CN111936049A

CN111936049A - Measurement system for spectroscopic biopsy

Info

Publication number: CN111936049A
Application number: CN201980023664.0A
Authority: CN
Inventors: 赵玉京; 金允玉
Original assignee: 1 Flor
Current assignee: 1 Flor
Priority date: 2018-03-29
Filing date: 2019-03-29
Publication date: 2020-11-13
Also published as: WO2019185903A1; EP3773206A1

Abstract

The invention relates to a measuring system (1) for the spectroscopic examination of living tissue, comprising a housing (2) having two housing openings (2a, 2b) on one side of the housing, an optical radiation source (3) arranged in the housing (2), and an optical radiation detector (4) arranged in the housing (2), wherein the radiation source (3) and the optical radiation detector (4) are each associated with one housing opening (2a, 2b), wherein an optical connection is present between the radiation source (3) and the radiation detector (4) within the housing (2). The object of the invention is to minimize internal and external interference influences and/or to be able to be detected and thus to be reliably taken into account when evaluating measurement results, wherein the measurement system can be used flexibly for different persons and application sites and should be able to be integrated into further measurement systems. To this end, the invention proposes that an optical reference sensor (6) is arranged in the housing (2), and that a direct optical connection channel (2c) for transmitting a reference signal is present from the radiation source (3) to the reference sensor (6).

Description

Measurement system for spectroscopic biopsy

Technical Field

The invention relates to a measuring system for spectroscopic examination of living tissue, comprising a housing with two housing openings on one side of the housing, one or more optical radiation sources arranged in the housing, and one or more optical radiation detectors arranged in the housing, wherein the radiation sources and the optical radiation detectors are each associated with a housing opening, wherein no optical connection exists between the radiation sources and the radiation detectors inside the housing. Furthermore, the invention relates to a method for using a measuring system.

Background

Spectroscopic examination of living tissue enables the observation of static and dynamic tissue properties and their associated physiological processes. Examples of known applications of spectroscopic methods in the analytical and medical fields are the oxygen-metering and/or spectroscopic determination of different physiological parameters of humans.

Typical measuring systems for the mentioned applications have one or more radiation sources and one or more radiation detectors. Specific examples of radiation sources and radiation detectors are LEDs and photodiodes. A radiation source irradiates the tissue to be examined and a beam emitted by the radiation source is received, scattered, reflected or transmitted by the tissue. The radiation detector is here intended to measure absorption, reflection and/or transmission properties of the tissue. US 2016/0061726 a1, for example, discloses such a measuring system.

In an ideal case, the change in the measured signal is due solely to a change in the physiological characteristics of the examined tissue. However, other factors of the measuring system, such as environmental parameters or operating conditions, can influence the detected measuring signal in the actual measurement. Just as the physiological characteristic may be a change of the measurement signal of a dynamic nature, for example when the radiation source heats up during operation and thereby changes the intensity of the emitted beam.

The changes related to the measurement system, but not related to physiological changes of the tissue, have to be minimized in order to obtain reliable and error-free measurements. Otherwise the accuracy and precision of the measurement is deteriorated.

Disclosure of Invention

The object of the present invention is therefore to further develop the measuring system mentioned at the outset in such a way that internal and external interference influences are minimized and/or can be detected and can therefore be reliably taken into account when evaluating the measurement results and non-invasively determining at least one physiological parameter, wherein the measuring system can be used flexibly for different persons and application sites and furthermore should be able to be used as a module in a superordinate measuring system. Therefore, not only a compact structure, applicability to different tissue surfaces and easy cleaning are desirable in order to meet the hygiene requirements in the medical field.

In order to solve this problem, the invention proposes, starting from a measuring system of the type mentioned at the outset, that an optical reference sensor is arranged in the housing and that a direct optical connection channel for transmitting a reference signal is present from the radiation source to the reference sensor.

As a result, a largely interference-free reference value can be determined simultaneously and continuously with respect to the measured values of the radiation detector by means of the reference sensor and can be used to evaluate the measurement results. The fluctuations in the intensity of the radiation source caused by the operation can thus be filtered out and no longer distort the measurement results for analyzing the tissue.

