Apparatus and method for sensing features of an object, in particular biological tissue

Abstract

The disclosure relates to an apparatus for sensing features of an object (1), in particular biological tissue, the apparatus comprising a perturbation device (4) configured to apply a perturbation, in particular a temporary perturbation, to a region of interest of the object (1), an irradiation device (5) configured to irradiate the region of interest, to which the perturbation is being and / or has been applied, with electromagnetic radiation (6), and a detection device (7) configured to detect a response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation (6). The apparatus further comprises a processor (8) configured to derive, on the basis of the response signal, information characterizing at least one feature of the object (1).

Description

[0001] 120856P785PC

[0002] Apparatus and Method for Sensing Features of an Object,

[0003] in particular Biological Tissue

[0004] Description

[0005] The present disclosure relates to an apparatus and a method for sensing features of an object, in particular of biological tissue.

[0006] Metabolite monitoring can play a critical role in many diseases, including cancer and car-dio-metabolic diseases such as diabetes and cardiovascular disease. Similarly, metabolite monitoring is expected to play an increasingly important role in personalized and precision medicine and interventions, from monitoring food metabolism and physical activity to the effects of lifestyle, drug efficacy or disease occurrence and progression. In addition to metabolites, the measurement of functional and morphological parameters can also provide important information about the state of the cardiovascular system. Similarly, such measurements can be applied to a variety of other diseases and conditions and even to nonmedical matters, from dermatological diseases, systemic diseases and wound healing applications to the assessment of pollutants, nutrients (e.g. vitamins) or contaminants (e.g. toxins) in the body, food, liquids and water, as well as in the environment.

[0007] It is an object of the present disclosure to provide an improved apparatus and method, and a corresponding computer program product, for sensing features of an object, in particular of a biological tissue, preferably with enhanced accuracy, sensitivity and / or specificity.

[0008] The object is achieved by an apparatus and method and corresponding computer program product according to the independent claims.

[0009] According to a first aspect, an apparatus for sensing features of an object, in particular a biological tissue, comprises a perturbation device configured to apply a perturbation, in particular a temporary perturbation, to a region of interest of the object, an irradiation device configured to irradiate the region of interest, to which the perturbation is being and / orhas been applied, with electromagnetic radiation, and a detection device configured to detect a response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation. The apparatus further comprises a processor configured to derive, on the basis of the response signal, information characterizing at least one feature of the object, in particular with respect to an effect of the perturbation on the at least one feature of the object.

[0010] According to a second aspect, a method for sensing features of an object, in particular a biological tissue, comprises the following steps: receiving and / or accessing a response signal which has been detected in response to irradiating a region of interest of the object, to which a perturbation, in particular a temporary perturbation, is being and / or has been applied, with electromagnetic radiation, and deriving, on the basis of the response signal, information characterizing at least one feature of the object, in particular with respect to an effect of the perturbation on the at least one feature of the object.

[0011] According to a third aspect, a computer program product comprising instructions causing a computer, in particular the apparatus according to the first aspect and / or the processor of the apparatus according to the first aspect, to execute the steps of: controlling the perturbation device to apply a perturbation, in particular a temporary perturbation, to a region of interest of the object; controlling the irradiation device to irradiate the region of interest, to which the perturbation is being and / or has been applied, with electromagnetic radiation; controlling the detection device to detect a response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation; and deriving, on the basis of the response signal, information characterizing at least one feature of the object, in particular with respect to an effect of the perturbation on the at least one feature of the object.

[0012] Aspects of the present disclosure are preferably based on the approach of controlling and / or influencing properties of an object of interest (OOI), for example a skin tissue or fruit, by means of a perturbation, such as a temporary mechanical and / or thermal manipulation of the object, while applying a measurement on the object, e.g. by detecting an optoacoustic or optical response of the object when excited and / or irradiated with electromagnetic energy. In this way, possible effects of the perturbation on the measured object and / or its features (e.g. metabolite content, functional and / or morphological parameters) can be identified and further used to determine or reveal, e.g., the state of the object or aparameter of the object such as the spectral appearance of the object or the density of the object with improved accuracy, sensitivity and / or specificity.

[0013] Preferably, the apparatus comprises a sensor which comprises the irradiation device and / or the detection device, and preferably also the perturbation device. Preferably, the apparatus and / or the sensor is designed and / or configured to be brought into contact with, e.g. placed on, the object.

[0014] Preferably, the perturbation device is configured to apply a mechanical perturbation to the region of interest, in particular by applying a negative and / or positive pressure to the region of interest. In this way, hypo or hyper pressure, respectively, can be applied to the region of interest. Optionally, the perturbation device is configured to apply cycles of pressure in which hypo and hyper pressure alternate.

[0015] Preferably, the perturbation device is configured to apply a suction to the region of interest and / or to apply a negative pressure (hypo-pressure) to the region of interest and / or to reduce a pressure at and / or in and / or above the region of interest below ambient pressure. Preferably, the processor is configured to derive, on the basis of the detected response signal emanating from the region of interest, to which the suction and / or negative pressure and / or pressure below ambient pressure is being and / or has been applied, information characterizing at least one feature of the object.

[0016] Preferably, in the context of the present disclosure, the terms “suction”, “negative pressure”, “hypo-pressure” or “pressure reduced below ambient pressure” are used synonymously, unless explicitly stated otherwise.

[0017] Due to resulting suction forces, the region of interest is drawn against a contact section of the apparatus and / or sensor (e.g. against a contact section of a sensor housing) which is adjacent to and / or in contact with the region of interest.

[0018] In this way, acoustic coupling between the region of interest and the sensor is improved which, in turn, improves the signal to noise ratio of detected ultrasound waves (response signal) in case of an optoacoustic detection or measurement of the region of interest’sresponse to an excitation and / or irradiation with pulsed electromagnetic radiation while and / or after applying the mechanical perturbation.

[0019] Further, applying suction and / or a negative pressure and / or a pressure below ambient pressure advantageously allows for deriving physiological values in response thereto, such as a (blood) perfusion change, a blood volume change and / or a rearrangement of physiological layers in the region of interest.

[0020] Specifically, applying suction and / or negative pressure may dilate blood vessels within the region (volume) of interest and / or shift these dilated vessels slightly toward the surface of the region of interest and / or the sensor and thereby increase the relative amount of blood-related information contained in the detected response signals.

[0021] Advantageously, the physiological values obtained in this way can themselves be used as medically relevant properties. For example, vascular responsiveness (e.g. dilatation and / or shift in response to suction and / or negative pressure, as exemplarily described above) can be used as an early indicator of diabetes. Alternatively or additionally, the physiological values can be used to assist and / or improve blood glucose estimation performance. Alternatively or additionally, deriving physiological values (e.g., blood volume change) can be advantageous for regression algorithms when estimating blood metabolite concentrations. In addition, the derived physiological response to suction may itself have medical significance.

[0022] In contrast to applying suction and / or negative pressure and / or reducing pressure below ambient pressure, applying positive pressure to the region of interest may tend to collapse superficial blood vessels and therefore reduce or even fully prevent perfusion in those vessels.

