Optical sensor for detection of free hemoglobin in a whole blood sample

Patent metadata

Field	Value
Publication number	US-11079317-B2
Application number	US-201615776237-A
Country	US
Kind code	B2
Filing date	Nov 17, 2016
Priority date	Nov 18, 2015
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

Sensor for the optical detection of free hemoglobin (96) in a whole blood sample (99), the sensor comprising a translucent slab (2) with a front side (3) and a back side (4) facing away from the front side (3), wherein the front side (3) is adapted for being contacted with a whole blood sample (99); a reflective layer (5) at the front side (3) of the translucent slab (2), the reflective layer (5) being adapted to reflect light reaching the reflective layer (5) from the translucent slab (2); an optical probing device comprising a light source (10) and a detector (20), wherein the light source (10) is adapted to illuminate at least pores in the translucent slab, wherein the detector (20) is arranged to receive light (21) emerging from the pores (6) in response to an illumination (11) by the light source (10), and wherein the detector (20) is adapted to generate a signal representative of the detected light. The translucent slab (2) is provided with dead-end pores (6) extending from the front side (3) into the translucent slab (2) in a direction towards the backside (4). Each of the pores (6) has a respective opening (7) in the front side (3) of the translucent slab (2) penetrating the reflecting layer (5). A cross-sectional dimension of the openings (7) of the pores (6) is dimensioned so as to prevent red blood cells (98) from entering the pores (6), while allowing free hemoglobin (96) to enter the pores (6).

First claim

The invention claimed is:

1. A sensor for the optical detection of a substance in the plasma fraction of a whole blood sample, the sensor comprising:
a translucent slab with a front side and a back side facing away from the front side, wherein the front side is adapted for being contacted with a whole blood sample, wherein the translucent slab comprises pores;
a reflective layer at the front side of the translucent slab, the reflective layer being adapted to reflect light reaching the reflective layer from the translucent slab; and
a light source and a detector configured for optically probing the translucent slab, wherein the light source is adapted to illuminate at least the pores in the translucent slab, wherein the detector is arranged to receive light emerging from the pores in response to an illumination by the light source, and wherein the detector is adapted to generate a signal representative of the detected light;
wherein the pores in the translucent slab are dead-end pores extending from respective openings at the front side, through the reflective layer into the translucent slab, wherein a cross-sectional dimension of the openings of the pores is dimensioned so as to prevent red blood cells from entering the pores, while allowing the substance in the plasma fraction of the whole blood sample to enter the pores.

2. The sensor according to claim 1 , wherein the sensor is adapted for the optical detection of free hemoglobin in a whole blood sample, wherein a cross-sectional dimension of the openings of the pores is dimensioned so as to prevent red blood cells from entering the pores, while allowing free hemoglobin to enter the pores.

3. The sensor according to claim 1 , wherein a cross-sectional dimension of the openings of the pores is about 1 μm or less, about 800 nm or less, about 500 nm or less, or about 400 nm or less, and/or wherein a length of the pores in an axial direction along the pores is less than 100 μm, less than 50 μm, less than 30 μm, or about 25 μm.

4. The sensor according to claim 1 , wherein a porosity of a given volume of the translucent slab comprising pores is between 50% and 5% by volume, between 30% and 10% by volume, or about 15% by volume.

5. The sensor according to claim 1 , wherein an equivalent pore volume depth (DELTA) is less than 20 μm, less than 10 μm, or about 5 μm or less, wherein the equivalent pore volume depth (DELTA) is defined as the total volume of the pores (V) divided by the front side area (A) over which the openings of the pores are distributed.

6. The sensor according to claim 1 , wherein an inner wall surface of the pores is coated with a hydrophilic coating.

7. The sensor according to claim 1 , wherein the light source is configured for providing an obliquely incident illuminating beam from the backside of the translucent slab, wherein an illumination angle is defined as the angle of the incident beam with respect to a surface normal of a reference plane defined by the front side of the translucent slab.

