Device and method for determining a concentration in a sample

• US 10,416,079 B2
• Filed: 12/18/2014
• Issued: 09/17/2019
• Est. Priority Date: 01/07/2014
• Status: Active Grant

• Current Assignee: Opsolution GmbH
• Original Assignee: Opsolution GmbH
• Inventors: Magnussen, Bjoern, Stern, Claudius, Koecher, Wolfgang
• Primary Examiner(s): Smith, Maurice C
• Application Number:
  US15/109,658
• Publication Number:
  US 20160334332A1
• Time in Patent Office: 1,734 Days
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01N 2021/1782 In-depth resolution
• CPC Class Codes: G01N 2021/4752 Geometry
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2201/06153 the sources being LED's
• CPC Class Codes: G01N 2201/0621 Supply
• CPC Class Codes: G01N 2201/0626 Use of several LED's for spatial resolution
• CPC Class Codes: G01N 2201/0633 Directed, collimated illumination
• CPC Class Codes: G01N 2201/066 Modifiable path; multiple paths in one sample
• CPC Class Codes: G01N 2201/1211 for temperature
• CPC Class Codes: G01N 2201/1214 for humidity

Abstract

A device for optical detection of analytes in a sample includes at least two optoelectronic components. The optoelectronic components include at least one optical detector configured to receive a photon and at least one optical emitter configured to emit a photon. The at least one optical emitter includes at least three optical emitters disposed in a flat, non-linear arrangement, and the at least one optical detector includes at least three optical detectors disposed in a flat, non-linear arrangement. The at least three optical emitters and the at least three optical detectors include at least three different wavelength characteristics.

Claims

1. A device for optical detection of analytes in a sample, the device comprising:

a contact surface that can be brought into contact with the sample or which can be brought into contact with a fluid or a gas that allows photons to pass therethrough so as to get to the sample, and the contact surface comprises at least a first and a second material wherein the first material is at least partially transparent for photons, the second material is either non-transparent or at least less transparent for photons;

at least a first, a second and a third optical emitter that are disposed on a plane as a non-linear arrangement;

at least a first, a second and a third optical detector that are disposed on the plane as a non-linear arrangement;

at least a first pair of optoelectronic components and a second pair of optoelectronic components with each pair of optoelectronic components comprising;

one of the first, second or third emitters and one of the first, second or third detectors, wherein at least one of the optoelectronic components of the second pair is different than the optoelectronic components of the first pair;

wherein,

at least one of the optoelectronic components of the first pair is oriented to dominantly emit or detect photons in a direction which is perpendicular to either the contact surface or the plane on which the optoelectronic components are disposed, and

at least one of the optoelectronic components of the second pair is oriented to dominantly emit or detect photons in a direction which is either,

parallel to the plane on which the optoelectronic components are disposed, or

not parallel to the plane on which the optoelectronic components are disposed and not perpendicular to any of two surfaces which are the contact surface and the plane on which the optoelectronic components are disposed.

2. The device as recited in claim 1, wherein either,

one of the first, second or third emitters is oriented so that the photons which are emitted have a dominant direction of propagation which forms an angle of less than 60 degree with the contact surface, or

one of the first, second or third detectors is oriented so that photons which are detectable have a dominant direction of propagation which forms an angle of less than 60 degree with the contact surface.

3. A device for optical detection of analytes in a sample, the device comprising:

a contact surface that can be brought into contact with the sample or which can be brought into contact with a fluid or a gas that allows photons to pass therethrough so as to get to the sample, and the contact surface comprises at least a first and a second material wherein the first material is at least partially transparent for photons, the second material is either non-transparent or at least less transparent for photons;

at least a first, a second and a third optical emitter that are disposed on a plane as a non-linear arrangement, and the first, the second or the third optical emitter are configured so that their respective emitted photons, directly after passing through the contact surface for the first time after being emitted, comprise a directional characteristic, that describes which quantity of light is emitted in which directions;

