U.S. patent application number 17/131032 was filed with the patent office on 2021-04-15 for apparatus and method for analyzing a material.
The applicant listed for this patent is DiaMonTech AG. Invention is credited to Alexander Bauer, Otto Hertzberg, Thorsten Lubinski.
Application Number | 20210109019 17/131032 |
Document ID | / |
Family ID | 1000005303511 |
Filed Date | 2021-04-15 |
United States Patent
Application |
20210109019 |
Kind Code |
A1 |
Bauer; Alexander ; et
al. |
April 15, 2021 |
Apparatus and Method for Analyzing a Material
Abstract
The invention relates, inter alia, to an apparatus for analyzing
a material, including an excitation emission device for generating
at least one electromagnetic excitation beam, in particular an
exciting light beam, having at least one excitation wavelength,
further including a detection device for detecting a reaction
signal, and a device for analyzing the material on the basis of the
detected reaction signal.
Inventors: |
Bauer; Alexander;
(Oberursel, DE) ; Hertzberg; Otto; (Frankfurt am
Main, DE) ; Lubinski; Thorsten; (Berlin, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
DiaMonTech AG |
Berlin |
|
DE |
|
|
Family ID: |
1000005303511 |
Appl. No.: |
17/131032 |
Filed: |
December 22, 2020 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
15781176 |
Jun 4, 2018 |
10876965 |
|
|
PCT/DE2015/200532 |
Dec 9, 2015 |
|
|
|
17131032 |
|
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/1455 20130101;
G01N 33/49 20130101; G01N 2201/06113 20130101; A61B 5/1495
20130101; G01N 2021/1712 20130101; A61B 2560/0238 20130101; A61B
5/14532 20130101; G01N 21/552 20130101; A61B 5/0004 20130101; A61B
5/4839 20130101; A61B 5/1451 20130101; G01N 21/171 20130101; G01N
21/1717 20130101; G01N 2021/1725 20130101; G01N 21/636
20130101 |
International
Class: |
G01N 21/552 20060101
G01N021/552; A61B 5/1455 20060101 A61B005/1455; A61B 5/00 20060101
A61B005/00; G01N 21/17 20060101 G01N021/17; G01N 21/63 20060101
G01N021/63 |
Claims
1. An analysis device for analyzing a material having an excitation
transmission device for generating at least one excitation light
beam with at least one excitation wavelength, and radiating the at
least one electromagnetic excitation beam into a material volume,
which is located underneath a first region of the surface of the
material, an optical medium, which in operation is in contact with
said first region of the surface of the material, a detection
device for detecting a response signal, and a device for analyzing
the material on the basis of the detected response signal.
2. The analysis device according to claim 1, wherein the device
comprises a system for emitting a measurement beam, which is
arranged so that the emitted measurement beam penetrates the
optical medium and is reflected at an interface of the optical
medium and the surface of the material, and the detection device is
a device for receiving the reflected measuring beam which forms the
response signal and for directly or indirectly detecting a
deflection of the reflected measuring beam.
3. The analysis device according to claim 1, wherein in order to
detect a response signal, the detection device is configured to
detect a parameter change of the optical medium in a region
adjacent to the first region, as a result of the response signal,
wherein said parameter change is one or both of a deformation and a
density change of the optical medium.
4. The analysis device according to claim 3, wherein the detection
device comprises one of a piezo-element, which is connected to the
optical medium or integrated therein, as a detector for detecting
said deformation or density change and temperature sensors as
detectors for detecting the response signal.
5. The analysis device according to claim 1, wherein the device
comprises a device for the intensity modulation of the excitation
light beam, and the detection device is suitable for detecting a
time-dependent response signal as a function of one or both of the
wavelength of the excitation light and the intensity modulation of
the excitation light.
6. The analysis device according to claim 1, wherein the excitation
transmission device comprises two or more transmission elements in
the form of a one-, two- or multi-dimensional transmission element
array, wherein the two or more transmission elements each generate
their own electromagnetic excitation beam and radiate the same into
the volume below the first region and the wavelengths of the
electromagnetic excitation beams of the two or more transmission
elements are different.
7. The analysis device according to claim 1, wherein the excitation
transmission device is directly, or indirectly by means of an
adjustment device, mechanically fixedly connected to said optical
medium.
8. The analysis device according to claim 5, wherein the device for
the intensity modulation comprises or is formed by an electrical
modulation device, which is electrically connected to the
excitation transmission device and electrically controls it.
9. The analysis device according claim 5, wherein the device for
intensity modulation comprises one of a controlled mirror arranged
in the beam path and a layer which is arranged in the beam path and
is controllable with respect to its transparency, or is formed by
such a layer.
10. The analysis device according to claim 1, wherein one or more
of a device for emitting a measuring beam, the detection device and
the excitation transmission device is/are directly mechanically
fixedly connected to the optical medium or coupled to the same by
means of a fiber-optic cable.
11. The analysis device according to claim 1, wherein the optical
medium directly supports an imaging optics, or an imaging optics is
integrated into the optical medium.
12. The analysis device according to claim 1, wherein the surface
of the optical medium has a plurality of partial faces inclined
towards each other, at which the measuring beam is reflected
multiple times.
13. The analysis device according to claim 1, wherein one or more
reflective surfaces are provided in or on the optical medium for
reflecting the measuring beam.
14. The analysis device according to claim 1, wherein one or more
of the excitation transmission device, a device for the emission of
a measuring beam and the detection device are directly attached to
each other or to a common support.
15. The analysis device according to claim 1, wherein the
excitation transmission device has an integrated semiconductor
component, which comprises one or more laser elements and at least
one micro-optical component and an additional modulation
element.
16. The analysis device according to claim 1, wherein the analysis
device has a wearable housing which can be fastened to the body of
a person, wherein the excitation transmission device and the
detection device are arranged and configured in such a way that the
material to be analyzed is measured on the side of the housing
facing away from the body.
17. The analysis device according to claim 16, wherein the housing
of the device has a window which is transparent for the excitation
light beam on its side facing away from the body in the intended
wearing position.
18. The analysis device according to claim 16, wherein the
excitation transmission device has an integrated semiconductor
component, which comprises a plurality of laser elements and a
modulation element for modulating the intensity of excitation light
beams generated by corresponding ones of said plurality of laser
elements, wherein said modulation element is one of a mirror, which
is movable relative to the rest of the semiconductor device and is
controllable with respect to its position, a layer with
controllable radiation permeability, and an electronic control
circuit for the modulation of the plurality of laser elements.
19. The analysis device according to claim 16, wherein the
excitation transmission device is directly, or indirectly by means
of an adjustment device, mechanically fixedly connected to said
optical medium.
20. The analysis device according to claim 16, wherein one or more
of the excitation transmission device, the device for the emission
of the measuring beam and the detection device are directly
attached to each other or to a common support.
21. The analysis device according to claim 16, wherein one or more
of a device for emitting a measuring beam, the detection device and
the excitation transmission device is/are directly mechanically
fixedly connected to the optical medium or coupled to the same by
means of a fiber-optic cable.
22. A method for analyzing a material, wherein in the method an
optical medium is brought into contact with a surface of the
material, with an excitation transmission device, at least one
electromagnetic excitation light beam with at least one excitation
wavelength is generated by an at least partially simultaneous or
consecutive operation of a plurality of laser emitters of a laser
light source, and the at least one excitation light beam is
radiated into a material volume, which is located underneath a
first region of the surface of the material, with a detection
device a response signal is detected and the material is analyzed
on the basis of the detected response signal.
23. The method according to claim 22, wherein using different
modulation frequencies of the excitation transmission device,
response signals, in particular temporal response signal waveforms
or patterns, are successively determined and wherein a plurality of
response signal waveforms or patterns at different modulation
frequencies are combined with each other and that, in particular,
specific information for a depth range under the surface is
obtained from this.
24. The method according to claim 23, wherein response signal
waveforms or patterns at different modulation frequencies are
determined for different wavelengths of the excitation beam and
from this, in particular specific information is obtained for each
depth range under the surface.
25. The method according to claim 24, wherein when a plurality of
modulation frequencies of the excitation light beam are used at the
same time, the detected signal is resolved into its frequencies by
means of an analytical procedure, and only the partial signal that
corresponds to the desired frequency is filtered out.
26. The method according to claim 22, wherein the emitted
excitation light beam is radiated in such a way that it penetrates
the optical medium and exits the same at a predetermined point on
the surface of the optical medium, with a device for emitting a
measuring beam, a measuring beam is generated in such a way that it
penetrates the optical medium and is reflected at an interface of
the optical medium and the surface of the material, and a reflected
measuring beam forming the response signal is measured with the
detection device, and the deflection of the reflected beam is
directly or indirectly detected.
27. The method according to claim 22, wherein said material is
formed by a body part of a patient, and as a function of a material
concentration identified in the material, a dosing device is
activated for delivering a substance into the body of the patient,
an acoustic or visual signal is output or a signal is delivered to
a processing device via a wireless connection.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This Application is a continuation application of and claims
priority to U.S. patent application Ser. No. 15/781,176, filed Jun.
4, 2018, and issuing as U.S. Pat. No. 10,876,965 on Dec. 29, 2020,
which is a U.S. national stage entry under 35 U.S.C. .sctn. 371 of
Patent Cooperation Treaty Application PCT/DE2015/200532, filed Dec.
9, 2015. The foregoing applications are incorporated herein by
reference in their entirety.
TECHNICAL FIELD
[0002] The present intellectual property right relates to a device
and a method for analyzing a material. The device described here
and the procedure described here can be used for example for the
analysis of animal or human tissue, in one embodiment for the
measuring of glucose or blood sugar.