Expediently, the inner surface of the housing is provided with a light-absorbing black layer. By means of this measure, the radiation beam emitted into the tissue is not influenced by reflection and scattering on the inner wall of the housing. Furthermore, the probability that light reflected back by the tissue into the housing can reach the reference sensor by reflection and scattering on the wall is thereby reduced.

It is particularly advantageous if the housing opening is covered with an at least partially transparent layer. This prevents dirt from entering the housing. Furthermore, the tissue-contacting surface of the housing can be cleaned particularly easily. The measurement itself is mostly not substantially affected by the layer formed in a transparent manner.

In a further advantageous embodiment of the invention, the transparent layer has a filter element. The transparent layer can be designed, for example, such that it is transparent only in one direction. A defined optical radiation path can thereby be forced, for example to avoid a reflection of the beam from the tissue back to the radiation source.

It is also expedient for the measuring system to have one or more temperature sensors. The temperature sensor may for example implement an NTC thermistor. By means of these measures, further interference influences can be compensated and/or more accurately classified. For example, the influence of heating of the measuring system due to the tissue to be contacted and due to the surrounding environment can be taken into account. In order to achieve a measurement result particularly suitable for examining physiological parameters, it is expedient if the radiation source is provided for emitting a radiation beam in the visible and/or near infrared wavelength range. Particularly effective measurement results can be achieved by means of the radiation beam in the wavelength range. While not damaging the tissue.

It is particularly advantageous if the ratio of the height of the connecting channel to the distance between the radiation source and the housing opening, in which the radiation source is arranged, is at most 0.5. This further ensures that the reference sensor measures only the radiation beam of the radiation source and does not measure the incident ambient light or the light reflected back from the tissue.

A further advantageous embodiment provides that the housing is designed as a flexible band, for example. Thereby, the measurement system can be flexibly adapted to different tissue surface structures. The miniaturized measuring system may for example be integrated into a bracelet or a ring or ring-like shape. A direct optical connection between the radiation source and the reference sensor can be realized, for example, by means of a fiber optic cable, so that a reference measurement of the radiation intensity is also possible, for example, if no straight light path exists between the radiation source and the reference sensor in this embodiment.

In particular in configurations with flexible bands and thus adaptation to different tissue structures, it is likewise possible for the miniaturized measuring system to be moved over different tissue types or body parts and to receive measurement data continuously there, for example in order to check differences between the tissue types.

Drawings

The present invention is described in detail below with reference to the accompanying drawings. In the drawings:

fig. 1 schematically shows a measuring system according to the prior art;

fig. 2 schematically shows a cross-sectional view of a measuring system according to the invention in a first embodiment;

fig. 3 schematically shows a cross-sectional view of a measuring system according to the invention in a second embodiment;

fig. 4 schematically shows a cross-sectional view of a measuring system according to the invention in a third embodiment;

fig. 5 schematically shows a cross-sectional view of a measuring system according to the invention in a fourth embodiment;

fig. 6 schematically shows a cross-sectional view of a measuring system according to the invention in a fifth embodiment;

fig. 7 schematically shows a cross-sectional view of a measurement system according to a sixth embodiment of the invention.

Detailed Description

A measuring system known from the prior art is shown in fig. 1 with the reference numeral 1. The measuring system 1 has a housing 2, a radiation source 3 and a radiation detector 4. The measuring system 1 is used for spectroscopic examination of a living tissue 5. In reflection spectroscopy, the radiation source 3 and the radiation detector 4 are generally located in a plane parallel to the tissue 5 to be examined, as shown in fig. 1. For example one or more LEDs may be used as radiation source 3 and a photodiode may be used as radiation detector 4. The housing 2 has two

housing openings

2a, 2b on its side facing the tissue 5, through which the radiation beam can exit the housing 2 and enter the housing.

As can be seen in fig. 1, there is no direct path of the beam of the radiation source 3 to the radiation detector 4. If disturbing influences, such as ambient light, are neglected, the light detected by the radiation detector 4 must therefore propagate through the tissue 5. Accordingly, the signal of the radiation detector 4 contains information about the optical properties of the irradiated tissue 5.