at least a first, a second and a third optical detector that are disposed on the plane as a non-linear arrangement, and the first, the second or the third optical detector comprise a directional characteristic, that describes which quantity of light is receivable from which directions, the directions being determined directly before photons pass through the contact surface for the last time before being detected by the respective detector;

at least a first pair of optoelectronic components and a second pair of optoelectronic components with each pair of optoelectronic components comprising;

one of the first, second or third emitters and one of the first, second or third detectors, wherein at least one of the optoelectronic components of the second pair is a different optoelectronic component than the optoelectronic components of the first pair; and

a wavelength characteristic for the first and second pair of optoelectronic components which is defined by that intensity of light for each wavelength of light that the optical emitter of the respective pair emits and which passes through the contact surface into the sample, and that relative portion of the photons that exit the sample and pass through the contact surface at a point and with a direction so they can be detected by the detector, that is detected by the respective optical detector for each wavelength, with the first pair and the second pair having the same wavelength characteristic;

wherein,

the directional characteristic of the emitter of the first pair of optoelectronic components is different from the directional characteristic of the emitter of the second pair of optoelectronic components or the directional characteristic of the detector of the first pair of optoelectronic components is different from the directional characteristic of the detector of the second pair of optoelectronic components or the directional characteristics of both the emitters and the detectors of the first and second pairs are different, and

the directional characteristics of two optoelectronic components are considered different if the quantity of light for the different directions is different, wherein the directions are determined by the angle between the direction of photon propagation and a line perpendicular to the contact surface and the angle between a projection onto the contact surface of direction of photon propagation and a projection onto the contact surface of a straight line connecting the respective optoelectronic component with the other optoelectronic component of the respective pair of optoelectronic components.

4. The device as recited in claim 3, wherein the contact surface comprises surface areas of the transparent material which are each completely surrounded by the non-transparent material in the plane of the contact surface, such that for each optical emitter there is at least one of these surface areas through which photons pass for the first time directly after being emitted by the optical emitter, and such that for each optical detector there is at least one of these surface areas through which photons pass for the last time directly before being detected by the optical detector.

5. The device as recited in claim 4, wherein,

the nontransparent material is arranged so that for at least one of the first and second pairs of optoelectronic components photons must pass through at least one of

the sample, and

the non-transparent material,

to travel from the emitter to the detector.

6. The device as recited in claim 5, wherein,

at least one difference of directional characteristic is achieved by the device having at least one of the optoelectronic components arranged so that it has a nonzero distance to the contact surface, and

by the device having the non-transparent material arranged so that it absorbs at least a fraction of those photons whose directions of propagation are relevant for the directional characteristic so that the directional characteristic does not contain the direction of propagation of the absorbed photons.

7. The device as recited in claim 5, wherein,

at least one difference of directional characteristic is achieved by the device having at least one of the optoelectronic components arranged so that it has a nonzero distance to the contact surface, and

at least one of the following six ways, with

the first way being that at least one of the transparent material and the non-transparent material reflect photons and thus change the photon'"'"'s direction of propagation,

the second way being that at least one of the transparent material and the non-transparent material scatter photons and thus change the photon'"'"'s direction of propagation,

the third way being diffraction of photons to change the photon'"'"'s direction of propagation,

the fourth way being that at least one of the transparent material and the non-transparent material refract photons and change the photon'"'"'s direction of propagation,

the fifth way being absorbing photons and emitting other photons by luminescence, and

the sixth way being that the contact surface of the transparent material is structured so that the transparent material scatters at least a fraction of the photons, thus changing the photon'"'"'s direction of propagation.

8. The device as recited in claim 5, wherein,

the device is configured such that the emitters and detectors comprise semiconductor elements, and

the semiconductor elements are positioned no further than 6 mm from the sample when the device is in its measuring position.