BACKGROUND
[0003] Known methods for analyzing a material, in particular for
the measurement of blood sugar are described in the following
publications, for example: [0004] Guo et al.: "Noninvasive glucose
detection in human skin using wavelength modulated differential
laser photothermal radiometry", Biomedical Optics Express, Vol, 3,
2012, No. 11, [0005] Uemura et al.: "Non-invasive blood glucose
measurement by Fourier transform infrared spectroscopic analysis
through the mucous membrane of the lip: application of a
chalcogenide optical fiber System", Front Med Biol Eng. 1999; 9(2):
137-153, [0006] Farahi et al.: "Pump probe photothermal
spectroscopy using quantum cascade lasers", J. Phys. D. Appl. Phys.
2012 and [0007] M. Fujinami et al.: "Highly sensitive detection of
molecules at the liquid/liquid interface using total internal
reflection-optical beam deflection based on photothermal
spectroscopy", Rev. Sei. Instrum., Vol. 74, Number 1 (2003). [0008]
(1) von Lilienfeld-Toal, H. Weidenmuller, M. Xhelaj , A. Mantele,
W. A Novel Approach to Non-Invasive Glucose Measurement by
Mid-Infrared Spectroscopy: The Combination of Quantum Cascade
Lasers (QCL) and Photoacoustic Detection Vibrational Spectroscopy,
38:209-215, 2005. [0009] (2) Pleitez, M. von Lilienfeld-Toal, H.
Mantele W. Infrared spectroscopic analysis of human interstitial
fluid in vitro and in vivo using FT-IR spectroscopy and pulsed
quantum cascade lasers (QCL): Establishing a new approach to
non-invasive glucose measurement Spectrochimica acta. Part A,
Molecular and biomolecular spectroscopy, 85:61-65, 2012 [0010] (3)
Pleitez, M. et al. In Vivo Noninvasive Monitoring of Glucose
Concentration in Human Epidermis by Mid-Infrared Pulsed
Photoacoustic Spectroscopy Analytical Chemistry, 85: 1013 -1020,
2013 [0011] (4) Pleitez, M. Lieblein, T. Bauer, A. Hertzberg, 0.
von Lilienfeld-Toal, H. Mantele, W. Windowless ultrasound
photoacoustic cell for in vivo mid-IR spectroscopy of human
epidermis: Low interference by changes of air pressure,
temperature, and humidity caused by skin contact opens the
possibility for a non-invasive monitoring of glucose in the
interstitial fluid Review of Scientific Instruments 84, 2013 [0012]
(5) M. A. Pleitez Rafael, 0. Hertzberg, A. Bauer, M. Seeger, T.
Lieblein, H. von Lilienfeld-Toal, and W. Mantele. Photo-thermal
deflectometry enhanced by total internal reflection enables
non-invasive glucose monitoring in human epidermis. The Analyst,
November 2014.
SUMMARY OF THE EMBODIMENTS
[0013] The object of the invention is to specify a device with
which a material, in particular an animal or human tissue or a
component or ingredient of the tissue, can be analyzed particularly
simply and cost-effectively.
[0014] This object is achieved by, inter alia, a device having the
features as defined in claim 1. Embodiments of the device are
specified in dependent claims.
[0015] Reference is made to the German patent DE 10 2014 108 424
B3, the content of which is referred to specifically, and the
content of which this application extends; by this explicit
reference made here, the full contents of German patent DE 10 2014
108 424 B3 is therefore also to be regarded as part of the
disclosure of this application ("incorporation by reference" for
all details of that disclosure). In particular, this reference
relates to all the features given in the patent claims as granted.
In addition, the reference relates in particular to details of the
excitation light beam mentioned there, for example, to the
numerical values of the pulse frequencies and wavelengths
(wavelength ranges) cited there, and also to the details relating
to the measurement of glucose content in the interstitial
fluid.
[0016] In addition to the subject matter of the claims and
exemplary embodiments which are directly and explicitly mentioned
at the time of filing, the present PCT property rights application
also relates to other aspects, which are listed at the end of the
present description. These aspects can be combined, either
individually or in groups, with features of the claims cited at the
time of filing. These aspects, whether taken alone or combined with
each other or with the subject matter of the claims, represent
stand-alone inventions. The applicant reserves the right to make
these inventions the subject matter of claims at a later date. This
can be done in the context of this application or else in the
context of subsequent divisional applications, continuation
applications (in the USA), continuation-in-part applications (in
the USA) or subsequent applications claiming the priority of this
application.
[0017] In the following, however, the subject matter of the claims
mentioned at the time of filing will be discussed first.
[0018] A device for analyzing a material is provided, with an
excitation transmission device for generating at least one
electromagnetic excitation beam, in particular an excitation light
beam with at least one excitation wavelength, a detection device
for detecting a response signal and a device for analyzing the
material on the basis of the detected response signal.
[0019] A major advantage of this device is the fact that it can be
used to analyze a material in a very simple and reliable way.
[0020] The term light is understood here to mean electromagnetic
waves or electromagnetic radiation in the visible range, in the
near and far infrared range and in the UV range.
[0021] In an exemplary embodiment of the device it is provided that
[0022] the excitation transmission device is a radiation source, in
one embodiment a monochromatic, in particular polarized radiation
source or light source, more particularly a laser light source,
[0023] the device has an optical medium, which is in direct contact
with the material, in particular with a first region of the surface
of the material, [0024] wherein the excitation transmission device
is preferably arranged in such a way that the emitted excitation
beam penetrates the optical medium and exits the same again at a
predetermined point on the surface of the optical medium, and
[0025] the device comprises a system for emitting a measuring beam,
in particular a measuring light beam, which is arranged in such a
way that the emitted measuring beam penetrates into the optical
medium and wherein in operation the measuring beam and the
excitation beam preferably overlap at an interface of the optical
medium and the surface of the material at which the measuring beam
is reflected, and [0026] the detection device is a device for
receiving the reflected measuring beam which forms the response
signal, and/or for directly or indirectly detecting a deflection of
the reflected measuring beam.
[0027] Preferably, the device has an optical medium which is in
direct contact with the material, in particular with a first region
of the surface of the material, in one embodiment the skin of a
human being, wherein for detecting a response signal the detection
device detects a parameter change of the optical medium, in
particular in a region adjacent to the first region, as a result of
the response signal, in particular a deformation and/or density
change of the optical medium as a result of a local, time-dependent
heating. The optical medium may consist of a material which is
optically transparent or transparent to infrared radiation or
ultraviolet radiation, in general to the excitation beam and the
measuring beam, such as glass, crystal, zinc sulphide (ZnS), zinc
selenide (ZnSe), germanium (Ge), silicon (Si) and diamond or a
transparent plastic, in one embodiment a polyethylene. A local
heating in response to a transport or transfer of heat from the
material to be analyzed or from a substance of the material into
the optical medium leads to a change therein, for example, a
material deformation or thermal stresses or local changes in
refractive index, which are detectable.
[0028] The material can in one embodiment be the tissue of a living
organism, in particular a human being, wherein the material surface
can be the skin. Substances in the tissue can then be analyzed or
measured.
[0029] It can also be provided that the detection device has a
piezo-element connected to the optical medium or integrated into
it, as a detector for detecting a stress, deformation and/or
density change.
[0030] It can also be provided that the detection device has at
least one temperature sensor as a detector for detecting the
response signal. This can be arranged directly on the optical
medium or in its surroundings, depending on the measuring
principle.
[0031] Preferably, the device has a system for intensity modulation
of the excitation light beam.
[0032] The detection device is preferably suitable for detecting a
time-dependent response signal as a function of the wavelength of
the excitation light and/or the intensity modulation of the
excitation light.
[0033] It can also be provided that the excitation transmission
device radiates at least one electromagnetic excitation beam into a
volume of material, which is underneath a first region of the
surface of the material.
[0034] Particularly preferably the excitation transmission device
comprises two or more transmission elements, in particular in the
form of a one-, two- or multi-dimensional transmission element
array. This can therefore be implemented as a surface array of
transmission elements, or else as a transmission element strip (in
one embodiment semiconductor laser arrays or QCL arrays, wherein
QCL stands for quantum cascade laser).
[0035] It can also be provided that the two or more transmission
elements each generate their own electromagnetic excitation beam
and radiate this into the volume underneath the first region. The
different excitation beams can also be emitted successively, or
else at least partially at the same time. The different
transmission elements can also be operated with different
modulation frequencies at the same time.
[0036] The wavelengths of the electromagnetic excitation beams of
the two or more transmission elements are preferably different. The
wavelengths are preferably chosen in such a way that a substance to
be detected in the material to be analysed absorbs radiation of
these wavelengths particularly well. Additionally or alternatively,
wavelengths or wavelength ranges can also be selected, which the
substance to be detected does not absorb, but which are absorbed by
other substances (so-called tolerant wavelengths), to distinguish
the substance to be analyzed from other substances.
[0037] In one embodiment the excitation transmission device
comprises two or more lasers, in particular in the form of a one-
or two-dimensional laser array, wherein a plurality of rows of
laser elements can be staggered and arranged offset one behind
another in order to save space, in one embodiment in the form of a
laser strip and/or two or more light-emitting diodes, in particular
in the form of a one- or two-dimensional diode array, in a
depth-staggered manner and offset relative to one another, in one
embodiment of a two-dimensional array or a strip. The output beams
of the arrays can either have individual beam axes, close together
or in parallel, for each beam element, or can have a same beam
axis, by means of already integrated sets of optics.