The main difference and advantage of this measuring system 1 over other known alternative measuring systems which measure only diffuse reflection, for example only transmission, is that the measuring system 1 can in principle be applied on any part of the body, since there are no geometrical restrictions, for example, with respect to the thickness of the tissue 5 to be examined. Possible paths of the beam through the tissue 5 from the radiation source 3 to the radiation detector 4 are indicated by directional arrows in the tissue 5.

However, a disadvantage of this measuring system 1 is that it is considerably more difficult to determine the intensity of the radiation source 3 than, for example, a transmission-based measuring system 1: since in the measuring system 1 shown in fig. 1 there is no direct light path from the radiation source 3 to the radiation detector 4, there is no possibility of determining the radiation intensity for measuring tissue with the aid of the existing radiation detector 4. In the measuring system shown in fig. 1, the measurement of the radiation intensity is possible only when using other external aids, for example reflectors, and only before or after the measurement of the tissue 5. However, this solution complicates the measuring system 1 and furthermore does not allow time-dependent intensity fluctuations of the radiation source 3 to be detected during the measurement.

Fig. 2 schematically shows a first embodiment according to the present invention. An optical reference sensor 6 is arranged in the housing 2. The reference sensor 6 is provided for continuously measuring the radiation intensity of the radiation source 3 during the measuring process. For this purpose, a connecting channel 2c is provided between the radiation source 3 and the reference sensor 6. The connecting channel 2c is designed in such a way that the measured optical signal is influenced by as little external interference as possible, in particular in such a way that no incident external light or light reflected by the tissue back to the radiation source influences the measured optical signal. During the measurement process, the radiation detector 4 and the reference sensor 6 are read in parallel. In this way, a simultaneous determination of the tissue properties and the radiation power of the radiation source 3 can be achieved. The signal of the radiation detector 4, which measures the tissue properties, can then be normalized on the basis of the signal of the reference sensor 6, so that fluctuations in the radiation intensity of the radiation source 3, for example due to temperature changes, can be compensated.

The reference sensor 6 can be located between the radiation source 3 and the radiation detector 4 as shown in fig. 2, however this is not absolutely required and further positioning of the reference sensor is possible, furthermore a connecting channel between the radiation source 3 and the reference sensor 6 is realized.

In principle, not only the number of radiation sources 3, radiation detectors 4 and reference sensors 5, but also their arrangement can be adapted to the respective requirements. A main aspect that is important for the design of the measuring system is the distance between the radiation source 3 and the radiation detector 3, since the typical penetration depth of the beam into the tissue, which reaches the detector, is predetermined by this distance. If not only tissue layers close to the surface but also layers at deeper positions are to be examined, a certain spacing between the radiation source 3 and the detector 4 is required. In this case, the illustrated embodiment of the invention makes particularly efficient use of the space occupied by the measuring system and thus makes a particularly compact design possible, since the reference sensor 6 can be placed between the radiation source 3 and the radiation detector 4 in a space-saving manner.

Instead of LEDs, it is also possible, for example, to use lasers (for example in the form of laser diodes) as radiation source 3. The geometrical arrangement of the radiation sources 3 inside the module is likewise not fixed. The radiation sources 3 can be arranged, for example, in a row, in a plurality of rows (matrix), or in a semicircular manner. Instead of photodiodes, detector arrays or CMOS sensors can also be used as radiation detector 4 and reference sensor 6. In the case of a plurality of radiation detectors 4, they can be used in different arrangements, for example linearly, in a matrix or circularly.

Fig. 3 shows a measuring system 1 according to the invention in a second embodiment. In this embodiment, the radiation detector 4 and the radiation source 3 are located in a Printed Circuit Board (PCB)7 in the measurement system 1. The housing 2 is arranged in the PCB 7. The housing has two

cavities

8a, 8 b.