[0023] Preferably, the processor is configured to derive, on the basis of the detected response signal(s) emanating from the region of interest, to which the suction and / or negative pressure and / or the pressure below ambient pressure is being and / or has been applied, information characterizing at least one feature of the object, in particular with respect to an effect of the suction and / or negative pressure and / or pressure below ambient pressure on at least one feature of the object. In this way, possible effects of the suction and / or negativepressure and / or pressure below ambient pressure on the measured object and / or its features (e.g. metabolite content, functional and / or morphological parameters) can be identified and further used to determine or reveal, e.g., the state of the object or a parameter of the object with improved accuracy, sensitivity and / or specificity. This is particularly advantageous in applications which, e.g., are signal-limited by design, such as mid-IR detection (i.e. detecting acoustic waves in response to an irradiation with pulsed mid-IR irradiation) of in-blood metabolites, where a significant increase in sensitivity is possible by, preferably temporarily, increasing, e.g., the local blood volume by applying suction and / or negative pressure, and an optional subsequent normalizing to the steady state (where the suction and / or negative pressure is absent). This is in contrast to applying positive pressure and / or “pressing away” blood, which may occlude blood flow and / or prevent blood from remaining within the measurement volume (region of interest).

[0024] Preferably, the perturbation device comprises a fluid pump, in particular an air pump such as a vacuum pump or a water pump, configured to control, in particular to decrease, a fluid pressure, in particular a gas or liquid pressure, prevailing in a volume adjacent to the region of interest. Alternatively or additionally, the perturbation device comprises at least one movable piston and / or diaphragm and / or peristaltic pump configured to decrease a volume adjacent to the region of interest, resulting in a decrease in fluid pressure, in particular gas or liquid pressure, prevailing in the volume. Alternatively or additionally, the perturbation device comprises a temperature controller configured to control, in particular to decrease, the temperature of a fluid, such as air and / or a gaseous or liquid coupling medium, such as water and / or ultrasound gel, contained in a volume adjacent to the region of interest, thereby controlling, in particular decreasing, the fluid pressure, in particular gas or liquid pressure, prevailing in the volume These examples, alone or in combination, enable the application of a mechanical perturbation, in particular a suction and / or negative pressure and / or a pressure below ambient pressure, to the region of interest in a simple and precise manner.

[0025] Preferably, the perturbation device is configured to apply a thermal perturbation to the region of interest, in particular by modifying and / or modulating the temperature of the region of interest.

[0026] Preferably, the application of mechanical and thermal perturbation(s) to the region of interest can be combined, in particular to advantageously reveal broader information aboutthe object of interest compared to applying “stand-alone” or “pure” mechanical or thermal perturbations. It is, therefore, particularly preferred that the perturbation device is configured to apply, in combination and / or simultaneously with the suction and / or negative pressure and / or pressure below ambient pressure, a thermal perturbation to the region of interest, in particular by modifying and / or modulating the temperature of the region of interest. Preferably, the processor is configured to derive, on the basis of the detected response signal emanating from the region of interest, to which both i) the suction and / or negative pressure and / or pressure below ambient pressure and ii) the thermal perturbation are being and / or have been applied, information characterizing at least one feature of the object, in particular with respect to an effect of the i) suction and / or negative pressure and / or pressure below ambient pressure ii) the thermal perturbation on the at least one feature of the object. The simultaneous application of a suction and / or negative pressure perturbation and temperature perturbation, along with a detection of the corresponding response signals, may represent a kind of “optimum” or “sweet spot” in terms of physiological effect, energy consumption, and minimizing user discomfort caused by the perturbation(s).

[0027] It is noted that, due to adiabatic cooling / heating resulting from a change in pressure, there may be some coupling (or correlation) between pressure and temperature, e.g. a decrease in pressure in a gas volume adjacent to the region of interest may also result in a decrease in the temperature in the gas volume. Although the resulting conducted temperature change in the tissue may be small, the surrounding gas / atmosphere can experience a noticeable temperature change. Therefore, it may be preferred that the perturbation device is configured to apply the suction and / or negative pressure to the region of interest and / or to reduce the pressure below ambient pressure by means of adiabatic, or at least approximately or substantially adiabatic, expansion of the gas volume adjacent to the region of interest.

[0028] Preferably, the perturbation device comprises at least one thermoelectric element, in particular a thermocouple or Peltier element, configured to be brought into contact with the region of interest to increase and / or decrease the temperature of the region of interest.

[0029] Alternatively or additionally, the perturbation device comprises an infrared radiation source configured to irradiate the region of interest with infrared radiation to increase the temperature of the region of interest. In this way, electromagnetic radiation (laser and / or IR radiation) is used to induce temperature changes directly in the tissue, preferably in a non-contact manner and not via coupling medium, to induce physiological changes. The radiation might be a CW laser or light source. This should not be confused with optoacoustic excitation with pulsed radiation.

[0030] Alternatively or additionally, the perturbation device comprises an ultrasound wave source configured to couple high intensity focused ultrasound waves (HIFU) into the region of interest to generate heat at a focal zone of the focused ultrasound waves.

[0031] These examples, alone or in combination, enable the application of a thermal perturbation to the region of interest in a precise and reliable manner.

[0032] Preferably, the detection device is configured to detect the response signal emanating from the region of interest over time, in particular after the suction and / or negative pressure and / or pressure below ambient pressure and / or the thermal perturbation have been applied, to obtain a temporal course of the response signal representing the temporal course of a physiological effect in the region of interest resulting from the pressure, and optionally temperature, perturbation. Preferably, the processor is configured to derive information characterizing at least one feature of the object and / or region of interest based on at least one of the following: i) a rate of change characterizing a ratio of a change of the response signal per unit of time, and / or ii) a time to maximum characterizing a period of time it takes for the response signal starting from an initial signal, also referred to as “onset”, to reach its maximum, and / or iii) a time integral of the response signal, in particular over a period of time between an initial signal (onset) and a maximum of the response signal.

[0033] The above embodiment is based on the approach of considering the response kinetics (i.e. the kinetics of the region of interest’s or object’s response to pressure and / or thermal perturbations)) to derive properties and / or parameters characterizing the object and / or the region of interest. Preferably, after pressure and / or thermal perturbation steps (or perturbation peaks), one or more of the above-mentioned metrics (i.e. rate of change, time to maximum, time integral of response signal) are assessed and / or considered to derive the desired information. Advantageously, by using the response kinetics metrics, the measurement inherently corrects for inaccuracies in absolute physiological properties, making it more resilient to external or parasitic influences on the measurement. Further, the re-sponse kinetics values themselves can be medically useful metrics (e.g., vascular response dynamics indicating disease state or symptom severity, such as endothelial dysfunction). Last but not least, deriving the desired information from a time series (i.e. the time course of the response signal(s)) yield more robust results with respect to baseline variability, so that effects of skin thickness, skin contamination, and sensor drift can be reduced or partially compensated.

[0034] Preferably, the perturbation device is configured to apply the perturbation to the region of interest by applying and / or administering at least one chemical or drug to the region of interest. For example, a substance increasing blood volume can be applied to the region of interest or administered to the object. Preferably, applying or administering the at least one chemical or drug may be combined with applying a mechanical and / or thermal perturbation to the region of interest. However, it is also possible to apply or administer at least one chemical or drug to the region of interest instead of applying a mechanical and / or thermal perturbation.

[0035] Preferably, the apparatus and / or sensor is configured to collect or detect the response signal at at least one point in time (also referred to as “temporal point” hereinafter), during or after the perturbation.

[0036] In a preferred embodiment, the apparatus and / or sensor collects the response signal at at least two points over time, before, during and / or after each perturbation applied.

[0037] Preferably, when at least two points are detected, then the measurement at one temporal point may be used as reference or used to modify a measurement at a second temporal point.