[0038] Regarding the structure of the device, it can be provided
that the excitation transmission device is directly or
indirectly--preferably by means of an adjustment
device--mechanically fixedly connected to an optical medium, which
is in direct contact with the material, in particular with the
first region of the surface of the material. Therefore, the
excitation transmission device can be aligned and fixed relative to
the optical medium as early as the manufacturing stage, or at least
before deployment.
[0039] For the purpose of mounting and/or alignment or adjustment
of an excitation transmission device and/or elements of a detection
device, the optical medium can have at least one built-in elevation
and/or indentation, such as a bridge, a shoulder, a half-sphere
mounted thereon, a mounted block, a cone or a drilled hole, a
groove, a hollow or other recess, in or on which the
above-mentioned elements (the excitation transmission device and/or
elements of a detection device) can be placed, rested on or to
which they can be aligned or fixed. It is also possible that
aligned matching surfaces be formed on the optical medium by
machining or in a casting process
[0040] With regard to the device for intensity modulation it can be
provided that it comprises an electrical or electro-mechanical
modulation device, which is electrically connected to the
excitation transmission device and in particular, electrically
controls the same, or is formed by such a device. The modulation
device can generate an intensity modulation of the excitation beam,
in one embodiment a periodic intensity modulation, also for example
in the form of rectangular pulses, a sawtooth function or a
sine-wave function or other periodic function.
[0041] Alternatively or additionally, the device for intensity
modulation can comprise at least one controlled mirror arranged in
the beam path, by the control of which the intensity of the
excitation beam can be modulated by deflection.
[0042] Alternatively or additionally, the device for intensity
modulation can comprise at least one layer, which is arranged in
the beam path and is controllable with respect to its transparency,
or can be formed by such a layer. Therefore, the modulation element
can be designed in the form of a transmission element which is
controlled with respect to its transmission. The modulation element
can generate a plurality of spatially separated light beams from
one light beam. It can also be provided in one embodiment that the
surface of a sample can be scanned with the modulation element. In
one embodiment, the modulation element can be controlled together
with the array of light sources/laser sources.
[0043] A device for emitting a measuring beam, in particular a
measuring light beam, is in one embodiment provided for emitting
the measuring beam into the particular area of an optical medium,
which is in contact with the first region of the surface of the
material.
[0044] The device for emitting a measuring beam and the detection
device are aligned to each other in one embodiment in such a way
that the detection device detects the measuring beam as the
time-dependent response signal, after this beam has been reflected
at least once at the interface of the optical medium that is in
contact with the material, in particular with the first region of
the surface of the material.
[0045] With a view to ease of assembly, it is advantageous if the
device for emitting a measuring beam and/or the detection device
and/or the excitation transmission device are directly fixedly
mechanically connected to the optical medium and/or are coupled to
the same by means of one or more fiber-optic cables.
[0046] Embodiments are also possible, in which the optical medium
directly supports an imaging optics and/or an imaging optics is
integrated into the optical medium.
[0047] In addition, embodiments are conceivable in which the
surface of the optical medium has a plurality of partial faces
inclined towards each other, at which the measuring beam, in
particular the measuring light beam, is reflected multiple
times.
[0048] Embodiments can also be provided, in which one or more
mirror surfaces for reflection of the measuring beam, in particular
the measuring light beam, are provided in or on the optical
medium.
[0049] With a view to a compact design, it is conceivable that the
excitation transmission device and/or the device for emitting the
measuring beam and/or the detection device are directly attached to
each other or to a common support. In one embodiment, the various
devices can be fixed to the support by welding or gluing or by
screws or a snap-in connection, wherein an adjustment facility can
be provided, either during assembly or else at a later time, by
means of an adjusting screw or other mechanical adjustment device.
In particular, the device for emitting the measuring beam and/or
the detection device should be, or capable of being, easily aligned
with respect to each other. Therefore, it can be useful to attach
these two devices directly to the optical medium. The device for
emitting the measuring beam and/or the detection device, given
suitable guidance of the measuring beam, can also be arranged next
to each other on the same side of the optical medium and on a
common support, in one embodiment attached to a common printed
circuit board or a common semiconductor, or else implemented as a
common integrated semiconductor device, in one embodiment as a
common integrated semiconductor component. This support can then be
adjusted as a unit relative to the optical medium, in a particular
embodiment, even without further changing the relative position
between the device for transmitting the measuring beam and/or the
detection device.
[0050] The support is preferably formed by a printed circuit board,
a metal plate or plastic plate or a housing or part of a housing of
the device.
[0051] It can also be provided that the excitation transmission
device comprises an integrated semiconductor device, which has one
or more laser elements and at least one micro-optical component and
preferably an additional modulation element. The above-mentioned
elements can be manufactured, in one embodiment etched, jointly
from one semiconductor blank or at least accommodated in a common
housing.
[0052] It can also be provided that the modulation element has at
least one element, in particular a mirror, which is movable
relative to the rest of the semiconductor device and is
controllable with respect to its position. This can be controlled
by means of a MEMS device.
[0053] It can also be provided that the modulation element has a
layer which is controllable in terms of its radiation
permeability.
[0054] It can also be provided that the modulation element has an
electronic control circuit for the modulation of the one or more
laser elements. In one embodiment the modulation element can be
constructed in such way that it varies the excitation beam in a
time-dependent manner by interference, phase offset/path offset or
a polarizing filter device or other known modulation
mechanisms.
[0055] The micro-optical component or components can be mirrors or
lenses that are either integrated into the semiconductor component
or made from it in a subtractive process, in particular by
etching.
[0056] The described device for analyzing a material can determine
a measurement value of a material concentration, in one embodiment
a glucose concentration. The device can have an interface to a
device for displaying measurement values and their analysis, for
example by means of a color code for a user of the device, and/or
to a dosing device for a substance which can be dispensed into the
material, in particular the tissue or, more generally, the body of
an organism. The device can also directly comprise such a dosing
device. In this case, the device can also have a system for
detecting or analyzing the material surface, in one embodiment the
skin surface or in another embodiment the ocular surface or iris of
a living being, which enables the identification of a person or a
living being based on a comparison with reference data and can
therefore be used to ensure that appropriate reference values
and/or calibration values are provided for the analysis of the
material and the control of the dosing device. Determined
characteristic values of the material surface, in one embodiment a
fingerprint or the structure of an iris of the eye, can, in
addition to identifying and authenticating a person, e.g. against a
database, also be used for encrypting the communication of status
values and controlling the dosing device which, encrypted or
unencrypted, can in principle be originated from the database. In
one embodiment the dosing device can be equipped with a sensor to
determine a fill level of a substance to be dispensed, such as in
one embodiment insulin and/or glucagon, and can have a device for
transmitting the fill level to the device for material analysis
and/or directly to the database.
[0057] In addition, the device can have an interface, in one
embodiment a radio interface to the database, to which the
measurement values can be sent and which can process the data. The
database can be created in such a way that it processes and stores
the data from a plurality of patients, that is, in one embodiment
also the data from a plurality of similar devices for analyzing a
material, and in one embodiment it also controls individual dosing
devices for dispensing substances. The database can also further
process the measured data relating to the analyzed material and
determine derived analysis results, such as any trend in the
values, first and second time derivatives, minima, maxima, standard
deviations of material quantities or concentrations, blood sugar
values or other physiological values of patients, compare them and
derive signals from them, which in one embodiment also includes
alarm signals. The fill level of the dosing device can also be
detected and processed by the database in order to determine, in
one embodiment, a temporal extent of the fill level or the need for
refilling and to signal this directly to the patient's device or to
a service facility. For this purpose, the database can be connected
to a communication device in a service facility, in one embodiment
in a hospital or a medical practice. For the purpose of sending
data from and/or to a database, the device can in one embodiment be
connected to a mobile device or a pager by means of a radio link,
in one embodiment Bluetooth or WLAN or Wifi, or other transmission
methods. The device can also be directly equipped with a WLAN
interface and an internet client.
[0058] The subject matter also relates to a method for analyzing a
material, wherein in the method at least one electromagnetic
excitation beam with at least one excitation wavelength is
generated with an excitation transmission device by the successive
operation or the at least partially simultaneous operation of a
plurality of laser emitters of a laser light source, and a response
signal is detected with a detection device and the material is
analyzed on the basis of the detected response signal. In the
method, the thermal diffusivity in the material and the temporal
evolution or waveform of the response signal can be used to
characterize the nature of the material or a spatial distribution
of a substance in the material or to characterize the depth at
which the excitation beam is absorbed.
[0059] In one embodiment it can be provided that using different
modulation frequencies of the excitation transmission device,
response signals, in particular temporal response signal waveforms
or patterns, can be successively determined and that a plurality of
response signal waveforms or patterns at different modulation
frequencies can be combined with each other and that, in
particular, specific information for a depth range under the
surface is obtained from this.
[0060] It can also be provided that response signal waveforms or
patterns are determined at different modulation frequencies for
different wavelengths of the excitation beam and from these, in
particular specific information is obtained for each depth range
under the surface. When using a plurality of modulation frequencies
of the pump beam at the same time, it is possible, for example, to
resolve the detected signal into its frequencies using an
appropriate analysis method, for example a Fourier transformation;
the FT would only filter out the signal that corresponds to the
desired frequency.
[0061] It can also be provided that an optical medium is brought
into direct contact with the material, in particular with a first
region of the surface of the material, the emitted excitation beam
is generated and, in particular, emitted with the excitation
transmission device in such a way that it penetrates into the
optical medium and exits it again at a predetermined point on the
surface of the optical medium, that a measuring beam, in particular
a measuring light beam, is generated with a device for emitting a
measuring beam in such a way that this beam penetrates the optical
medium and that in particular, in operation, the measuring beam and
the excitation beam overlap at an interface of the optical medium
and the surface of the material at which the measuring beam is
reflected, and that a reflected measuring beam which forms the
response signal is measured and/or the deflection of the reflected
beam is directly or indirectly detected with the detection
device.