9. The device as recited in claim 6, wherein the device is configured in one of three ways, wherein,

the first way is that at least one of the optoelectronic components has a rectangular geometry,

the second way is that at least one of the contact surface areas has a rectangular geometry, and

the third way is that at least one of the optoelectronic components and at least one of the contact surface areas have a rectangular geometry.

10. The device as recited in claim 9, wherein at least one optoelectronic component is part of two different pairs of optoelectronic components, with the two pairs of optoelectronic components having different directional characteristic, and the difference in directional characteristic is due to the rectangular geometry.

11. The device as recited in claim 10, wherein a line connecting the emitter and the detector of the first of the two different pairs of optoelectronic components intersects a different side of the rectangular geometry than a line connecting the emitter and the detector of the second of the two different pairs of optoelectronic components.

12. The device as recited in claim 3, wherein,

at least one of the optoelectronic components has an optical orientation which is not perpendicular to the plane on which the optoelectronic components are disposed,

the optical orientation of the first, second or third emitter is defined as the dominant direction into which photons are emitted, and

the optical orientation of the first, second or third detector is defined as the dominant direction from which photons are detected when the detector is illuminated evenly from all directions.

13. The device as recited in claim 8, wherein,

the non-transparent material and the transparent material are arranged in at least one of the following two ways,

the first way being arranged so that all the photons emitted by at least one optical emitter propagate in directions within a range of 5 degrees to 175 degrees to an irradiation surface of the optical emitter, wherein the directions of propagation of the photons are determined directly after the photons pass through the contact surface for the first time after being emitted, and

the second way being arranged so that all the photons detected by at least one optical detector propagate in directions within a range of 5 degrees to 175 degrees to a detection surface of the optical emitter, wherein the directions of propagation of the photons are determined directly before the photons pass through the contact surface for the last time before being detected.

21. The device as recited in claim 8, wherein,

the first pair of optoelectronic components has a distance between the emitter and detector of the pair so that the said distance is equal to the distance between the emitter and detector of the second pair of optoelectronic components.

22. The device as recited in claim 8, wherein,

the first pair of optoelectronic components has a distance between the two optoelectronic components of the pair so that the said distance is different from the distance between two optoelectronic components of at least one other pair which has the same wavelength characteristic as the first pair of optoelectronic components.

23. The device as recited in claim 8, further comprising:

two additional pairs of optoelectronic components, each comprising an emitter and a detector, and each having a wavelength characteristic which is defined in the same way as for the first and second pair, and

the first pair, the first additional pair and the second additional pair having mutually different wavelength characteristics.

24. The device as recited in claim 3, further comprising:

at least two detectors having mutually different wavelength characteristics and at least two emitters having mutually different wavelength characteristics;

wherein,

the wavelength characteristics of the at least two detectors and the wavelength characteristics of the at least two emitters each have a wide enough spectral bandwidth, such that there are combinations of emitters and detectors that have a resulting wavelength characteristic that results from the combination of the wavelength characteristic of the emitter and the wavelength characteristic of the detector;

the number of such resulting wavelength characteristics that are mutually different from each other is larger than the number of mutually different wavelength characteristics of all of the detectors, and

the number of such resulting wavelength characteristics that are different from each other is larger than the number of different wavelength characteristics of all of the emitters.

25. The device as recited in claim 5, wherein,

at least two optoelectronic components are disposed so that photons that interact with both, the sample and the optoelectronic components, have to pass through the same surface area of the contact surface, wherein said surface area of the contact surface is completely surrounded by non-transparent material,

the at least two optoelectronic components are constituted in exactly one of two ways, wherein the first way is that the two optoelectronic components include at least two optical detectors, and wherein the second way is that the two optoelectronic components include at least two optical emitters, and

at least two of the at least two optoelectronic components have a different wavelength characteristic.