[0038] For example, a measurement (i.e. a response signal detected) at a low pressure or temperature point may be subtracted from a measurement (i.e. a response signal detected) at a high-pressure or temperature point.

[0039] Preferably, more generally, a function of the measurements at at least one temporal point can be employed to modify the function of the measurements at at least another temporal point.Preferably, the use of at least two measurements temporal points can normalize one measurement to the other measurement in order to remove the effects of the background medium from the resulting measurement.

[0040] More generally, the points collected are preferably employed as part of a computational scheme, which may be deterministic or a trained model, for example a deep learning, machine learning or Al model, to improve an aspect of the apparatus output based on any subset of the measurements collected.

[0041] Preferably, response signals at a series of temporal points can be likewise detected over time to capture cycles of a repeated or periodic application of the perturbation.

[0042] Preferably, the perturbation device and / or the processor and / or a computer program acting as a controller of the operation of the device is adapted to apply the perturbation in a way that it depends on another external signal, for example arterial pulsation which can be considered as an “internal perturbation” of the object.

[0043] Preferably, the operation of the perturbation can then be synchronous to the external signal (characterizing an “internal perturbation”), have a delay to the external signal or relate to the external signal in another predetermined way.

[0044] Preferably, the external signal can be collected by another sensor and fed into the perturbation device and / or the processor.

[0045] In an embodiment of an apparatus and method according to an alternative aspect of the present disclosure, the perturbation device does not necessarily have to be configured to apply an “external” perturbation to the region of interest of the object (i.e. a pressure and / or thermal perturbation being induced from outside the object), but rather to sense naturally occurring internal perturbations of the object, such as cardiac or respiratory cycles. In this case, the processor is preferably configured to control the irradiation device and / or the detection device such that the detection of the response signal(s) emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation is (or are) is controlled and / or synchronized and / or gated and / or triggered by the naturally occurring internal perturbations of the object. In other words, in this embodimentthe perturbation device just provides an external signal (characterizing an “internal perturbation”) to operate the sensing or detecting function of the apparatus, without necessarily applying an “external” perturbation.

[0046] According to a preferred embodiment of the present disclosure, the processor is configured to receive an external signal characterizing at least one naturally occurring internal perturbation of the region of interest, in particular a cardiac or respiratory cycle of the object. Preferably, the processor is further configured to control the perturbation device such that the application of the suction and / or negative pressure and / or pressure below ambient pressure and / or the thermal perturbation to the region of interest is controlled and / or synchronized and / or gated and / or triggered by the at least one naturally occurring internal perturbation of the object. Alternatively or additionally, the processor is further configured to control the irradiation device and / or the detection device such that the detection of the response signal(s) emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation is (are) controlled and / or synchronized and / or gated and / or triggered by the at least one naturally occurring internal perturbation of the object. Preferably, the processor is further configured to derive information characterizing at least one feature of the object, based on the response signal resulting from the perturbation and / or detection which was (were) controlled and / or synchronized and / or gated and / or triggered by the at least one naturally occurring internal perturbation of the object.

[0047] Preferably, the external signal may be provided by a separate sensor which is configured to detect or measure the naturally occurring internal perturbation(s) of the object, for example the heart rate, cardiac and / or respiratory cycle(s) of the object. Alternatively, the perturbation device can be configured accordingly to detect or measure the naturally occurring internal perturbation(s).

[0048] Advantageously, synchronizing the response signal detection to naturally occurring internal perturbations may reduce (or even eliminate) the need for applying external perturbations such as suction and / or negative pressure and / or temperature. Further, by synchronizing the application of an external perturbation with the internal perturbation, the required amount or magnitude of the applied external perturbation may be lower - or even zero -from the outset. This may result in less technical effort (cost-effective components), lower energy consumption, smaller form factors, lower component cost, longer battery operationfor the same battery capacity, and / or smaller battery volume and weight for the same runtime, less (or even no) reduction in user comfort, since less (or even no) external perturbation is required, quieter or even completely silent operation. Additionally, motion artifacts can be reduced by synchronizing to internal perturbations. Further, gating measurements to useful time windows can make acquisition more efficient (due to fewer repetitions and / or less required integration time), resulting in shorter measurement time and reduced energy consumption - again with downstream economic and usability implications (smaller battery resulting in smaller form factor resulting in lower cost and / or better usability).

[0049] Preferably, the timepoint or state of the (natural and / or internal) perturbation is provided by the source of the external signal, for example pressure or blood volume changes due to blood pulsation.

[0050] Preferably, the apparatus can be adapted to collect the response signal(s) at at least one point in time within the cycle indicated by the external signal, for example the pulsation cycle.

[0051] Preferably, the apparatus is configured to collect the response signal(s) at at least two points within the cycle indicated by the external signal.

[0052] Preferably, when at least two points are detected, then the measurement (i.e. the response signal detected) at one temporal point may be used as reference to modify a measurement (i.e. the response signal detected) at a second temporal point.

[0053] For example, a measurement at a low pressure or temperature point may be subtracted from a measurement at a high-pressure or temperature point during the pulsation cycle.

[0054] More generally, a function of the measurements at at least one temporal point can preferably be employed to modify the function of the measurements at at least another temporal point.

[0055] Preferably, such use of at least two measurement temporal points can normalize one measurement to the other measurement in order to remove the effects of the background medium from the resulting measurement.Preferably, a series of temporal points can be likewise detected over time to capture repeated cycles of the intrinsic perturbation.

[0056] Preferably, the irradiation device comprises a radiation source configured to irradiate the region of interest, to which the perturbation is being and / or has been applied, with timevarying, in particular pulsed, electromagnetic radiation. Preferably, the detection device comprises at least one ultrasound transducer configured to detect, as the response signal, ultrasound waves emanating from the region of interest in response to irradiating the region of interest with the time-varying, in particular pulsed, electromagnetic radiation. In this way, a so-called optoacoustic measurement, also termed photoacoustic, is implemented which is particularly useful for determining the presence and / or concentration of e.g. metabolites and other biomolecules and / or measuring functional and morphological parameters of the object of interest.

[0057] Preferably, the detection device comprises at least one radiation detector configured to detect, as the response signal, electromagnetic radiation. Preferably, the electromagnetic radiation may be reflected and / or scattered, in particular by Raman scattering, radiation and / or fluorescent radiation, emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation. In this way, an optical measurement is implemented, which can be used in addition to, complementary to or as an alternative to the optoacoustic measurement to determine properties and / or parameters of the object of interest.

[0058] Preferably, the perturbation device is configured to apply the perturbation repeatedly, in particular periodically and / or cyclically, to the region of interest of the object, and the detection device is configured to detect the response signal emanating from the region of interest in response to irradiating the region of interest, to which the perturbation is being and / or has been applied repeatedly, with the electromagnetic radiation. For example, the perturbation device may be configured to apply pressure cycles in which hypo and hyper pressure over the region of interest alternate cyclically and / or periodically, or to apply temperature cycles where the temperature of the region of interest increases and decreases cyclically and / or periodically.Preferably, the parameter and / or property of interest can be studied under these changing conditions. For example, aspects of microvasculature functionality can be measured due to a cyclic or periodic pressure perturbation, e.g. by conducting a measurement through the perturbation and resolving how the parameter of interest changes, e.g. how vessels dilate and constrict due to the perturbation. Such measurements may contain information that can separate health from disease, for example cardiovascular disease, and be used for various medical purposes such as early disease detection or monitoring progression and effect of interventions. Likewise, when monitoring food, such perturbations can reveal aspects of water content, ripeness, quality etc. Such perturbation(s) can also help concentrate a metabolite of interest under the point of energy deposition and measurement, thus improving the sensitivity, specificity and accuracy of the measurement. For example, an increase in pressure or temperature may dilate blood vessels or provide similar changes under the area where energy is deposited and signal generated, therefore providing a larger target (volume) wherein to measure a metabolite of interest.