[0062] One aspect of the method is the focusing of the measurement
of the response signal on selected depth ranges underneath the
(distance intervals from the) material surface. The thermal
wavelength d has the greatest influence on the depth range measured
with the method. It is defined as d= (D/(.pi.*f)), where D is the
thermal diffusivity of the sample (here for example, skin) and f is
the modulation frequency of the excitation beam. Literature on the
thermal diffusivity of skin: [0063] U. Werner, K. Giese, B.
Sennhenn, K. Piamann, and K. Kolmel, "Measurement of the thermal
diffusivity of human epidermis by studying thermal wave
propagation," Phys. Med. Biol. 37(1), 21-35 (1992). [0064] A. M.
Stoll, Heat Transfer in Biotechnology, Vol 4 of Advances in Heat
Transfer, J. P. Hartnett and T. Irvin, eds. (New York, Academic,
1967), p 117.
[0065] In one embodiment, to eliminate response signals from the
topmost layers of the material, changes in the measurements
compared to previous measurements can be used, in case the
measurements in the top layers change more or less slowly in
comparison to other, deeper layers.
[0066] This can be the case in an embodiment in measurements on
human skin, where the topmost layers of the skin undergo virtually
no exchange with the lower layers and therefore physiological
parameters change very little. The time derivative of measurements
can also be applied to provide response signals to exclude the
signals from the topmost layers of the skin. Thus the measurement,
or at least the evaluation, can be limited to or focused on the
interstitial fluid in the skin.
[0067] It can also be provided that depending on a material
concentration identified in the material, a dosing device for
dispensing a substance, in particular into a patient's body, is
controlled and/or an acoustic and/or visual signal is output and/or
a signal is output to a processing device via a wireless
connection. In this case, in addition to a currently determined
measurement a temporal development or evolution of the measurement
values, a derivative of the measurement value, average values of
the measurements, maxima, minima, a standard deviation and
predefined thresholds for measurement values can be taken into
account and combined with the current measurement value. In one
embodiment, the processing device can be a database or connected to
a database, which collects and processes data from a plurality of
patients. The database can be either directly connected to a
control system of the device or be remote from and connected to it
via a communication interface.
[0068] To obtain increased security when operating a dosing device,
in particular for insulin, it can be provided that this is operated
locally or from a database under the control of a preset standard
procedure with preselected quantity deliveries at times that are or
can be specified, and that by means of the above-described device
meaningful deviations from preset delivery values can be determined
that are used for the correction and improvement of the control of
the dosing device. In this way, even in the event of a failure of
the device at least a normal or emergency operation of the dosing
device is guaranteed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0069] FIGS. 1 to 13 schematically show different elements of the
device and its elements, in some cases in different embodiments.
Specifically,
[0070] FIG. 1 shows a device in accordance with an embodiment of
the invention;
[0071] FIG. 2 shows an excitation transmission device in accordance
with an embodiment of the invention;
[0072] FIG. 3 shows a device in accordance with an embodiment of
the invention;
[0073] FIG. 4 shows a device in accordance with an embodiment of
the invention;
[0074] FIG. 5 shows a connector body in accordance with an
embodiment of the invention;
[0075] FIG. 6 shows a device in accordance with an embodiment of
the invention;
[0076] FIG. 7 shows a device in accordance with an embodiment of
the invention;
[0077] FIG. 8 shows a device in accordance with an embodiment of
the invention;
[0078] FIG. 9 shows a modulation device in accordance with an
embodiment of the invention;
[0079] FIG. 10 shows an excitation light source in accordance with
an embodiment of the invention;
[0080] FIG. 11 shows an excitation light source in accordance with
an embodiment of the invention;
[0081] FIG. 12 shows a device in accordance with an embodiment of
the invention; and
[0082] FIG. 13 shows a graph of a wavelength range blocked by a
filter in accordance with an embodiment of the invention.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
[0083] FIG. 1 shows an exemplary embodiment of a device 10 for
analyzing a material 101. The material 101 is preferably placed
directly on an optical medium 108, which can be designed as an
optically transparent crystal or glass body. The device for
analyzing the material 101 is used for example to measure the
glucose or blood sugar content in a fluid, such as in one
embodiment blood, and for producing a glucose or blood sugar level
indication BZA.
[0084] The device comprises an excitation transmission device 100
for emitting one or more electromagnetic excitation beams SA,
preferably in the form of excitation light beams with one or more
excitation wavelengths, into a volume 103 which is located in the
material 101 below a first region 102 of the surface of the
material. The excitation transmission device 100 is also referred
to in the following as "excitation light source" 100 for brevity.
The excitation light source 100 can be a laser which is tunable
with respect to its wavelength, in particular a tunable quantum
cascade lasers; it is preferable, as will be explained below, to
use a light source strip or a light source array with at least two
single emitters, in particular semiconductor lasers, each of which
emits a specified individual wavelength.
[0085] In addition, a device 104 for the intensity modulation of
the excitation light beam or beams SA is provided, which is
preferably formed by a modulation device for the excitation light
source, in particular for controlling it, and/or by at least one
controlled mirror arranged in the beam path and/or by a layer,
which is arranged in the beam path and is controllable with respect
to its transparency.
[0086] In addition, the device has a system 105 for emitting an
electromagnetic measuring beam 112, in particular a measuring light
beam, which is reflected, preferably totally reflected, at the
interface GF between the material 101 and the optical medium
108.
[0087] A detection device 106 is used for the detection of the
reflected measuring beam 112, which forms a time-dependent response
signal SR; the amplitude of the response signal SR is influenced by
the wavelength of the excitation light SA and the intensity
modulation of the excitation light SA, as will be explained in more
detail below by means of examples.
[0088] The amplitude of the measuring signal depends on the
wavelength of the excitation beam, the absorption properties of the
sample and the thermal properties, in particular the thermal
diffusivity and thermal conductivity of the sample and of the
optical element. In addition, the coupling of the thermal signal
from the sample into the optical element also plays a role.
[0089] A device 107 for analyzing the material evaluates the
detected response signals SR and in one embodiment generates a
glucose or blood sugar level indication BZA.
[0090] Hereafter, the operation of the device 10 in accordance with
FIG. 1 and in this connection, an example of a method for analyzing
a material 101 will be described in more detail for the case in
which the material 101 to be analyzed is human or animal tissue,
and as part of the analysis of the material a glucose or blood
sugar level indication BZA is to be determined.
[0091] With the device 105 an electromagnetic measurement beam 112,
which is preferably a light beam in the visible wavelength range or
an infrared light beam, is irradiated into the optical medium 108;
this measurement beam 112 impinges on the interface GF below the
first region 102 of the surface of the tissue. At the interface GF
the measuring beam 112 is reflected and reaches the detection
device 106, which measures the reflected measurement beam 112.
[0092] At the same time, one or more excitation beams SA, which are
preferably infrared beams, are generated with the excitation light
source 100. The wavelength of the infrared beams is preferably in a
range between 3 .mu.m and 20 .mu.m, particularly preferably in a
range between 8 .mu.m and 11 .mu.m.
[0093] The excitation beams SA are intensity- or
amplitude-modulated with the device 104 for intensity modulation.
In one embodiment short light pulses are generated with the device
104 for intensity modulation, preferably with a pulse frequency of
between 1 kHz and 1 MHz, or else pulse packets (double or multiple
modulation), preferably with envelope frequencies of 1-10 kHz.
[0094] The modulated excitation beams SA are coupled into the
optical medium 108 and after passing through the interface GF
arrive in the volume 103 within the tissue.
[0095] The wavelength of the excitation beams SA--with a view to
the example of blood glucose measurement explained here--is
preferably chosen such that the excitation beams SA are
significantly absorbed by glucose or blood sugar. For measuring
glucose or blood sugar the following infrared wavelengths are
particularly well suited (vacuum wavelengths): 8.1 .mu.m, 8.3
.mu.m, 8.5 .mu.m, 8.8 .mu.m, 9.2 .mu.m, 9.4 .mu.m and 9.7 .mu.m. In
addition, glucose-tolerant wavelengths can be used, which are not
absorbed by glucose, in order to identify other substances present
and allow for excluding their effect on the measurement.
[0096] Due to the absorption of the excitation beams SA in the
tissue in the region of the volume 103, a local temperature
increase is induced, which triggers a heat transfer and thereby
pressure waves in the direction of the interface GF; due to the
resulting temperature and pressure fluctuations at the interface
GF, the refractive index and/or the deformation, microstructure and
the reflection behavior are modulated in the region 102 and/or in
the reflection region of the interface GF, and the beam path of the
measuring beams 112 is affected.
[0097] If it is assumed, for example, that without excitation beams
SA the alignment between the system 105 and the detection device
106 is optimal and a maximum received power is detected by the
detection device 106, then due to the absorption of the excitation
beams SA in the region of the volume 103 and due to the heat
transport and the pressure waves, an (at least temporary) change in
the amplitude or, in the case of a periodic modulation, the phase
of the reflected measuring beam 112 can be induced, or an intensity
modulation of the reflected measurement beam 112 can occur. The
extent of the intensity modulation depends on the wavelength of the
excitation beams SA (because of the necessary absorption in the
tissue) and on the pulse frequency of the excitation beams SA (due
to the temperature transport and the pressure waves from the tissue
interior in the direction of the interface GF) and on the thermal
properties of the sample and the medium.
[0098] The change in the reflection of the measuring beam 112
and/or the time-dependent change in the response signal SR is
quantitatively acquired by the detection device 106, and the
detection result D reaches the device 107.
