Determining time response value of an analyte in a liquid

Patent metadata

Field	Value
Publication number	US-12379307-B2
Application number	US-202118258579-A
Country	US
Kind code	B2
Filing date	Dec 20, 2021
Priority date	Dec 22, 2020
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

There is presented an apparatus for determining one or more time response values of an analyte or a group of analytes ( 96 ) in a liquid ( 99 ) comprising a translucent element comprising pores ( 6 ), wherein the pores ( 6 ) are dead end pores ( 6 ) extending into the translucent element from respective openings ( 7 ) in the translucent element, wherein a cross-sectional dimension of the openings ( 7 ) of the pores ( 6 ) is dimensioned so as to prevent larger particles or debris from entering the pores ( 6 ), while allowing the analyte or the group of analytes in the liquid ( 99 ) to enter the pores ( 6 ) via diffusion, one or more light sources ( 10 ) being adapted to illuminate at least the pores ( 6 ) in the translucent element ( 2 ), and a light detector ( 20 ) being adapted to at each of multiple points in time receive light ( 21 ) emerging from the pores ( 6 ) in response to illumination ( 11 ) by the one or more light sources, wherein the light detector is further adapted to generate one or more signals based on the received light, each of the one or more signals being temporally resolved and representative of at least a part of the received light, and wherein the apparatus is further comprising a data processing device comprising a processor configured to determine one or more time response values based on the one or more signals.

First claim

The invention claimed is:

1. A method for determining a difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid comprising providing:
i. a translucent element comprising pores, wherein the pores are dead end pores extending into the translucent element from respective openings in the translucent element, wherein a cross-sectional dimension of the openings of the pores is dimensioned so as to prevent larger particles or debris from entering the pores, while allowing the two or more predetermined analytes in the liquid to enter the pores via diffusion,
ii. one or more light sources, and
iii. a light detector,
contacting the pores of the translucent element with the liquid,
illuminating with the one or more light sources at least the pores in the translucent element,
at each of multiple points in time receiving light emerging from the pores in response to the illumination,
generating one or more signals based on the received light, each of the one or more signals being temporally resolved and representative of at least a part of the received light,
determining one or more time response values based on the one or more signals, and
determining a difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid based on the one or more time response values.

2. The method according to claim 1 , wherein the two or more predetermined analytes are cell-free hemoglobin not bound to haptoglobin and haptoglobin-bound hemoglobin.

3. The method according to claim 2 , further comprising:
determining a presence of a hemoglobin-haptoglobin complex based on the difference measure, and/or
determining an absence of a hemoglobin-haptoglobin complex based on the difference measure.

4. The method according to claim 1 , further comprising:
contacting the apparatus with a reference liquid so as to fill the pores with the reference liquid, and/or waiting for a diffusion time to allow for diffusion of the two or more predetermined analytes in the liquid into the pores to reach a steady state.

5. The method according to claim 1 , wherein the method further comprises providing:
a data processing device comprising a processor configured to carry out one or more of the following:
controlling the one or more light sources to illuminate at least the pores in the translucent element,
controlling the detector to at each of multiple points in time receive light emerging from the pores in response to the illumination,
receiving one or more signals based on the received light, each of the one or more signals being temporally resolved and representative of at least a part of the received light,
determining the one or more time response values based on the one or more signals, and
determining the difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid based on the one or more time response values.

6. The method according to claim 1 , wherein the method further comprises obtaining a plurality of signals for different wavelength intervals.

7. The method according to claim 1 , wherein
determining the difference measure indicative of a difference in concentration between the two or more predetermined analytes is based on a plurality of time response values obtained for different wavelength intervals.

8. The method according to claim 1 , wherein
determining the difference measure indicative of a difference in concentration between the two or more predetermined analytes is based on a plurality of time response values.

9. The method according to claim 8 , wherein the difference measure indicative is a ratio between a time response value obtained for a first wavelength interval that is 415 nm and a time response value obtained for a second wavelength interval that is 450 nm.

10. The method according to claim 1 , wherein the one or more time response values are:
based on one or more differences in signal values within each of the one or more signals where said signal values are obtained at different points in time, and/or is one or more characteristic times.

11. The method according to claim 1 , further comprising
determining a concentration of cell-free hemoglobin not bound to haptoglobin and/or a concentration of haptoglobin-bound hemoglobin.

12. The method according to claim 11 , wherein a determined concentration of an analyte in the liquid is adjusted based on the one or more time response values.

13. An apparatus for determining a difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid, comprising
a translucent element comprising pores, wherein the pores are dead end pores extending into the translucent element from respective openings in the translucent element, wherein a cross-sectional dimension of the openings of the pores is dimensioned so as to prevent larger particles or debris from entering the pores, while allowing the two or more predetermined analytes in the liquid to enter the pores via diffusion,
one or more light sources being adapted to illuminate at least the pores in the translucent element, and
a light detector being adapted to at each of multiple points in time receive light emerging from the pores in response to an illumination by the one or more light sources,
wherein the light detector is further adapted to generate one or more signals based on the received light, each of the one or more signals being temporally resolved and representative of at least a part of the received light, and wherein the apparatus further comprises
a data processing device comprising a processor configured to
determine one or more time response values based on the one or more signals, and
determine a difference measure indicative of a difference, in concentration between two or more predetermined analytes in a liquid based on the one or more time response values.

14. The apparatus according to claim 13 , wherein the two or more predetermined analytes are cell-free hemoglobin not bound to haptoglobin and haptoglobin-bound hemoglobin, such as a hemoglobin-haptoglobin complex.

15. The apparatus according to claim 13 or 14 , wherein the one or more light sources and/or the light detector are operatively coupled to the data processing device comprising a processor, and wherein the data processing device comprising a processor is further arranged to
obtain a plurality of signals for different wavelength intervals,
determine a plurality of time response values by determining for each of the signals within the plurality of signals a time response value, and
determine the difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid based on the plurality of time response values.

16. The apparatus according to claim 15 , wherein the data processing device is further configured to:
determine an adjusted time response value, wherein the adjusted time response value is determined based on at least two time response values within the plurality of time response values, and
determine the difference measure indicative of a difference in concentration between two or more predetermined analytes in a liquid based on the adjusted time response value.

17. The apparatus according to claim 13 , wherein the one or more light sources and/or the light detector are operatively coupled to the data processing device comprising a processor, and wherein the data processing device comprising a processor is further arr

Assignees

• Radiometer Medical Aps

Inventors

• Kjaer Thomas

Classifications

• G01N2021/1789

  Time resolved · CPC title

• G01N2021/0346

  Capillary cells; Microcells · CPC title

• G01N21/55

  Specular reflectivity · CPC title

• G01N21/6408

  with measurement of decay time, time resolved fluorescence · CPC title

• G01N21/552

  Attenuated total reflection · CPC title