[0059] Preferably, the processor is configured to derive, on the basis of the response signal emanating from the region of interest, to which the suction and / or negative pressure and / or pressure below ambient pressure and / or the thermal perturbation and / or the internal perturbation, is being and / or has been applied, at least one of the following information, by which one or more features of the object is characterized: i) the presence and / or concentration of at least one molecule of interest in the object, in particular at least one metabolite such as glucose, cortisol, troponin, lactate or fructose in tissue and / or at least one lipid such as omega-3 and omega-6 lipids, proteins and / or carbohydrates and / or water in food, plants or tissue, and / or ii) the presence, density and / or functionality of at least one structural component of the object, in particular a functionality such as a dilatation and / or constriction behavior of a microvasculature in the object in response to the perturbation, and / or iii) the spectral appearance of the object, and / or iv) the density of the object, and / or v) the position of a surface of the object relative to the irradiation device and / or detection device. Any of these derivations can be the output of the apparatus and / or processor.

[0060] Preferably, the processor is configured to derive, from the information characterizing one or more features of the object, i) diagnostic information characterizing a state of health of an individual (if the object is an individual), or ii) information characterizing at least one of a water content, ripeness and / or quality of food (if the object is food, such as a plant and / or fruit). Any of these derivations be the output of the apparatus and / or processor.Preferably, the detection device is configured to detect the response signal emanating from the region of interest over time, and the processor is configured to select a portion of the response signal, which has been detected during a specified time gate corresponding to a volume or layer in the object, and to derive the information characterizing at least one feature of the object on the basis of the selected portion of the response signal. This example, which is also referred to as “time-gating" or “depth gating”, is preferably employed to detect optoacoustic signals from different depths the object and / or to “read” optoacoustic signals from specific volumes in tissues. Such methods help to retrieve signals from deeper in tissue, i.e. under the object of interest’s (OOI) surface, gaining access to particular 001 compartments where the property of interest is abundant or concentrated. Preferably, time-gating techniques can be employed to reject non-specific contributions from the surface of the OOI and possibly read from depths rich in vasculature, better representing measurements in-blood. In this way, properties of interest such as glucose, troponin and lactate can be detected not only by using their particular spectral absorption signature but also in the so-called fingerprint region within the OOI.

[0061] Preferably, the perturbation device may also comprise an ambient temperature and / or an ambient humidity control, aiming to maintain similar conditions on the surface of the target measured. Termed “secondary control”, this process could comprise a flow circulating system, circulating air or fluid of a certain temperature and / or humidity, so as to dry or change the temperature of the measured object, in order to compensate for the effects of the perturbation.

[0062] Preferably, the processor is configured to control the apparatus to implement a closed-loop feedback mechanism as follows: In a step a), at least one property of the perturbation, in particular a speed and / or a frequency and / or an amplitude of the perturbation, is adapted dependent on a previously detected response signal and / or on the information derived from the previously detected response signal, whereby an adapted perturbation is obtained. In a step b), the perturbation device applies the adapted perturbation to the region of interest of the object, and in a step c), the irradiation device irradiates the region of interest, to which the adapted perturbation is being and / or has been applied, with the electromagnetic radiation, and / or the detection device detects an adapted response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation. Optionally, the steps a) to c) can be repeated one or more times.Preferably, the information characterizing at least one feature of the object is derived from the adapted response signal.

[0063] Further advantages, features and examples of the present disclosure will be apparent from the following description of following figures, wherein:

[0064] Fig. 1 (a) to (d) show examples of an apparatus for sensing features of an object;

[0065] Fig. 2 (a) to (b) show further examples of an apparatus for sensing features of an object;

[0066] Fig. 3 (a) to (b) show more examples of an apparatus for sensing features of an object;

[0067] Fig. 4 (a) to (c) show some more examples of an apparatus for sensing features of an object, wherein only the lower part of the sensor is shown;

[0068] Fig. 5 (a) and (b) show further examples of an apparatus for sensing features of an object;

[0069] Fig. 6 (a) to (c) show examples of temporal courses of a perturbation and a resulting physiological effect;

[0070] Fig. 7 (a) to (d) show further examples of temporal courses of a perturbation;

[0071] Fig. 8 (a) and (b) show diagrams illustrating an example of a synchronization of the perturbation pulses to an external physiological signal; and

[0072] Fig. 9 (a) shows a flowchart illustrating an example of a static perturbation loop, and (b) shows a flowchart illustrating an example of a perturbation loop which is executed in an adaptive fashion.

[0073] Figure 1 (a) shows a schematic cross-sectional view of an example of an apparatus for sensing features of an object 1, e.g. biological tissue of a subject or a plant or fruit. Theapparatus comprises a sensor 2 having an irradiation device 5 which is configured to irradiate a region of interest of the object 1 with electromagnetic radiation 6, and a detection device 7 which is configured to detect a response signal emanating from the region of interest in response to the irradiation with the electromagnetic radiation 6. Preferably, the irradiation device 5 is configured to irradiate the region of interest with time-varying, in particular pulsed, electromagnetic radiation to excite ultrasound waves, also referred to as optoacoustic waves, in the region of interest, and the detection device 7 is configured to detect the optoacoustic waves emanating from the region of interest.

[0074] The sensor 2 further comprises a housing 3 having a contact wall 3a which is configured to be brought into contact with the object 1. Optionally, one or more spacers 3b may be provided, preferably at the outer side of the contact wall 3a, to create a space or spaces between a surface 1a of the object 1 and the contact wall 3a when the sensor 2 is placed onto the object 1. Preferably, the contact wall 3a is provided with one or more openings 3c to allow a gas flow and / or pressure equalization between the interior of the housing 3 and the surface 1a of the object 1 and / or space(s), which is (are) preferably formed by means of the spacers 3b, between the surface 1a and the contact wall 3a.

[0075] A pressure controller 4, such as an air or gas pump, is coupled to the housing 3 and configured to increase and / or decrease a gas pressure in the interior of the housing 3 and, due to the openings 3c provided in the contact wall 3a, at or above the region of interest of the object 1 , in particular in the space(s) between the surface 1 a and the contact wall 3a. The pressure controller 4, which is an example of a perturbation device in accordance with the present disclosure, is configured to apply a mechanical perturbation, in particular a temporary mechanical perturbation, to the region of interest of the object 1 by temporarily increasing and / or decreasing the gas pressure prevailing in the housing 3 and at the region of interest, in particular in the space(s) between the surface 1a and the contact wall 3a.

[0076] A processor 8 is configured to control the irradiation device 5 to irradiate the region of interest with the electromagnetic radiation 6 while the perturbation, in particular a pressure increase and / or decrease, is being and / or after the perturbation has been applied, and to derive, on the basis of the response signal detected in response to the irradiation, information characterizing at least one feature of the object 1, in particular with respect to an effect of the perturbation on the at least one feature of the object 1.For example, the at least one feature may be a concentration of a molecule of interest in the object 1, such as glucose, cortisol, troponin, lactate or fructose in tissue and / or a lipid such as omega-3 and omega-6 lipids, proteins and / or carbohydrates and / or water in food, plants or tissue. Alternatively or additionally, the at least one feature may be a density and / or functionality of at least one structural component of the object 1 , e.g. a functionality such as a dilatation and / or constriction behavior of a microvasculature in the object 1.