[0099] On the basis of previously carried out calibration or
comparison measurements, which in one embodiment are stored in a
memory 107a of the device 107 in the form of comparison tables or
comparison curves, the current concentration of glucose or blood
sugar within the tissue or within the volume 103 can be deduced and
a corresponding glucose or blood sugar indication BZA can be
produced. The comparison tables or comparison curves may have been
created, for example on the basis of glucose or blood sugar levels
which were determined based on blood samples.
[0100] Particularly preferred embodiments and variants of devices
10 for analyzing a material 101 are described below with reference
to FIGS. 2 to 10.
[0101] The excitation transmission device 100 for emitting the
excitation light beam or beams can be designed as an array, as
shown in FIG. 2. The array has at least 5, advantageously at least
10, more advantageously at least 15 or at least 50 or 100
individually controllable emitters 100a for monochromatic light in
the absorption spectrum of a material to be analyzed.
[0102] The array preferably generates beams with monochromatic
light with one or more, particularly preferably all of the
following wavelengths (vacuum wavelengths): 8.1 .mu.m, 8.3 .mu.m,
8.5 .mu.m, 8.8 .mu.m, 9.2 .mu.m, 9.4 .mu.m and 9.7 .mu.m and if
desired, in addition glucose-tolerant wavelengths.
[0103] The device 105 for emission of the measuring light beam 112
and the detection device 106 can be arranged separately from the
optical medium 108, as shown in FIG. 1. With a view to a minimal
space requirement and minimal installation effort, it is regarded
as advantageous if the device 105 for the emission of the measuring
light beam 112 and the detection device 106 108 are mounted
directly on the optical medium, preferably on opposite surface
sections 108a and 108b of the optical medium 108, as FIG. 3
shows.
[0104] It can be provided that the excitation device/excitation
light source 100 is permanently mechanically connected to the
optical medium 108 either directly or by means of an adjustment
device 109. The adjustment device 109 preferably allows an
adjustment of the distance of the excitation light source 100 from
the optical medium 108, and/or an adjustment in the beam
longitudinal direction and/or an adjustment in a plane
perpendicular thereto (see FIG. 4).
[0105] As shown in FIGS. 3, 4, 6, 7 and 8, the device 105 can be
provided for emission of the measuring light beam 112 into the
region of the optical medium 108 that is in contact with the first
region 102 of the material surface. Such an arrangement allows the
measuring light beam 112 to be irradiated at a flat angle and a
total internal reflection to be induced at the interface of the
optical medium 108 with the material 101.
[0106] By injecting the radiation at a flat (small) angle (to the
sample surface), the mirage deflection, analogously to the known
photothermal `Bouncing Method`, can be made more effective and at
the same time the deformation-induced deflection of the measuring
beam can be reduced. The angle between the sample surface and the
measuring beam in one embodiment can be selected to be less than 20
degrees, less than 10 degrees, in particular less than 5 degrees,
more particularly less than 2 degrees or 1 degree, in order to
exploit this effect.
[0107] Conversely, by providing the irradiation at steeper (larger)
angles (to the material surface), by analogy to the known
photothermal `Bouncing Method` the deflection can be made more
effective and at the same time the mirage-effect related deflection
of the measuring beam can be reduced. The angle between the
material surface and the measuring beam in one embodiment can be
selected to be greater than 20 degrees, greater than 30 degrees, in
particular greater than 45 degrees, more particularly greater than
60 degrees or 70 degrees, to exploit this effect.
[0108] See related literature: [0109] M. Bertolotti, G. L. Liakhou,
R. Li Voti, S. Paolino, and C. Sibilia. Analysis of the
photothermal deflection technique in the surface refection theme:
Theory and Experiment. Journal of Applied Physics 83, 966
(1998)
[0110] The device 105 for emitting the measuring light beam 112
and/or the detection device 106 for detecting the measuring light
beam 112 and/or the response signal SR, can be mechanically
connected to the optical medium 108 in a supportive manner either
directly or by means of an adjustment device, and/or coupled
thereto by means of one or more fiber-optic cables 120.
[0111] It can also be provided, as shown in FIG. 6, that the
optical medium 108 directly supports an imaging optics 128 and/or
an imaging optics 129 (in each case) in the form of a lens or other
reflection or refraction means, and/or that an imaging optics is
integrated into the optical medium 108. The imaging optics can,
however also be integrated into the excitation transmission device
or the device for generating the measuring beam, for example, in
the form of a lens or other reflection or diffraction element, if
these are designed as integrated components and/or as a
semiconductor component. The imaging optics can in one embodiment
be subtractively formed from the same semiconductor element by
etching as the respective integrated circuit, which has a radiation
source for the excitation or measuring beam.
[0112] It can also be provided, as shown in FIG. 7, that the
surface of the optical medium 108 has a plurality of partial faces
110, 111 inclined towards each other, at which the measuring light
beam 112, is reflected or refracted multiple times.
[0113] It can also be provided, as shown in FIG. 3, that in or on
the optical medium 108 one or more mirror surfaces 113, 114 are
provided for reflecting the measuring light beam 112 (and therefore
the response signal SR.) These mirror surfaces can be formed by
inhomogeneities within the optical medium 108 or by its outer
surfaces or by means of, for example, metallic or metallic coated
mirror elements that are integrated/fitted/cast-in or mounted on
the optical medium. This extends the optical path of the measuring
light beam 112 in the optical medium 108 until its entry into the
detection device 106, so that in the case of reflection at the
region of the surface of the medium 108, which is in contact with
the first region 102 of the material surface, a response
signal-dependent deflection of the measuring light beam 112 within
the optical medium 108 is increased. The deflection can then be
detected in the detection device 106 as an absolute deflection.
[0114] The detection device 106 can have a plurality of optically
sensitive surfaces, such as optically sensitive semiconductor
diodes, or else a plurality of staggered openings 116, 117, 118 in
a connector body 119 (FIG. 5), at which individual fiber-optic
cables 120 end (FIG. 4), into which the light of the measuring
light beam 112 is coupled depending on its deflection. The
fiber-optic cables 120 are then connected to a connector body 119,
which can be fixed to the optical medium 108, and direct the light
to the part of the detection device 106 arranged at the end of the
fiber-optic cable 120 (FIG. 4). The connector body 119 is then, in
the same way as the fiber-optic cable 120, also part of the
detection device 106 for detecting the measuring light beam.
[0115] For the sake of completeness, it should be noted that the
excitation transmission device can also send the excitation to the
material surface either as a whole or section by section by means
of one or more fiber-optic cables, and in one embodiment the
excitation transmission device can be directly coupled to one or
more fiber-optic cables, which are coupled to the optical
medium.
[0116] It can also be provided, as shown in FIG. 8, that the
excitation transmission device 100, the device 105 for emitting the
measuring light beam 112, and the detection device 106 are directly
attached to each other or to a common support 121. The support can
be formed by a plastic part, a printed circuit board or a metal
sheet, which is mounted in a housing 122. The support, which in
FIG. 8 is formed with a U-shaped cross section, can then at least
partially surround the optical medium 108 in one embodiment. The
optical medium can be attached to the support and adjusted relative
to it.
[0117] The support can also be formed by the housing 122 itself or
a housing part.
[0118] It can also be provided that the device with the housing 122
can be fastened to the body 123 of a person, wherein the excitation
transmission device 100 for emitting one or more excitation light
beams SA, the device 105 for emitting the measuring light beam 112
and the detection device 106 for detecting the time-dependent
response signal SR are arranged and configured in such a way that
the side that is suitable for performing the measurement (with a
measuring window transparent to the excitation radiation) of the
device is located on the side of the device facing away from the
body, so that the material to be analyzed can be measured on the
side 124 of the housing 122 facing away from the body 123. In
relation to this, FIG. 8 shows that the housing 122 is attached to
the body 123 of a person by means of a belt 125 belonging to the
housing 123, in one embodiment being in the form of a bracelet on a
wrist. On the opposite side 124 from the wrist, the housing then
has a window which is transparent to the excitation light beam SA,
or the optical medium 108 is fitted directly into the outwards
facing side 124 of the housing and itself forms the surface of some
sections of the housing.
[0119] As shown in FIG. 8, a fingertip 126 shown schematically by a
dashed line can then be placed on the optical medium 108 and
measured.
[0120] The optical medium 108 can be attached within the housing
122, in the same way as the support 121, or else directly attached
to the housing 122. The optical medium 108 can also be directly
connected to the support 121, wherein an adjustment device 127
should be provided for the relative positioning of the support 121
with respect to the optical medium.
[0121] It is also conceivable to attach the excitation light source
100, the device 105 and the detection device 106, or even just one
or two of these elements, directly to the optical medium 108 and
the other element or elements to the support 121.
[0122] Through the optical window in the housing 122 and/or through
the optical medium 108, other parameters of the material surface or
the positioned fingertip 126 can be measured, such as in one
embodiment, a fingerprint. For this purpose, in the housing an
optical detector 130 in the form of a camera, for example, can be
fastened to the support 121, which records a digital image of the
material surface through the optical medium 108. This image is
processed within a processing unit 107, which can be directly
connected to the detection device and also to the excitation
transmission device, in the same way as the measurement information
by the detection device 106. The processing device can also perform
control tasks for the measurement. It can also be at least
partially separated and remote from the remaining parts of the
device and communicate with these by means of a wireless
connection.
[0123] The image data from the camera 130 can thus be further
processed inside the housing, or via a radio link even outside the
housing, and compared with a personal identity database to retrieve
calibration data of the identified person.