A plurality of LEDs 3a as radiation sources 3 and a photodiode as reference sensor 6 are arranged on the PCB 7. The LED3a and the reference sensor 6 are furthermore arranged jointly in the cavity 8 a. Light can be injected into the cavity 8a or emitted from the cavity 8a through the housing opening 2a of the housing 2. In order to protect the measurement of the reference sensor 6 from incident ambient light or light reflected back from the tissue, a separating body 9 is provided, by means of which a narrow optical connection channel 2c between the radiation source 3 and the reference sensor 6 is formed. The height H of the optical connection channel 2c is an important system parameter. The height H must be much smaller than the spacing a between the LED3a and the housing opening 2a, since otherwise the light reflected back from the tissue 5 to the LED3a can also reach the reference sensor 6. It is expedient for this purpose to design the optical connection channel 2c as narrow as possible. Preferably, the ratio of the height H of the connecting channel 9 to the distance a between the LED3a and the housing opening 2a is at most 0.5. In the embodiment shown here, this ratio is about 0.38.

Furthermore, the housing 2 and in particular the walls of the

cavities

8a, 8b are painted black, so that incident ambient light is not reflected at said walls or scattered in the cavity 8 a. For this reason, the PCB 7 is also coated with a black protective lacquer, since this also ensures very good absorption of light due to its color.

Furthermore, the radiation detector 4 is arranged on the PCB 7. The radiation detector is located in the cavity 8 b. Light can be injected into the cavity 8b through the housing opening 2b or can exit the cavity 8 b.

A flexible cable 10 is provided on the back of the PCB 7 through which the LED3a is supplied with current or control and the

detectors

4, 6 can be read.

The

housing openings

2a, 2b of the

cavities

8a, 8b are provided with

windows

11a, 11b, which are made of a transparent material. The

windows

11a, 11b are separated from each other by a light-impermeable material 12, so that it is prevented that the light of the LED3a can be reflected multiple times inside the window and reach the radiation detector 4 without passing through the tissue 5. Since the

windows

11a, 11b can clean the side of the housing 2 that is in contact with the tissue 5 particularly easily.

Preferably, biocompatible materials are used for the housing 2, the

windows

11a, 11b and the light-impermeable material 12, by means of which the

windows

11a, 11b are connected, since the abutment face of the module is thus biocompatible with respect to the living tissue 5.

The PCB 7 used is in this embodiment much larger than the housing 2. The projecting part of the PCB can be used to fix the measuring system 1 in a measuring device, not shown here, by means of an adhesive or a screw. When selecting the further fixing possibilities, the size of the PCB 7 can also be reduced to the size of the housing 2.

The measurement system 1 shown in this embodiment is very compact in size. The housing 2 is only 3.8mm high and 7.5mm wide. The PCB 7 is 12.5mm wide, so that the measuring system 1 can be integrated particularly well into a superordinate measuring instrument due to its compactness.

During the measurement, the measurement system 1 is placed onto the tissue 5 such that the

housing openings

2a, 2b are directed towards the tissue 5. The LED3a is then controlled by a measurement control and regulation unit (MSR unit, not shown here) via a flexible cable 10, and the LED3a emits the beam into the cavity 8 a. A first part of the beam is conducted into the tissue 5 through the housing opening 2a and the window 11a, and a second part of the beam reaches the reference sensor 6 on a direct path. The remaining beams are substantially absorbed due to the black coating on the walls of the cavity 8a or on the PCB 7. The radiation beam emitted into the tissue 5 propagates in the tissue and is reflected a plurality of times. A part of the beam finally passes through the window 11b and the housing opening 2b into the cavity 8b and can be detected there by the radiation detector 4. The beam measured by the radiation detector 4 is detected by the MSR unit. The MSR unit likewise detects the values measured by the reference sensor 6 and can finally take these into account when evaluating the overall examination.

The third exemplary embodiment shown in fig. 4, as an extension of the exemplary embodiment shown in fig. 3, has an optical filter element on the

windows

11a, 11b facing the

cavities

8a, 8b and an optical filter element in the optical connection channel 2c between the LED3a and the reference sensor 6.