[0077] The example described above with reference to Figure 1 (a) is only one preferred embodiment of an apparatus and a corresponding method for sensing features of an object according to the present disclosure. It is noted, however, that the general approach of the present disclosure relates to a kind of new sensor class for sensing features of an object which covers a variety of different embodiments, in particular in terms of applying a perturbation and exciting and / or detecting a response signal. This is further described below and illustrated using other or alternative examples depicted in the figures.

[0078] Generally, a sensor, such as sensor 2 shown in Figure 1 (a), can be employed to retrieve at least one measurement from an object 1 of interest, for example the human skin, wherein the measurement can be a single measurement at a single time point, a single measurement at multiple time points, or multiple measurements at multiple time points and / or multiple spatial points. Although the above and following examples describe preferred aspects of the present disclosure with respect to a single measurement in space and time, the above and following description applies equally to any multiple of measurements through time and / or space.

[0079] Generally, such a single measurement can be simply obtained by placing a sensor, such as sensor 2 shown in Figure 1 (a), on the object 1 of interest, for example the human skin. This placement, however, can take many forms, for example it can use a machinery which not only creates a certain pressure or pressure variation to the object 1 of interest, but also and / or alternatively modifies its temperature, administers drugs and chemicals and perturbs the object 1 of interest in a controlled way. The control method can have critical effects on the result of the measurement. Moreover, by performing single measurements over time while that perturbation is applied on the object 1 of interest, this can reveal even more critical parameters about the object 1 of interest or a condition acting upon it.Generally, an apparatus according to the general approach of the present disclosure preferably comprises a sensor, such as sensor 2 shown in Figure 1 (a), also referred to as measurement device, typically comprising at least one energy emitter, such as irradiation device 5 shown in Figure 1 (a), at least one energy detector, such as detection device 7 shown in Figure 1 (a), a certain geometrical arrangement that controls the placement of the emitter 5, detector 7 and object 1 of interest to each other and a perturbation unit, such as pressure controller 4 shown in Figure 1 (a), which modifies a parameter of the object 1 of interest. The sensor 2 is connected to a controller or processing unit, such as processor 8 shown in Figure 1 (a), that controls the perturbation, data collection (response signal detection) and data processing (response signal processing).

[0080] The emitted energy 6 may be different than the collected energy, for example in the case of optoacoustic or fluorescence measurements, where the emitted energy 6 is electromagnetic radiation, while the detected energy of the response signal corresponds to (opto-)acoustic waves or electromagnetic fluorescence radiation, respectively. Alternatively, these energies may also be identical, for example in the case of Raman scattering and associated methods such as CARS and SRS.

[0081] In preferred examples, the perturbation unit 4 is a device which controls the pressure of the air in a volume adjacent to and / or above the region of interest of the object 1 , as exemplarily described above with reference to Figure 1 (a), where a sensor 2 is placed, e.g., on human skin 1a, and a pressure controller 4 reduces the pressure within a housing 3 that is in contact with the object 1 of interest. The low pressure (hypo pressure) forces the object 1 of interest’s surface 1a to deform and reach a specific point on and / or relative to the sensor 2, also referred to as central point. In the example of Figure 1 (a), the central point is located at a central opening 3c and / or window provided in the contact wall 3a that allows illumination of the object 1 of interest with light 6 of transient energy, typically 0.01 - 100 nanosecond range light pulses, to create an optoacoustic signal in the object 1 of interest. Preferably, the contact wall 3a is designed such that the central point and / or central opening 3c is surrounded by an area containing one or more ultrasound transducer elements or detectors 7, which are preferably provided in and / or close to the contact wall 3a. Due to the negative (hypo) pressure, the object 1 of interest’s surface 1a comes into contact with the ultrasound detectors 7 which record the optoacoustic signals excited in the object 1 of interest. Further openings 3c in the contact wall 3a enable an efficient generation of hypo-pressure throughout the volume adjacent to and / or above the object 1 ofinterest’s surface 1a, for efficient deformation of the object 1 of interest’s surface 1a and enabling good contact with the ultrasound detectors 7, as indicated in Figurel (a).

[0082] Figure 1 (b) shows a variant of the preferred example shown in Figure 1 (a). The contact wall 3a of the housing 3 has only a central opening 3c through which the electromagnetic radiation 6 can pass and to which the surface 1a of the object 1 of interest is attracted when the pressure controller 4 generates a negative pressure in the volume. Otherwise, the above description with reference to Figure 1 (a) applies accordingly.

[0083] Figure 1 (c) shows another variant, where detectors 7 are placed on springs 7a, preferably leaf springs, which are fixed on spacers 3b provided at the lower edge of the housing 3 so that when the surface 1a of the object 1 of interest is attracted to the housing 3 due to a negative or lower pressure generated by pressure controller 4, the object 1 of interest’s surface 1a comes in contact with the detectors 7 which puts them under extra tension due to the spring tension. In this manner, an excellent contact between the detectors 7 and the object 1 of interest’s surface 1a is ensured. Optionally, tension measurement, spring displacement measurements (such as with distance sensors or optical imaging techniques or optical distance sensors) or any other measurement that monitors an interaction between detectors 7, springs 7a and / or the object 1 of interest’s surface 1a can be used to determine the exact position of the object 1 of interest’s surface 1a. In this example, the sensor 2 contacts the surface 1a via the detectors 7 and the spacers 3b provided at the edge of the housing 3, and the electromagnetic radiation 6 passes a central opening 3c which is provided between and / or formed by the detectors 7. Otherwise, the above description with reference to Figures 1 (a) and (b) applies accordingly.

[0084] Figure 1 (d) shows yet another variant, where detectors 7’ are arranged to establish a trans-illumination mode, i.e. enclosing the object 1 between irradiation device 5 and at least one detector for 7’, either together with detectors 7 placed on the same side of the irradiation device 5 (i.e. in epi-illumination mode) or without them. A sensor 2 that establishes a contact of the two object 1 of interest’s surfacesla, one in contact with the housing 3 and the other in contact with the transillumination detector 7’ can be a stationary frame or enclosure or a device that can move the transillumination detector 7’ in relation to the housing 3, thus determining their relative distance and pressure applied to the object 1 of interest. Otherwise, the above description with reference to Figures 1 (a) to (c) applies accordingly.In other variants, one or more detectors 7 are made of material that is transparent to the energy 6 emitted by the source 5, therefore the transmission occurs through the detectors) 7, as exemplified for one detector 7 in Figure 2 (a). Otherwise, the above description with reference to Figures 1 (a) to (d) applies accordingly.

[0085] According to another variant, two or more sources 5 can be employed and placed around one or more ultrasound detectors, as exemplified for one detector 7 in Figure 2 (b). Otherwise, the above description with reference to Figures 1 (a) and (d) applies accordingly.

[0086] Preferably, a pressure sensor 9 can be provided, e.g. in the interior of the housing 3 and / or close to any of the detectors 7, which is configured to sense the pressure within the housing 3 and / or to give real-time feedback to the pressure controller 4 and / or establish a feedback loop for accurate stabilization and control of the pressure in the housing 3 or the pressure applied in trans-illumination (cf. Figure 1 (d)), respectively.