[0124] This type of calibration data can also be stored for remote
retrieval in a database, in one embodiment, a cloud. The
measurement data from the detection device 106 can also be further
processed both within and outside of the housing.
[0125] If data are processed outside the housing, then the
resulting data should preferably be sent back to the device within
the housing by radio to be displayed there.
[0126] In either case, a display can be provided on the housing
122, which advantageously can be read through the optical window,
and in one embodiment also to some extent through the optical
medium. The display can also project an optical indicator through
the optical window onto a display surface and can have a projection
device for this purpose. The display can be used in one embodiment
to display a measurement or analysis result, in particular a
glucose concentration. The information can be output in one
embodiment via a symbolic or color code. By means of the display or
a signaling device parallel thereto, in one embodiment a proposal
for an insulin dose can be presented, dependent on other patient
parameters (e.g. insulin correction factor), or a signal can be
transmitted automatically to a dosing device in the form of an
insulin pump.
[0127] The connection of the device to and from an external data
processing device 131 can be implemented using all common
standards, such as fiber-optic cables, cable, wireless (e.g.
Bluetooth, WiFi), or else ultrasound or infrared signals.
[0128] FIG. 9 shows a modulation device with a controller 132,
which activates the excitation transmission device in a modulated
manner. Both the controller 132 and the detection device 106 for
the measuring light beam are connected to the evaluation device
107.
[0129] FIG. 10 shows an excitation light source 100, in front of
which a mirror device driven by a MEMS (micro-electromechanical
system) 135 is arranged, with one or more micro-mirrors 133, 134,
such as those known from optical image projector technology, for
the occasional deflection of the excitation light beam in a
deflection direction 136.
[0130] FIG. 11 shows an excitation light source 100, in front of
which an optical layer 138 with a transmission that can be
controlled by means of a control device 137 is arranged in the
excitation light beam, in one embodiment with LCD cells.
[0131] The present property rights application (as already
mentioned), in addition to the subject matter of the claims and
exemplary embodiments described above, also relates to the
following aspects. These aspects can be combined individually or in
groups, in each case with features of the claims. Furthermore,
these aspects, whether taken alone or combined with each other or
with the subject matter of the claims, represent stand-alone
inventions. The applicant reserves the right to make these
inventions the subject matter of claims at a later date. This can
be done either in the context of this application or else in the
context of subsequent divisional applications or continuation
applications claiming the priority of this application.
[0132] 1) A method for analyzing a material in a body, comprising:
[0133] emitting an excitation light beam with one or a plurality of
specific excitation wavelengths through a first region of the
surface of the body, [0134] intensity modulating the excitation
light beam with one or a plurality of frequencies, in particular
consecutively, by means of a component which differs from a
mechanical chopper, in particular by an electronic activation of
the excitation light source, an adjustment device for a resonator
of an excitation laser used as the excitation light source, or a
movable mirror device, a controllable diffraction device, a shutter
or mirror device which is coupled to a motor, such as a stepper
motor, or to an MEMS, or a layer in the beam path that can be
controlled in terms of its transmission, [0135] by means of a
detector positioned outside the body, detecting a response signal
in a time-resolved manner, which response signal is attributable to
the effect of the wavelength-dependent absorption of the excitation
light beam in the body.
[0136] In one embodiment the modulation can be performed by
interference or by influencing the phase or polarization of the
radiation of the excitation transmission device, in particular if
it comprises a laser light device.
[0137] 2) The method according to aspect 1, characterized in that
the excitation light beam is generated by a plurality of emitters
or multi-emitters, in particular in the form of a laser array,
which emit light with different wavelengths either simultaneously
or sequentially, or in arbitrary pulse patterns.
[0138] 3) The method according to aspect 1 or 2, characterized in
that on the first region of the surface of the body an acoustic
response signal is detected by an acoustic sensor.
[0139] 4) The method according to any of the aspects 1 to 3,
characterized in that a response signal is detected on the first
region of the surface of the body by means of an infrared radiation
sensor, in particular a thermocouple, a bolometer or a
semiconductor detector, for example a quantum cascade detector.
[0140] 5) The method according to any of the aspects 1 to 4,
comprising the steps of: [0141] producing the contact of an optical
medium with a material surface, so that at least one region of the
surface of the optical medium is in contact with the first region
of the surface of the body; [0142] emitting an excitation light
beam with an excitation wavelength into a volume in the material
located underneath the first region of the surface, in particular
through the region of the surface of the optical medium which is in
contact with the first region of the material surface, [0143]
measuring the temperature in the first region of the surface of the
optical medium using an optical pyrometric method, [0144] analyzing
the material on the basis of the detected temperature increase as a
function of the wavelength of the excitation light beam.
[0145] 6) The method according to aspect 5, characterized by
emitting a measurement light beam through the optical medium (10)
onto the region of the surface (12) of the optical medium (10)
which is in direct contact with the material surface, in such a way
that the measurement light beam and the excitation light beam
overlap at the interface of the optical medium (10) and the
material surface, at which the measurement light beam is reflected;
[0146] directly or indirectly detecting a deflection of the
reflected measurement light beam as a function of the wavelength of
the excitation light beam; and [0147] analyzing the material on the
basis of the detected deflection of the measurement light beam as a
function of the wavelength of the excitation light beam.
[0148] 7) The method according to one of the aspects 5 or 6,
characterized in that the measuring beam is generated by the same
light source that generates the excitation light beam.
[0149] 8) The method according to any one of aspects 5, 6 or 7,
characterized in that after the deflection and before the detection
within the optical medium, the measuring beam is reflected one or
more times outside of the optical medium or partially inside and
partially outside of the optical medium.
[0150] 9) The method according to aspect 1 or any one of the other
preceding or following aspects, characterized in that the measuring
light beam is an intensity-modulated, in particular pulsed
excitation light beam in particular in the infrared spectral range,
wherein in particular the modulation rate is between 1 Hz and 10
kHz, preferably between 10 Hz and 3000 Hz.
[0151] 10) The method according to aspect 1 or any one of the other
preceding or following aspects, characterized in that the light of
the excitation light beam/beams is generated by an integrated
arrangement with a plurality of individual lasers, in particular a
laser array, simultaneously or successively or partially
simultaneously and partially successively.
[0152] 11) The method according to aspect 1 or any one of the other
preceding or following aspects, characterized in that from the
response signals obtained at different modulation frequencies of
the excitation light beam, an intensity distribution of the
response signals is determined as a function of the depth below the
surface in which the response signals are produced.
[0153] 12) The method according to aspect 1 or any one of the other
preceding or following aspects, characterized in that from the
phase position of the response signals in relation to a modulated
excitation light beam at one or different modulation frequencies of
the excitation light beam, an intensity distribution of the
response signals is determined as a function of the depth below the
surface in which the response signals are produced.
[0154] 13) The method according to aspect 11 or 12, characterized
in that in order to determine the intensity distribution of the
response signals as a function of the depth below the surface, the
measurement results at different modulation frequencies are
weighted and combined with each other.
[0155] 14) The method according to aspect 11, 12 or 13,
characterized in that from the intensity distribution obtained over
the depth below the surface of the body, a material density of a
material is determined, which absorbs the excitation light beam in
specific wavelength ranges in a specific depth or depth range.
[0156] 15) The method according to aspect 1 or any one of the other
preceding or following aspects, characterized in that immediately
before or after or during the detection of the response
signal/signals at least one biometric measurement is carried out on
the body in the first region of the surface or directly adjacent to
this, in particular a measurement of a fingerprint, and the body,
in particular a person, is identified and in that in particular,
reference values (calibration values) can be assigned to the
detection of the response signals.
[0157] 16) A device for analyzing a material, [0158] having a
device for emitting one or more excitation light beams, each with
one excitation wavelength, into a volume which is located in the
material below a first region of its surface, with a device for
modulating an excitation light beam, which device is formed by a
modulation device of the radiation source, in particular its
controller, an interference device, a phase- or
polarization-modulation device and/or at least one controlled
mirror arranged in the beam path, and/or a layer arranged in the
beam path which is controllable with respect to its transparency,
and having a detection device for detecting a time-dependent
response signal as a function of the wavelength of the excitation
light and the intensity modulation of the excitation light, and
with a device for analyzing the material on the basis of the
detected response signals.
[0159] 17) The device according to aspect 16, with a device for
determining response signals separately according to different
intensity modulation frequencies and/or with a device for
determining response signals as a function of the phase position of
the respective response signal relative to the phase of the
modulation of the excitation light beam, in particular as a
function of the modulation frequency of the excitation light
beam.
[0160] 18) The device for analyzing a material according to aspect
16 or 17, with an optical medium for establishing the contact of
the surface of the optical medium with a first region of the
material surface, and with [0161] a device for emitting an
excitation light beam with one or more excitation wavelengths into
a volume located in the material underneath the first region of the
surface, in particular through the region of the surface of the
optical medium which is in contact with the material surface, and
with a device for measuring the temperature in the region of the
surface of the optical medium which is in contact with the material
surface using an optical method, and with a device for analyzing
the material on the basis of the detected temperature increase as a
function of the wavelength of the excitation light beam and the
intensity modulation of the excitation light beam.
[0162] 19) The device according to aspect 18, characterized in that
the excitation light source is directly fixedly mechanically
connected to the optical medium.
[0163] 20) The device according to aspect 18, characterized in that
a device is provided for emitting a measurement light beam into the
region of the optical medium which is in contact with the first
region of the material surface, and that in order to detect the
measurement light beam this device and/or the detection device is
directly fixedly mechanically connected to the optical medium
and/or coupled thereto by means of a fibre-optic cable.
[0164] 21) The device according to aspect 18, 19 or 20,
characterized in that the optical medium directly supports an
imaging optics and/or that an imaging optics is integrated into the
optical medium.