14. A method for optical detection of analytes in a sample comprising:

using at least three emitters to emit photons into the sample so that the photons travel through the sample and interact with the sample in at least one of three ways, the first way is photons get scattered by the sample, the second way is photons get absorbed by the sample and the third way is the photons initiate luminescence;

using at least three detectors to detect at least a part of the photons which exit from the sample;

using at least a first measurement combination of one of the at least three emitters and one of the at least three detectors, and a second measurement combination of one of the at least three emitters and one of the at least three detectors, wherein at least one of the emitter and the detector of the second measurement combination is not the emitter or the detector of the first measurement combination,

wherein,

each of the first and second measurement combinations, are configured such that photons are generated as a result of activating the respective emitter of the measurement combination, and the photons propagate through the sample, and a portion of the photons are detected by the respective detector of the measurement combination and have a spatial probability of being present in a volume in the sample, and

there is a difference between the spatial probability of the portion of the photons for the first measurement combination and the spatial probability of the portion of the photons for the second measurement combination, which has the effect of a larger amount of information on the analyte in the sample being available than from a single measurement combination; and

selecting directional characteristics that cause the difference in the spatial probability of photons of a specific wavelength between the first measurement combination and the second measurement combination,

wherein,

the directional characteristic for each emitter describes how many photons propagate in which directions directly before they enter the sample, and

the directional characteristic for each detector describes what portion of arriving photons the respective detector is capable of detecting from which directions, with the directions being determined directly after photons exit the sample.

15. The method as recited in claim 14, wherein,

a first measurement result is generated by activating the emitter of the first measurement combination and measuring the number of photons which are detected by the detector of the first measurement combination,

a second measurement result is generated by activating the emitter of the second measurement combination and measuring the number of photons which are detected by the detector of the second measurement combination, and

using a mathematical formula that computes the concentration of the analyte in the sample from at least the first and second measurement result.

16. The method as recited in claim 15, wherein there is a depth for which the probability of presence in a distance less than this depth from the sample surface for photons that were measured to obtain the first measurement result is higher than the respective same probability calculated for the photons that were measured to obtain the second measurement result.

17. The method as recited in claim 16, wherein,

additional measurement combinations are used to generate additional measurement results,

the first measurement result, the second measurement result, and the additional measurement results are used to compute the concentration of the analyte in the sample, and

the computation involves calculating at least one property of the sample as a function of depth below a point on a surface of the sample.

18. The method as recited in claim 16, further comprising:

using a third measurement combination of one of the at least three emitters and one of the at least three detectors,

wherein,

the first and second measurement combination have the same distance between emitter and detector, and

the third measurement combination has a distance between emitter and detector which is different from the respective distances of the first and the second measurement combination.

19. The method as recited in claim 14, further comprising:

using at least two of the emitters that each, when activated, emits photons over an emission range of wavelengths with an emitter specific intensity for each wavelength;

using at least two detectors which each, when activated, measures a single light intensity signal that represents photons that were detected over a detection wavelength range with a detector specific detection probability for photons of each wavelength;

activating the emitters in succession and activating at least two detectors to detect photons which were emitted and traveled through the sample, and

selecting the emission wavelength ranges and detection wavelength ranges so, that for at least two emitters with mutually different emission range there are at least two detectors with mutually different detection range, which are each capable of detecting photons emitted by the activated emitter;

selecting the emitters and detectors, such that there is overlap between the emitter wavelength ranges and detector wavelength ranges for a number of measurement combinations; and

selecting the emitters and detectors so, that there are more mutually different wavelength characteristics of measurement combinations for the detection of an analyte in a sample than the sum of the number of mutually different emission ranges of the emitters and the number of mutually different detection ranges of the detectors,

wherein, for each combination of an emitter and a detector, a wavelength characteristic for that emitter-detector measurement combination is defined as the normalized product of the emission intensity and the detection probability for each wavelength.

20. The method as recited in claim 15, further comprising:

recording the measurement values multiple times in succession.