[0087] Preferably, at the interface of the sensor 2 to the object 1 of interest’s surface 1a (e.g. at the exterior of the contact wall 3a) special elastic, rubber or other materials may be provided to ensure that no air from the outside will leak into the hypo-pressurized interior of the housing 3.

[0088] Preferably, the response signal, e.g. optoacoustic waves, can be obtained or detected at one or multiple time points throughout (during) and / or after the pressure change, e.g. during and / or after a hypo-pressure is established. This design also allows measurements over time and over different pressure levels.

[0089] The examples described above have multiple advantages. For example, the surface 1a of the object 1 of interest can be reliably placed at a very specific and / or desired point in space, in relation to the energy emitter 5 and detectors 7. Further, the sensor 2 is reliably stabilized in relation to the surface of the object 1 of interest. Therefore, motion artifacts may be reduced. Moreover, measurements under a single or multiple specific pressure point(s) may be performed which can be used to study the effects of pressure or pressure changes on the object 1 of interest or, critically, perform measurements under specific altered forms of object 1 of interest status, for example by altering the density of one or multiple properties measured, due to the hypo-pressure condition.The measurement approach described above can be generalized in that cycles of pressure (hypo and hyper) can be established and the property investigated can be studied under these changing conditions. For example, aspects of microvasculature functionality can be measured due to a pressure perturbation, by conducting a measurement through the perturbation and resolving how the parameter of interest changes, e.g. how vessels dilate and constrict due to the perturbation. Such measurements are expected to contain information that can separate health from disease, for example cardiovascular disease, and be used for various medical purposes such as early disease detection or monitoring progression and effect of interventions. Likewise, when monitoring food, such perturbations can reveal aspects of water content, ripeness, quality etc. Such perturbation can also help concentrate a metabolite of interest under the point of energy deposition and measurement, thus improving the sensitivity, specificity and accuracy of the measurement.

[0090] Generally, the emitted energy 6 and the detected response signal(s) can be of various forms as exemplarily described in the following.

[0091] Preferably, the emitted energy 6 is mid-infrared light, tuned at wavenumbers where a metabolite or other molecule of interest preferentially absorbs. Preferably, the light can be focused on or inside the object 1 of interest or it can be illuminated as a broad beam, collimated beam or diverging beam.

[0092] Preferably, the sensor 2 can be provided with a scan mechanism, such as one or more stepper motors or one or more galvanometers with attached mirrors and / or lenses in order to scan the light onto the object 1 of interest’s surface 1a.

[0093] Preferably, the detector(s) 7 can be ultrasound detector(s) for optoacoustic measurements, in particular when the energy of the emitted light is transient, i.e. it changes over time, to excite optoacoustic or ultrasound waves. For example, the ultrasound detectors 7 can be flat detectors or use acoustic lensing to also detect from focal areas in the object 1 of interest. If light scanning is used, then the data (sponsor signal(s)) collected can be tomographically processed and / or reconstructed to yield images, as it is common in the field of optoacoustic mesoscopy (see Omar M. et al., Nature Biomedical EngineeringPreferably, in the case of optoacoustic sensing, time-gating techniques can be employed to detect signals from different depths. Depth gating techniques reading from specific volumes in tissues (see, e.g., Uluc et al., Nature Metabolism 2024) help to retrieve signals from deeper in tissue, i.e. under the object 1 of interest’s surface 1a, gaining access to particular object 1 of interest’s compartments where the property of interest is abundant or concentrated.

[0094] Alternatively, the emitted energy 6 is light and the detectors 7 are optical detectors, such as Raman scattering detecting elements using appropriate filters or other detection technique. While time-gating is not possible in this case, focusing the light at different depths inside the tissue may impart certain depth selectivity.

[0095] Preferably, a depth-dependent focusing can be achieved by physically moving the emitter 5 in relation to the central point, which is preferably achieved by modifying the pressure in the housing 3 resulting in an adjustment of the object 1 of interest’s surface 1a in relation to the central point, or by any other method such as repositioning the central point itself by moving the detectors 7 and / or the surface containing the detectors 7. It is noted that such operations also depend on the physical size of the central opening 3c at or around the central point, especially since a large central opening 3c allows for more flexibility in regard to moving the object 1 of interest’s surface using pressure modulation.

[0096] Preferably, the exact location of the object 1 of interest’s surface 1a, for example in relation to a focal point established by the emitter 5 and / or the detector(s) 7, is determined. Preferably, distance sensors 11 are provided, preferably in the housing 3, to sense and / or measure the distance (e.g. between the object 1 of interest’s surface 1a and / or focal point and the emitter 5) through the central point or opening 3c, as indicated in Figures 3 (a) and (b) where distance sensors 11 are provided at the irradiation unit 5.

[0097] When using optoacoustic measurements, the surface 1a can be detected in time, as the first time-point whereby a signal (i.e. acoustic waves) of high intensity arrives. Filtering operations, for example high-pass filtering of the optoacoustic signal can be helpful to increase the accuracy of determining that time point, indicating the exact location of theobject 1 of interest’s surface 1a in relation to the detector(s) 7. It is possible that an additional ultrasound detector can be employed in the place of the distance sensor(s) 11 in Figures 3 (a) and (b).

[0098] It is noted that the preferred aspects described above can, alternatively or additionally, be implemented in the examples shown in Figures 1 and 2.

[0099] It is further noted that the design of the preferred examples or variants shown in Figures 1 to 3 is to be taken just as a general guideline which can operate in any dimensions and angles. For example, the emitter 5 could be titled or placed next to a single or few ultrasound elements 7 or optical detectors, as exemplified on Figure 2 (b)

[0100] In another preferred example, the perturbation mechanism and device does not relate to pressure but to temperature, i.e. the temperature of the object 1 of interest or object 1 of interest’s surface 1a is modified. As exemplarily shown in Figure 3 (b), a temperature controller 4’ and / or thermal element 4” and / or an infrared source or any other heating element is provided, preferably in and / or coupled to the housing 3, to modify or modulate the temperature of the surface 1a and / or the object 1 of interest.

[0101] Preferably, such a measurement is performed similarly to measurements in conjunction with pressure variations (as described further above) to examine functional features of the object 1 of interest. For example, in the case of skin, a temperature variation over time modulates the vasodilation of skin microvasculature and can reveal functional alterations on such vasodilation patterns as they associate with micro-endothelial dysfunction and other such alterations.

[0102] Preferably, one or more thermometers 9’ can be provided, preferably in or on the housing 3, to monitor the temperature and offer stability control via feedback loops. When the sensor 2 is used for optoacoustic detection, variations of the optoacoustic signal also depend on temperature variations and can be employed to monitor it. Therefore, the housing 3 could incorporate a control absorber to act as a reference in relation to temperature or other changes. The control absorber can be placed in proximity to the central point and / or central opening 3c of the housing 3, so that these signals can be monitored by any of the detectors 7 shown in the examples of Figures 1 to 3.It is noted that perturbations can be further induced by other forms of impact on the object 1 or by chemicals and drugs. In addition, combinations of multiple perturbation methods, such as pressure and temperature, are possible and can allow the collection of broader information about the object 1 of interest compared to stand-alone perturbations and other sensors.