The optical filter element 13 may be, for example, an interference filter or an interference mirror comprising an antireflection film for a determined wavelength or wavelength range. In the case of

windows

11a, 11b, the filter element 13 may also be integrated directly into the

windows

11a, 11 b. The filters or mirrors can influence which subelement of the measuring system 1 into which a beam of a specific wavelength or wavelength range can be injected or from which a beam can emerge. Thereby, disturbances, for example due to ambient light, undesired diffuse reflection of light from the tissue 5 into the cavity 8a or thermal radiation (infrared) of the tissue 5 into the

cavities

8a, 8b, can be reduced. The filtering function is illustrated by the directional arrows at the filter elements 13.

In a fourth exemplary embodiment, in fig. 5, the measuring system 1 is supplemented by a further radiation detector 4a, so that the measuring system 1 can also carry out transmission measurements by means of said further radiation detector. In the transmission measurement, the radiation power of the radiation source 3 measured by the reference sensor 6 can likewise be taken into account. It is pointed out that in this exemplary embodiment, although the intensity of the LED3a can in principle be determined by the further radiation detector 4a, this cannot be carried out in parallel with the measurement of the tissue 5. The use of a separate reference sensor 6 is therefore also particularly advantageous in this embodiment.

Fig. 6 shows a fifth embodiment according to the invention. The invention is integrated in a previous measuring device, which has two

side parts

2c, 2 d. Furthermore, a total of three

temperature sensors

14a, 14b, 14c are integrated into the measuring assembly, two of which are integrated directly into the measuring system 1. An NTC thermistor, for example, can be used as the temperature sensor 14. Additional temperature sensors 14 can be used both inside and outside the measuring system 1 in order to compensate for other interference influences or to classify them more accurately (for example, by the influence of the tissue 5 being contacted and by the surrounding environment causing the measuring system 1 to heat up). The temperature of the tissue to be contacted can in particular be measured directly by the temperature sensor 14 c.

For the purpose of illustration, the measuring system 1 in fig. 6 is designed for examining a finger 5 a: a temperature sensor 14a is arranged in the cavity 8a, so that the temperature of the surroundings of the LED3a and the radiation detector 4 can be determined. It should be noted that fig. 6 is only a cross-sectional view and that the temperature sensor 14a is located on the edge of the housing, so that the channel between the LED3a and the reference sensor 6 remains largely unoccupied and thus does not negatively affect the reference measurement. The temperature measured by the temperature sensor 14a has a plurality of causes (heat radiation of the finger, heat conduction between the finger 5a and the housing 2, heat radiation of the LED3a, heating of the housing 2 due to operation of the electronic components). These reasons can be further differentiated by further temperature sensors, for example, by an additional temperature sensor 14b, which measures only the housing temperature, being inserted into the housing wall. If, in addition, a temperature sensor 14c is arranged outside the measuring system 1 for directly measuring the temperature (thermal conduction) on the finger 5a, the finger temperature can be determined directly and thus additional information can be obtained about the heat source present in the system.

Fig. 7 shows a sixth embodiment, in which the measuring system 1 with a flexible printed circuit (FPC 16) is implemented and integrated into a ring 17, in which living tissue 5, for example a human finger, is located. The main difference to the preceding exemplary embodiment is that the components of the measuring system do not lie in a plane but are oriented along a circular arc, wherein further geometries (oval segments, etc.) can also be realized by the FPC 16. If the FPC 16 is bent to such an extent that there is no straight optical path between the LED3a and the reference sensor 6, the optical conductor 15 may be used to transmit an optical signal. The main feature of the sixth exemplary embodiment is that the measuring system 1 in this embodiment can be permanently worn on the body and can thus be measured continuously or separately, for example, at certain time intervals. A comparable embodiment can be realized, for example, in the form of a bracelet. The invention enables different operating modes for the LEDs 3a used in the measuring system 1. The LED3a may be operated, for example, in any multiplexing method or modulation method. The signals measured at the radiation detector 4 and the reference sensor 6 can then be analyzed by a corresponding demultiplexing method or demodulation method. A specific example for the method is the sequential activation of different LEDs 3a within a defined time period or the pulsed operation of a plurality of LEDs 3a in parallel, wherein the pulse frequency for the individual LEDs 3a is different.