8. The sensor according to claim 1 , wherein the detector is configured to collect light obliquely emerging from the backside of the translucent slab, wherein a detection angle is defined as the angle of the propagation of the emerging light towards the detector with respect to a surface normal of a reference plane defined by the front side of the translucent slab.

9. The sensor according to claim 8 , wherein a plane of incidence and a plane of detection intersect at a surface normal to enclose an azimuthal angle of at least 0 degrees and less than 180 degrees, less than 160 degrees, less than 130 degrees, or about 90 degrees, wherein the plane of incidence is spanned by the direction of the illuminating beam and the surface normal to the reference plane, and wherein the plane of detection is spanned by the direction of the emerging light propagation towards the detector and the surface normal to the reference plane.

10. The sensor according to claim 1 , wherein the translucent slab is provided with further reflective elements arranged inside the pores, in a mouth portion thereof, adjacent to the opening at the front side of the translucent slab.

11. The sensor according to claim 10 , wherein the further reflective elements are provided as a reflective coating covering only a fraction of the circumference of the mouth portion of the pores in the vicinity of the opening, wherein the fraction is about 70% or less or about 50% or less.

12. A system for analyzing a whole blood sample, the system comprising
a sample chamber with inlet and outlet ports for feeding and discharging the whole blood sample;
a first detector adapted to provide a first signal representative of a level of a substance in a plasma phase of the whole blood sample; and
one or more further detectors, each further detector being adapted to provide a respective further signal representative of a blood parameter of the whole blood sample;
wherein the first and further detectors are operable to obtain the first and the one or more further signals from the same whole blood sample, wherein the first detector is configured as a sensor for the optical detection of the substance in the plasma phase of the whole blood sample according to claim 1 .

13. The system according to claim 12 , further comprising a processor configured to provide an output regarding one or more of the further signals based on the first signal.

14. The system according to claim 13 , wherein the output is a correction of the further signal with respect to a detected level of free hemoglobin, a flag indicative of a level of free hemoglobin in the whole blood sample, and/or an instruction to discard one or more of the further signals.

15. A porous mirror for use in the optical detection of free hemoglobin in a whole blood sample, the porous mirror comprising:
a translucent slab with a front side and a back side facing away from the front side, wherein the front side is adapted for being contacted with a whole blood sample; and
a reflective layer applied to the front side of the translucent slab, the reflective layer being adapted to reflect light reaching the reflective layer from the translucent slab;
wherein the translucent slab is provided with dead-end pores extending from respective openings at the front side into the translucent slab, wherein a cross-sectional dimension of the openings of the pores is dimensioned so as to prevent red blood cells from entering the pores, while allowing free hemoglobin to enter the pores.

16. A sensor for the optical detection of a substance in the plasma fraction of a whole blood sample, the sensor comprising:
a translucent article comprising (a) at least one membrane comprising pores and (b) a transparent element with a front side and a back side facing away from the front side, wherein the front side is adapted for being contacted with a whole blood sample;
a reflective layer at the front side of the translucent article, the reflective layer being adapted to reflect light reaching the reflective layer from the translucent article; and
a light source and a detector configured for optically probing the translucent article, wherein the light source is adapted to illuminate at least the pores in the translucent article, wherein the detector is arranged to receive light emerging from the pores in response to an illumination by the light source, and wherein the detector is adapted to generate a signal representative of the detected light;
wherein the pores in the translucent article are dead-end pores extending from respective openings at the front side, through the reflective l

Assignees

• Radiometer Medical Aps

Inventors

• Kjaer Thomas

Classifications

• G01N2015/012

  Red blood cells · CPC title

• G01N15/01

  specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) · CPC title

• G01N21/03

  Cuvette constructions · CPC title

• G01N21/31 Primary

  Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry {(G01N21/72 takes precedence)} · CPC title

• G02B5/0808 Primary

  having a single reflecting layer (G02B5/0883, G02B5/0891 take precedence) · CPC title