[0103] Moreover, combinations of the above perturbations could lead to modulation patterns with enhanced information content. For example, pressure modulation under different temperatures, or temperature modulation for one given pressure. Such perturbations are expected to concentrate better moieties of interest in the central point, for example metabolites, for example glucose, cortisol, troponin or lactate or fructose and plant of food-related parameters. Such perturbations are also expected to better modulate vasodilatory or vasoconstrictive responses, perfusion and total hemoglobin content, oxygenation possibly spectrally resolved by resolving oxy- and deoxy-hemoglobin in tissues and other functional responses. While single perturbations could also reveal these parameters, combinations or control of one parameter (for example temperature) while another perturbation is ongoing (for example pressure) may improve the accuracy and reproducibility of the measurement, i.e. enhance quality of operation and reduce variability.

[0104] For example, the sensor 2 can also be applied to foods to detect omega-3 and omega-6 lipids in foods, plants or tissues. Other lipids, proteins or carbohydrates can be resolved by spectral methods, for example illumination at two or more wavenumbers in the mid-IR. By tuning the illumination wavenumber(s) around an absorption peak of a molecule of interest and possibly around wavenumbers that represent background, optoacoustic detection of the molecule of interest is possible by subtraction or unmixing methods and / or by time-gating as described above.

[0105] For example, the sensor 2 can be applied to tissue in-vivo to detect circulating metabolites or other moieties applying spectral and / or time-gating techniques, wherein the latter are preferably employed to reject non-specific contributions from the surface and possibly read from depths rich in vasculature, better representing measurements in-blood. Besides glucose, troponin and lactate could be detected using their particular spectral absorption signature, in particular in the so-called fingerprint region.Preferably, the respective controller 4, 4’ in the sensor 2 could include any method that applies pressure or enforces a vacuum (and states in between), using air pumps, moving pistons or membranes and / or changes the temperature of the air or other coupling medium gas or fluid etc. Since temperature changes can be used to change the volume and therefore the pressure of a gas, temperature could be used both to control pressure and temperature also in terms of the perturbation applied.

[0106] Preferably, in the implementation shown in Figure 1 (a), a focused irradiation device 5 is provided, the focus point(s) of which being placed preferably inside the object 1 of interest, i.e. not on but under the object 1 of interest’s surface 1a.

[0107] Preferably, a precise placement of the focal point(s) can be achieved by distance sensors) 11 (see Figures 3(a) and (b)) and / or an optical unit (e.g. a moving, e.g rotating, mirror) and / or a mechanical unit (e.g. stage for a lateral and / or relative movement between sensor 2 and object 1) that moves the irradiation device 5 in relation to the object 1 of interest’s surface 1a. However, a different approach could use a collimated beam or a beam with a long focal length.

[0108] As illustrated in Figures 4 (a) to (c), which only show the lower part of the sensor 2, instead of a central opening 3c (see Figures 1 and 3) a rigid interface, for example a glass window 12 (see Figure 4 (a)) or the irradiation device(s) 5 (see Figures 4 (b) and (c)), can be provided in or at the contact wall 3a of the housing 3 so that despite the deformation of the surface 1a due to the reduced pressure in the housing 3, the surface 1a always lays flat against and / or on the sensor (i.e. against and / or on the glass window 12 or the front of the irradiation device(s) 5, respectively) and at a specific distance from the irradiation device 5. This enables a particularly precise knowledge of the position of the surface 1a and placement of the focus point(s) of the focused beam 6. Preferably, the window 12 itself can have micro-openings to allow the reduced pressure to reach the object 1 of interest’s surface 1a. Alternatively or additionally, openings 3c may be provided between the window 12 and the detectors 7 and / or at other positions in the contact wall 3a as indicated in Figures 4 (a) to (c). Depending on the electromagnetic energy 6 emitted by the irradiation device 5, the window 12 may be of different materials and designs, wherein glass may be appropriate for light in the visible or near-infrared spectral range. Otherwise, the above description with reference to Figures 1 to 3 applies accordingly to Figures 4 (a) to (c).Figures 5 (a) and (b) show schematic cross-sectional views of further examples of an apparatus for sensing features of an object 1. In distinction to the examples described above, in these variants the contact area of the sensor 2 is kept small in relation to its active measurement area. Preferably, the sensor’s 2 touching area for the object 1 under investigation is minimized to a sufficient area to ensure sufficient measurements, but limited to not influence the tissue 1 under test outside of the measurement area. This enhanced “pointiness” and the avoidance of contact with the skin 1a adjacent to the measurement site is particularly advantageous, as it helps to prevent local pressure that could alter perfusion or displace blood, minimizes thermal influence, and ensures that the skin 1a remains uncovered, thereby preventing the accumulation of sweat and avoiding the induction of perspiration due to occlusion. Otherwise, the above description with reference to Figures 1 to 4 applies accordingly to Figures 5 (a) and (b).

[0109] Figures 6 (a) to (c) show examples of temporal courses of a perturbation P (dashed line) and a respectively resulting physiological effect E (solid line) in the investigated object. The respective magnitudes of the perturbation P and the resulting physiological effect capital E are given in arbitrary units [AU].

[0110] According to the example shown in Figure 6 (a), a step-like or “on-off’ perturbation P, such as a positive or suction and / or negative pressure or temperature change, is applied to a region of interest of an investigated object. A resulting physiological effect E, which is manifested in a detected response signal, e.g. an optoacoustic or optical response of the object when excited and / or irradiated with electromagnetic energy, starts at the end of the perturbation P and increases subsequently.

[0111] According to the example shown in Figure 6 (b), a perturbation P, such as a positive or negative pressure and / or suction or temperature change, applied to the region of interest of the object is temporarily switched off, whereupon the resulting physiological effect E manifested in the detected response signal starts shortly after the switch-off of the perturbation P, then increases to a maximum and then falls back to its initial magnitude.

[0112] According to the example shown in Figure 6 (c), a perturbation P, such as a positive or negative pressure and / or suction or temperature change, applied to the region of interest of the object has periodic temporal course in the shape of a square wave, i.e. a periodic“on-off” switch, whereupon the resulting physiological effect E manifested in the detected response signal shows an increase after the switch-off of the perturbation P and a subsequent decrease after the switch-on of the perturbation P.

[0113] Further, Figures 6 (a) to (c) exemplarily illustrate how the detected response signals reflecting the physiological effect E of the perturbation P can be evaluated by the processor. Apparently, after perturbation step functions (or perturbation peaks), one or more of the following metrics can be assessed: (a) the rate of change over time of the detected response signal (measured value or set of measured values); (b) the time to reach a maximum (or minimum) of the detected response signal (measured value or set of measured values); (c) the time-integral of the detected response signal (measured value or set of measured values).

[0114] Preferably, the measured property can be one, or a combination, of the aforementioned parameters (metrics) after the change(s) of the perturbation magnitude, i.e. (i) the rate of change overtime of the physiological property, (ii) the time to maximum of the physiological property, and / or (iii) the time-integral of the physiological effect after the perturbation.

[0115] Preferably, in particular for real-time measurement deviations, at least one parameter of the modulation function can be adjusted, such as repetition-rate of the cycle, slopes of ramping functions, and / or the absolute amplitude of the modulation function.

[0116] Preferably, the processor 8 (as exemplarily shown in Figs. 1 to 3) is configured to derive at least one of the mentioned metrics from the detected response signal(s) to derive information characterizing at least one feature of the object, in particular with respect to an effect of the perturbation P on the at least one feature of the object.

[0117] In the examples described above, for the sake of simplicity, the perturbation magnitude is referred to in binary terms (“on” and “off’). However, using a continuous control value (setpoint) for the magnitude of the perturbation P may be an advantageous alternative. Generally, any temporal course of the perturbation magnitude may be preferred and / or suitable.Figures 7 (a) to (d) show further examples of temporal courses of a perturbation P (perturbation changing functions).