The

cavities

8a, 8b in the housing 2 can be filled with ambient air, in which the radiation detector 4, the reference sensor 6 and the radiation source 3 are located, which is enclosed during the manufacturing process. Alternatively, the

cavities

8a, 8b may contain a gas, a gas mixture or a solid material, such as epoxy, that is introduced during the manufacturing process. In the case of a solid material, only a part of the

cavities

8a, 8b or the individual optical elements may also be encapsulated with a solid material, for example epoxy resin, in order to protect the elements. For filling the cavity, a porous material that is water-proof with nitrogen and subsequently extruded can likewise be used.

List of reference numerals

1 measuring system

2 casing

2a, b housing opening

2c optical connection channel

2d, e side part of the housing

3, 3a radiation source, LED

4, 4a radiation detector

5 tissue of

6 reference sensor

7 Printed Circuit Board (PCB)

8a, b cavity

9 spacer

10 cable

11a, b window

12 light-impermeable material

13 Filter element

14a, b, c temperature sensor

15 optical conductor

16 FCP

17 annular element

A (of the LED3a and the housing opening 2 a) distance

Height of H optical connection channel 2c

Claims

1. Measuring system (1) for spectroscopic examination of living tissue, having a housing (2) with two housing openings (2a, 2b) on one side of the housing (2), at least one optical radiation source (3) arranged in the housing (2) and at least one optical radiation detector (4) arranged in the housing (2), wherein the radiation source (3) and the optical radiation detector (4) are each assigned to one housing opening (2a, 2b), wherein there is no optical connection inside the housing (2) between the radiation source (3) and the radiation detector (4),

it is characterized in that the preparation method is characterized in that,

an optical reference sensor (6) is arranged in the housing (2), and a direct optical connection channel (2c) for transmitting a reference signal is present from the radiation source (3) to the reference sensor (6).

2. The measuring system (1) as claimed in claim 1, having a compact, miniaturized design which enables it to be used as a component of a further superior measuring system, in particular a portable measuring system, for the field of analysis and medical applications.

3. The measuring system (1) according to any one of the preceding claims, characterized in that the height (H) of the connecting channel (2c) between the radiation source (3) and the reference sensor (6) is at most half the distance (a) of the radiation source (3) from a housing opening (2a, 2b) to which the radiation source (3) is assigned.

4. The measurement system (1) according to any one of claims 1-3, a signal measured by the reference sensor (6) being usable for detecting fluctuations in the intensity of the radiation source (3) and thereby improving the measurement accuracy and accuracy of one or more physiological parameters.

5. The measurement system according to any of the preceding claims, characterized in that the measurement system (1) comprises one or more temperature sensors (14a, 14b, 14 c).

6. The measuring system (1) according to any one of the preceding claims, characterized in that the housing (2) is configured as a flexible belt.

7. A measuring system according to claim 1, characterized in that the surface of the housing (2) is provided with a black layer.

8. The measuring system according to any of the preceding claims, wherein the housing opening (2a, 2b) is covered with an at least partially transparent layer.

9. A measuring system according to claim 3, characterized in that the transparent layer comprises an optical filter element (13).

10. The measuring system according to any of the preceding claims, characterized in that the optical radiation source (3) is arranged in a cavity (8a) and the radiation detector is arranged in a further cavity (8b), and that these cavities (8a, 8b) are filled with a gas, a mixed gas containing ordinary ambient air, or a solid material, such as epoxy resin.

11. The measuring system (1) according to any one of the preceding claims, characterized in that the radiation source (3) is arranged for emitting a beam in the visible and/or near infrared wavelength range.

12. Method for examining living tissue (5) using a measurement system (1) according to any one of claims 1 to 9,

the measuring system (1) is applied to the tissue with its side having the housing opening (2a, 2b),

-controlling the radiation source (3) such that it emits radiation,

-the portion of the radiation source (3) is measured by the reference sensor (5) and the radiation detector (4),

-and normalizing the measurement values detected by the radiation detector (4) by means of the measurement values detected by the reference sensor (6).