[0165] 22) The device according to aspect 18 or any of the other
preceding or following aspects, characterized in that the surface
of the optical medium has a plurality of partial faces inclined
towards each other, at which the measuring light beam is reflected
multiple times.
[0166] 23) The device according to aspect 18 or any of the other
preceding or following aspects, characterized in that one or more
mirror surfaces are provided in or on the optical medium for
reflection of the measuring light beam.
[0167] 24) The device according to aspect 16 or 17, characterized
in that in order to detect a time-dependent response signal, the
detection device has an acoustic detector for detecting acoustic
waves on the material surface, in particular with a resonator, more
particularly with a Helmholtz resonator. As the detector of the
acoustic source a quartz fork is used, preferably with the same
resonance frequency as the resonator. The resonator can be open or
closed. The quartz fork is preferably in or on the neck of the
resonator (off-beam) or inside or outside of the resonator
(in-beam).
[0168] 25) The device according to aspect 16, 17 or 18,
characterized in that in order to detect a time-dependent response
signal, the detection device has a thermal radiation detector for
detecting the heat radiation at the material surface, in particular
an infrared detector, more particularly a thermocouple, a
bolometer, or a semiconductor detector.
[0169] 26) The device according to any one of the aspects 16 to 25,
characterized in that the excitation light source and the detection
device are directly attached to each other or to a common support,
which is formed in particular by a housing or housing part of the
device.
[0170] 27) The device according to any one of the aspects 16 to 26,
characterized in that the device has a wearable housing which can
be fastened to the body of a person, wherein the device for
emitting one or more excitation light beams and the detection
device for detecting a time-dependent response signal are arranged
and configured in such a way that the material to be analyzed is
measured on the side of the housing facing away from the body.
[0171] 28) The device according to any one of the aspects 16 to 26,
characterized in that the device has a wearable housing, which can
be fastened to the body of a person, and that the housing of the
device has a window which is transparent for the excitation light
beam on its side facing away from the body in the intended wearing
position.
[0172] 29. A device for analyzing a material with an excitation
transmission device for generating at least one electromagnetic
excitation beam, in particular an excitation light beam, with at
least one excitation wavelength, a detection device for detecting a
response signal and a device for analyzing the material on the
basis of the detected response signal.
[0173] 30. The device according to any one of the preceding aspects
16 to 29, characterized in that the detection device is configured
for measuring the deformation of a crystal.
[0174] The deformation can be measured more effectively by analogy
with the photothermal `Bouncing method` by the selection of steeper
(larger) angles of incidence of the measuring beam to the sample
surface and the influence of the mirage effect-related deflection
of the measuring beam can be minimized.
Literature
[0175] M. Bertolotti, G. L. Liakhou, R. Li Voti, S. Paolino, and C.
Sibilia. Analysis of the photothermal deflection technique win the
surface refection theme: Theory and Experiment. Journal of Applied
Physics 83, 966 (1998)
[0176] A cantilever can be placed either directly on the sample or
on a sufficiently thin optical medium, on which the sample is
placed on the one side and the cantilever on the opposite side. Due
to the thermal expansion of the sample or the optical element, the
cantilever is set into vibration by the thermal expansion caused by
the absorption of the modulated pumped beam. The measuring beam is
reflected onto the upper side of the tip of the cantilever and is
deflected due to the vibration, by an amount depending on the
irradiated wavelength and the thermal properties of the sample, and
on the modulation frequency. This deflection is detected.
[0177] 31. The device according to any one of the preceding aspects
16 to 30, characterized in that the excitation transmission device
contains an interrogation laser or an LED, for example an NIR
(near-infrared) LED.
[0178] 32. The device according to any one of the preceding aspects
16 to 31, characterized in that the excitation transmission device
comprises a probe laser, which has a smaller diameter than an
additional pump laser.
[0179] 33. The device according to any one of the preceding aspects
16 to 32, characterized in that in order to achieve a more
favorable signal-to-noise ratio, a special coating, in particular
of the optical emitter, for example IRE is provided, so that heat
is dissipated better (e.g. "thermal conducting paste").
[0180] The optical element can be coated on the contact surface in
such a way that an improved conduction of the thermal signal into
the optical medium can be provided. In addition, the coating can
also serve as protection against scratches, and by intelligent
choice of material can also implement a reflective surface for the
measuring beam. In this case, the transparency for the excitation
light must be maintained.
[0181] 34. The device according to any one of the preceding aspects
16 to 33, characterized in that the device has a system for [0182]
i. pulse trains/double modulation [0183] ii. oscillating mirror
[0184] iii. MEMS interferometer.
[0185] 35. The device according to any one of the preceding aspects
16 to 34, characterized in that the device is designed to be
permanently wearable by a person on the body, in one embodiment by
means of a retaining device connected to the housing, such as a
belt, a band or a chain or a clasp, and/or in that the detection
device has a detection surface, which can also be used as a display
surface for information such as measurement values, clock times
and/or textual information.
[0186] 36. The device according to the preceding aspect 35,
characterized in that the device has a pull-off film in the area of
the detection surface, preferably next to the detection surface,
for the pre-treatment of the material surface and for ensuring a
clean surface and/or which in one embodiment in the case of glucose
measurement, is specifically provided for the purpose of skin
cleansing.
[0187] 37. The device according to any one of the preceding aspects
16 to 36, characterized in that the detection device is configured
to read and recognize fingerprints to retrieve certain
values/calibrations of a person and/or to detect the location of a
finger, preferably to detect and determine an unintended movement
during the measurement.
[0188] 38. The device according to any one of the preceding aspects
16 to 37, characterized in that the detection device has a results
display, which is implemented, preferably with color coding, as an
analogue display, in one embodiment including an error indication
(for example: "100 mg/dl plus/minus 5 mg/dl"), acoustically and/or
with a result display of measurements in larger steps than the
accuracy of the device allows. This means that, for example, small
fluctuations which could unsettle a user are not communicated.
[0189] 39. The device according to any one of the preceding aspects
16 to 38, characterized in that the device comprises data
interfaces for the transfer of measured data and the retrieval of
calibration data or other data from other devices or cloud systems,
wherein the device is preferably configured in such a way that the
data can be transmitted in encrypted form, in particular can be
encrypted by fingerprint or other biometric data of the
operator.
[0190] 40. The device according to any one of the preceding aspects
16 to 39, characterized in that the device is configured in such a
way that a proposed insulin dose to be given to a person can be
determined by the device in conjunction with other data (e.g.
insulin correction factor) and/or weight, body fat can be measured
and/or manually specified at the same time or can be transmitted
from other devices to the device.
[0191] 41. The device according to any one of the preceding aspects
16 to 40, characterized in that in order to increase the
measurement accuracy, the device is configured to identify further
parameters, in one embodiment using sensors for determining the
skin temperature, diffusivity, conductivity/moisture level of the
skin, for measuring the polarization of the light (secretion of
water/sweat on the finger surface) or such like.
[0192] Water and sweat on the skin surface of a person, which can
influence the glucose measurement, can be detected by a test
stimulus with an excitation radiation using the excitation
transmission device with the water-specific bands at 1640 cm-1 (6.1
.mu.m) and 690 cm-1 (15 .mu.m). If the absorption should exceed a
certain value, the measurement site/material surface/skin surface
is too wet for a reliable measurement. Alternatively, the
conductivity of the substance in the vicinity or directly at the
measurement site can be measured, in order to determine the
moisture level. An error message and an instruction to dry the
surface can then be output.
[0193] 42. The device according to any one of the preceding aspects
16 to 41, characterized in that the device has a cover in the beam
path of the pumping and/or measuring beam laser. This ensures the
compulsory eye safety for human beings is provided.
[0194] 43. The device according to any one of the preceding aspects
16 to 42, characterized in that the device has a replaceable
detection surface.
[0195] 44. The device according to any one of the preceding aspects
16 to 43, characterized in that the device is provided in some
areas with a grooved or roughened crystal as an optical medium,
which allows a better adjustment of the sample (e.g. the finger).
The measuring point, on which the surface of the material to be
analyzed is placed, is preferably designed without grooves and
smooth.
[0196] 45. The device according to any one of the preceding aspects
16 to 44, characterized in that for the measuring beam either a
cylindrical TEMpl TEM00 mode can be used, or other modes can be
used instead of the cylindrical TEMpl TEM00 mode, e.g. TEM01
(Doughnut), TEM02 or TEM03. Particularly the latter modes have the
advantage that their intensity can be matched to the sensitivity
profile of the quadrant diode, which forms the detector for the
deflected measuring beam (see figures). In addition, rectangular
modes TEMmn can be used, such as TEM30 or TEM03 or higher. This
allows sampling/measuring beams to be used which are less prone to
interference in the horizontal or vertical direction.
[0197] 46. The device according to any one of the preceding aspects
16 to 45, characterized in that the device measures not only at a
point but in a grid. This can be done either by displacing the
pumped or probe laser or the detection unit. Instead of a
displacement, one or more arrays of pumping or probe lasers are
possible.
[0198] Other detection methods for the detection of a response
signal after emission of an excitation beam may comprise: [0199]
photo-acoustic detection--photo-acoustic detection using a tuning
fork or other vibration element or: a slightly modified form of
photo-acoustics with an open QePAS cell (Quartz-enhanced
Photo-Acoustic Spectroscopy). These methods can be used to detect
pressure fluctuations/vibrations on the surface and evaluate them
in the manner described above for the measured beam deflection.
[0200] In principle, measured values of a phase shift of the
response signal relative to a periodic modulation of the excitation
beam can be used for depth profiling. (To this end, warming/cooling
phases of the material surface should be more accurately evaluated
with regard to their waveform or pattern.)
