first fiberoptic bundle; and

a second portion of the fiberoptic conductor ends comprises fiberoptic conductors of the second fiberoptic bundle.

7. The method of the claim 1, wherein the reader further comprises,

a control unit including a processor modified with a software subsystem, wherein the software subsystem is for analyzing data produced in the steps of measuring the first, second and third amounts of light reflected from the surface.

8. The method of claim 1, wherein the reflectance reader comprises:

the reader head comprising;

a reader head body;

a light emitting diode;

a first fiberoptic bundle optically coupled to the light emitting diode, and adapted to transmit light from the light emitting diode;

a photodetector adapted for generating a reflection signal in response to reflected light;

a second fiberoptic bundle optically coupled to the photodetector, and adapted to transmit an amount of reflected light to the photodetector;

an aperture in the reader head body; and

a plurality of fiberoptic conductor ends arranged in a sigmoidal distribution in the aperture, wherein;

a first portion of the fiberoptic conductor ends comprises fiberoptic conductors of the first fiberoptic bundle; and

a second portion of the fiberoptic conductor ends comprises fiberoptic conductors of the second fiberoptic bundle, the plurality of fiberoptic conductor ends being further arranged in a substantially co-planar relationship; and

a reader housing comprising;

a housing body; and

a cassette slot adapted to receive a test device.

9. The method of the claim 8, wherein the reader further comprises,

a control unit including a processor modified with a software subsystem, wherein the software subsystem is for analyzing data produced in the steps of measuring the first, second and third amounts of light reflected from the surface.

12. The method of claim 1, wherein the step of measuring a first amount of light is carried out while no light is produced by a light source in the reader head.

13. The method of claim 1, wherein the first wavelength is blue.

14. The method of claim 1, wherein the second wavelength is amber.

15. The method of claim 1, wherein the measuring the first amount of light is used to determine an amount of background light.

16. The method of claim 1, wherein the measuring the third amount of light is used to detect a symbology or the presence of an analyte on the test device.

17. The method of claim 1, further comprising one or more steps selected from the group consisting of:

(1) using the light measurements to correct for light leakage;

(2) reducing the light measurements using a ratiometric formula;

(3) reducing the light measurements using a neural network;

(4) creating a generated image of test data by plotting reduced light measurements;

(5) expressing a generated image as a polynomial mathematical function;

(6) using a curve-fitting algorithm to generate parameters to define a generated image;

(7) optimizing a reconstruction of a generated image and producing a fitted image;

(8) comparing light measurements and fitted image by solving the linear regression;

(9) validating one or more parameters obtained from linear regression and one or more peak heights obtained;

(10) classifying a validated result as positive or negative by comparing peak heights of a clinical sample to reference samples;

(11) classifying a result using a neural network; and

(12) using a test result with other patient information in a decision-support system to generate a medical diagnosis or risk assessment.

18. The method of claim 1, further comprising

emitting the light of the first wavelength from a light emitting diode;

transmitting the emitted light of the first wavelength through a first fiberoptic bundle to the surface of the test device; and

transmitting the second amount of light reflected from the surface of the test device through a second fiberoptic bundle to a photodetector.

19. The method of claim 1, further comprising

emitting the light of the first wavelength from a light emitting diode;

transmitting the emitted light of the first wavelength through a first fiberoptic bundle to the surface of the test device;

transmitting the second amount of light reflected from the surface of the test device through a second fiberoptic bundle to a photodetector;

emitting the light of the second wavelength from a light emitting diode;

transmitting the emitted light of the second wavelength through a third fiberoptic bundle to the surface of the test device; and

transmitting the third amount of light reflected from the surface of the test device through the second fiberoptic bundle to the photodetector.

10. A method for determining a risk or identifying a condition associated with the presence of fetal fibronectin (fFN) in a cervicovaginal sample, comprising:

obtaining a cervicovaginal sample and reacting it with an antibody on a lateral flow test device to produce an image comprising a stripe on the test device indicative of the presence of fFN in the sample;

moving a reader head in a reflectance reader to a position over the test device;

measuring a first amount of light reflected from the surface that comprises the image;

transmitting light of a first wavelength onto the surface at an angle normal to the surface, and measuring a second amount of light reflected normally from the surface;

transmitting light of a second wavelength onto the surface at an angle normal to the surface, and measuring a third amount of light reflected normally from the surface;

repeating each of the moving, transmitting and measuring steps at additional positions on the surface until the surface of the test device that comprises the image is scanned to obtain measurement data indicative of the presence or amount of fFN in the sample.

11. A method for determining a risk or identifying a condition associated with the presence of fetal fibronectin (fFN) in a cervicovaginal sample, comprising:

obtaining a cervicovaginal sample and reacting it with an antibody on a lateral flow test device to produce an image on the test device indicative of the presence of fFN in the sample;

with a reader head in a reflectance reader at a position over the test device, measuring a first amount of light reflected from the position of the surface that comprises the image;

transmitting light of a first wavelength onto the position of the surface at an angle normal to the surface, and measuring a second amount of light reflected normally from the surface;

transmitting light of a second wavelength onto the position of the surface at an angle normal to the surface, and measuring a third amount of light reflected normally from the surface;

moving the reader head in a stepwise fashion to a plurality of positions over the test device, wherein three light measurements are made at each of the plurality of positions, whereby the device is scanned and

and data indicative of the presence or amount of fFN in the sample is obtained.