[0201] The device described can be associated with a supply of
adhesive strips for removing dead skin layers, in order to allow a
maximally undistorted measurement on a human body, as well as
plasters with thermal conductive paste that can be applied to the
optical medium on a regular basis. The optical medium can be
replaceable, given suitable fastening and adjustment of the
remaining parts.
[0202] To perform the measurement, the device can be provided and
configured not only on a person's finger, but also on a lip or an
earlobe.
[0203] In some embodiments the measurement can work even without
direct contact and placement of the finger or other part of the
body (at a distance), resulting in a contact-free measurement.
[0204] The measurement can be improved with regard to its accuracy
and reliability by combination of a plurality of the measuring
systems described and explained, with similar susceptibility to
error.
[0205] DAQ and lock-in amplifiers in the evaluation can be combined
in one device and overall the evaluation can be digitized.
[0206] The measuring device can also be performed on a moving
surface, so that in the course of a grid measurement: excitation
light source and and/or measuring light source move over the skin
in a grid pattern during the measurement, which allows skin
irregularities to be compensated for or even eliminated.
[0207] The sensitivity of the detection device/deflection unit can
be optimized by adjustment/variation of the wavelength of the probe
beam/measurement light source. For this purpose, the measurement
light source can be varied with respect to wavelength or else
contain a plurality of laser light sources at different wavelengths
for selection or combination.
[0208] For the deflection of the pump/probe laser an ideal
transverse mode (TEM) can be selected.
[0209] The excitation transmission device, measuring light source
and detector can be configured as a common array and the beams can
be suitably deflected in the optical medium to concentrate the
emission and reception of all beams at one point.
[0210] A lens on or in the crystal of the optical medium can
contribute to deflecting the measuring light beam more strongly
depending on the response signal.
[0211] In addition, it is conceivable to use a gap-free photodiode
for the detection, and a lens could then focus the measuring light
beam after its exit, to thus enable a more accurate
measurement.
[0212] An additional variant of the invention, in accordance with
the patent claims is described in the following concept. This
concept, whether taken alone, in combination with the above aspects
or with the subject matter of the claims, also constitutes at least
one independent invention. The applicant reserves the right to make
this invention or these inventions the subject of claims at a later
date. This can be done either in the context of this application or
else in the context of subsequent divisional applications or
continuation applications claiming the priority of this
application:
[0213] A concept for non-invasive blood sugar measurement by a
determination of the glucose in the skin by means of excitation
using quantum-cascade lasers and measurement of the thermal wave by
radiant heat. On the basis of FIGS. 12 and 13 a method is described
with which the concentration of the glucose or another material in
the interstitial fluid (ISF) in the skin can be determined. Glucose
in the ISF is representative of blood glucose and follows it
rapidly in the event of changes. The method consists of at least
individual steps or groups of the following steps or of the entire
sequence:
1. The point on the skin 102 (in this case, the first region of the
material surface), is irradiated with a beam of a quantum cascade
laser, which is focused and possibly reflected at a mirror or
parabolic mirror 140, and which is incrementally or continuously
tuned over a specific infrared range, in which glucose is
specifically absorbed. Instead of the quantum cascade laser 100, a
laser array with a plurality of lasers radiating at single
wavelengths can also be used. The spectral range (or the individual
wavelengths, typically 5 or more wavelengths) can be in particular
between approximately 900 and approximately 1300 cm.sup.-1, in
which glucose has an absorption fingerprint, that is to say,
typical and representative absorption lines. 2. The excitation beam
designated with SA is employed continuously (CW lasers) or in
pulsed mode with a high pulse repetition rate or in a modulated
manner. In addition, the excitation beam is low-frequency
modulated, in particular in the frequency range between 10 and 1000
Hz. The low-frequency modulation can be performed with a variety of
periodic functions, in various embodiments sine-wave, square wave
or sawtooth wave, or the likes. 3. Due to the irradiation of the
skin the IR-radiation penetrates the skin to a depth of roughly
50-100 .mu.m and--depending on the wavelength--excites specific
vibrations in the glucose molecule. These excitations from the
vibration level v0 to v1 return to the initial state within a very
short time; in this step heat is released. 4. As a result of the
heat produced according to (3) a thermal wave is formed, which
propagates isotropically from the place of absorption. Depending on
the thermal diffusion length, defined by the low-frequency
modulation described in (2) above, the thermal wave reaches the
surface of the skin periodically at the modulation frequency. 5.
The periodic emergence of the thermal wave at the surface
corresponds to a periodic modulation of the thermal radiation
property of the skin (material surface of the sample). The skin can
be described here approximately as a black body radiator, whose
entire emission according to the Stefan-Boltzmann law is
proportional to the fourth power of the surface temperature. 6.
With a detector 139 for heat radiation, i.e., an infrared detector,
i.e. a thermocouple, bolometer, semiconductor detector or similar
device, which is directed at the point of the skin under
irradiation, the periodic temperature increase described under (5)
is recorded. It depends on the irradiation of infrared light
described under (1) and (2), and on the absorption described under
(3), and therefore depends on the concentration of glucose. The
thermal radiation SR (in this case, the response signal) is
collected by means of an optical element, in one embodiment an
infrared lens or a minor, in particular a concave parabolic mirror
141, and, in one embodiment is directed via a convex minor 141a on
to the detector 139. For this purpose a collection minor used in
one embodiment can have an opening 142, through which the collected
beam is directed. A filter 143 can also be provided in the beam
path, which only allows infrared radiation of a certain wavelength
range to pass. 7. In processing the response signals, the
modulation frequency can be specifically taken into account, for
which the response signal can be processed in a lock-in amplifier
144. By analysis of the phase angle between the excitation signal
and heat radiation signal (response signal) using a control and
processing unit 147, the depth information relating to the depth
below the surface can be obtained, from which the response signals
are largely obtained. 8. The depth information can also be obtained
by the selection and analysis of various low-frequency modulation
frequencies as described in (2) for the excitation beam and the
combination of the results for different modulation frequencies
(wherein the results can also be weighted differently for different
modulation frequencies). Difference methods or other calculation
methods can be used for this, to compensate for the absorption of
the topmost skin layers. 9. To maximize the sensitivity in the
detection of the thermal radiation according to point (6), it is
used over a broad spectral band for the entire available infrared
range. As many regions of the Planck radiation curve as possible
should be used. To make the detection insensitive to the intensive
excitation radiation, the detection of the heat radiation is
provided with blocking filter (notch filter) 143 for these
excitation wavelengths. The wavelength range 148 transmitted
through the blocking filter 143 is also apparent from the diagram
of FIG. 13. Therein, the intensity of the response signal is shown
both as a function of the wavelength, in a first (solid) curve 145
without an excitation beam or only with excitation radiation in
non-specific wavelengths for the material to be identified (i.e.
without the wavelengths where specific absorption bands of the
material exist), and then in a second (dashed) curve 146 a similar
curve is shown, wherein an excitation beam is irradiated which
contains specific absorption wavelengths of the material to be
identified. 10. From the thermal signal measured according to
(6-9), which is dependent on the excitation wavelength, if glucose
is to be identified, in one embodiment the background is determined
first with non-glucose-relevant wavelengths (or excluding them) of
the excitation beam (curve 145), and then with (or including) the
glucose-relevant wavelengths the difference from the background
signal is determined. This results in the glucose concentration in
the skin layer or skin layers, which are defined by the selected
phase position according to (7) or the different modulation
frequencies according to (8) or a combination of these.
[0214] Although the invention has been illustrated and described in
greater detail by means of preferred exemplary embodiments, the
invention is not limited by the examples disclosed and other
variations can be derived therefrom by the person skilled in the
art without departing from the scope of protection of the
invention.
LIST OF REFERENCE NUMERALS
[0215] 10 device
[0216] 100 excitation transmission device/excitation light
source
[0217] 100a emitters/transmission elements
[0218] 101 material
[0219] 102 first region
[0220] 103 volume
[0221] 104 device
[0222] 105 device
[0223] 106 detection device
[0224] 107 processing device/evaluation device
[0225] 107a memory
[0226] 108 optical medium
[0227] 108a surface section
[0228] 108b surface section
[0229] 109 adjustment device
[0230] 110 partial surface
[0231] 111 partial surface
[0232] 112 measuring beam/measuring light beam
[0233] 113 mirror surface
[0234] 114 minor surface
[0235] 116 opening
[0236] 117 opening
[0237] 118 opening
[0238] 119 connector body
[0239] 120 fibre-optic cable
[0240] 121 support
[0241] 122 housing
[0242] 123 body
[0243] 124 side
[0244] 125 belt
[0245] 126 fingertip
[0246] 127 adjustment device
[0247] 128 imaging optics
[0248] 129 imaging optics
[0249] 130 optical detector/camera
[0250] 131 data processing device
[0251] 132 controller
[0252] 133 micro-mirror
[0253] 134 micro-mirror
[0254] 135 micro-electro-mechanical system
[0255] 136 deflection device
[0256] 137 control device
[0257] 138 layer
[0258] 139 infrared detector
[0259] 140 mirror
[0260] 141 parabolic mirror
[0261] 142 opening in 141
[0262] 143 wavelength filter
[0263] 144 lock-in amplifier
[0264] 145 signal curve of the response signal (solid line)
[0265] 146 signal curve of the response signal (dashed line)
[0266] 147 control and processing device
[0267] 148 wavelength range
[0268] BZA blood sugar level indication
[0269] D detection result
[0270] GF interface
[0271] SA excitation beam
[0272] SR response signal
* * * * *