[0118] Figure 7 (a) shows a repetitive negative step function of the perturbation (e.g., short durations of negative pressure and / or suction). Figure 7 (b) illustrates the inverted situation, i.e. short positive step function pulses (e.g., constant negative pressure and / or suction with brief returns to ambient pressure).

[0119] Figure 7 (c) exemplarily shows an application of arbitrary decay functions for modulating the perturbation magnitude (e.g., a step to a certain value followed by exponential decay).

[0120] Figure 7 (d) shows an arbitrary static and piecewise-differentiable function of the perturbation magnitude (e.g., ramping up and down with different slopes between two setpoints).

[0121] Figures 8 (a) and (b) show diagrams illustrating an example of a synchronization of the perturbation pulses P to an external physiological signal EP. In the shown example, the perturbation P is synchronized to every second rising edge of an ECG rhythm EP (the “R-wave,” as introduced by Einthoven).

[0122] Skipping parts of the external trigger signal (e.g., triggering only on every second R-wave) is advantageous, as it allows for internal baseline correction, for example, by normalizing measurement values (the response signal(s)) to conditions that would have occurred without the perturbation.

[0123] Preferably, the described perturbation magnitude modulations can be performed either in a static fashion or adaptively, depending on physiological feedback that adjusts the parameters based on real-time measurements.

[0124] Figure 9a shows a flowchart illustrating an example of a static perturbation loop with two setpoints. After adjusting the perturbation to setpoint 1, a response signal is acquired and stored (“Data 1 ”) for that setpoint. The apparatus, in particular the processor 8, then adjusts the perturbation to setpoint 2, performs a corresponding measurement of another response signal, and stores the resulting data (“Data 2”). Preferably, in the static perturbationloop, the perturbation setpoints and the time constants (i.e. , the duration each step is held) remain fixed and do not depend on the measured response signal or corresponding data.

[0125] Figure 9b shows a flowchart illustrating an example of another implementation in which the perturbation loop is executed in an adaptive fashion. For example, setpoint 1 is ad-justed, followed by a first measurement of a corresponding response signal (“Acquire Signal 1”). This measurement is repeated until a predefined condition (illustrated by “?”) is met. For example, a predefined condition can be whether a measured value (i.e. a value of the acquired response signal) or set of values (i.e. a set of values of acquired response signals) exceeds (a) certain threshold(s). Once the condition is fulfilled, the apparatus, in particular the processor 8, adjusts to a second perturbation setpoint and repeats the measurement process of a corresponding response signal (“Acquire Signal 2”) until a next condition (“?”) is satisfied.

Claims

Patent Claims1. An apparatus for sensing features of an object (1), in particular biological tissue, the apparatus comprising- a perturbation device (4, 4’, 4”) configured to apply a perturbation, in particular a temporary perturbation, to a region of interest of the object (1),- an irradiation device (5) configured to irradiate the region of interest, to which the perturbation is being and / or has been applied, with electromagnetic radiation (6), and- a detection device (7’, 7’) configured to detect a response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation (6), and- a processor (8) configured to derive, on the basis of the response signal, information characterizing at least one feature of the object (1).

2. The apparatus according to claim 1 , wherein the perturbation device (4, 4’, 4”) is configured to apply a mechanical perturbation to the region of interest by applying a suction to the region of interest or applying a negative pressure to the region of interest or reducing the pressure at or in the region of interest below ambient pressure, and the processor (8) is configured to derive, on the basis of the detected response signal emanating from the region of interest, to which the suction or negative pressure or pressure below ambient pressure is being and / or has been applied, information characterizing at least one feature of the object (1).

3. The apparatus according to claim 2, wherein the perturbation device (4, 4’, 4”) comprises at least one of the following:- a fluid pump(4), in particular an air pump such as a vacuum pump or a water pump, configured to decrease a fluid pressure, in particular a gas or liquid pressure, prevailing in a volume adjacent to the region of interest, and / or- at least one movable piston and / or diaphragm and / or peristaltic pump configured to increase a volume adjacent to the region of interest, resulting in a decrease in fluid pressure, in particular gas or liquid pressure, prevailing in the volume, and / or - a temperature controller (4’) configured to control, in particular to decrease, thetemperature of a fluid, such as air and / or a gaseous and / or liquid coupling medium, such as water and / or ultrasound gel, contained in a volume adjacent to the region of interest, thereby decreasing the fluid pressure, in particular gas or liquid pressure, prevailing in the volume.

4. The apparatus according to claim 2 or 3, wherein the perturbation device (4’, 4”) is further configured to apply a thermal perturbation to the region of interest, in particular by modifying and / or modulating the temperature of the region of interest, and the processor (8) is configured to derive, on the basis of the detected response signal emanating from the region of interest, to which i) the suction or negative pressure or pressure below ambient pressure and ii) the thermal perturbation are being and / or have been applied, information characterizing at least one feature of the object (1).

5. The apparatus according to claim 4, wherein the perturbation device (4’, 4”) comprises at least one of the following:- a thermoelectric element (4”), in particular a thermocouple or Peltier element, configured to be brought into contact with the region of interest to increase and / or decrease the temperature of the region of interest, and / or- a radiation source configured to irradiate the region of interest with electromagnetic radiation, in particular infrared (IR) and / or ultraviolet (UV)radiation and / or visible light, to increase the temperature of the region of interest, and / or- an ultrasound wave source configured to couple high intensity focused ultrasound waves (HIFU) into the region of interest to generate heat at a focal zone of the focused ultrasound waves.

6. The apparatus according to any one of the preceding claims, wherein the perturbation device is further configured to apply the perturbation to the region of interest by applying and / or administering at least one chemical or drug, in particular a substance configured to increase the blood volume in the object, to the region of interest.

7. The apparatus according to any one of the preceding claims, wherein the irradiation device (5) comprises a radiation source configured to irradiate the region ofinterest, to which the perturbation is being and / or has been applied, with time-varying, in particular pulsed, electromagnetic radiation (6), and the detection device (7) comprises at least one ultrasound transducer configured to detect, as the response signal, ultrasound waves emanating from the region of interest in response to irradiating the region of interest with the time-varying, in particular pulsed, electromagnetic radiation (6).

8. The apparatus according to any one of the preceding claims, wherein the detection device (7) comprises at least one radiation detector configured to detect, as the response signal, electromagnetic radiation, in particular reflected and / or scattered, preferably Raman scattered, and / or fluorescent radiation, emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation (6).

9. The apparatus according to any one of the preceding claims, wherein the perturbation device (4, 4’, 4”) is configured to apply the perturbation repeatedly, in particular periodically and / or cyclically, to the region of interest of the object (1), and the detection device (7) is configured to detect the response signal emanating from the region of interest in response to irradiating the region of interest, to which the perturbation is being and / or has been applied repeatedly, with the electromagnetic radiation (6).

10. The apparatus according to any one of the preceding claims, wherein the processor (8) is configured to receive an external signal (EP) characterizing at least one naturally occurring internal perturbation of the region of interest, in particular a cardiac or respiratory cycle of the object, and- to control the perturbation device (4, 4’, 4”) such that the application of the negative pressure and / or pressure below ambient pressure and / or the thermal perturbation to the region of interest is controlled and / or synchronized and / or gated and / or triggered by the external signal (EP) and / or by the at least one naturally occurring internal perturbation of the object, and / or- to control the irradiation device and / or the detection device such that the detection of the response signal(s) emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation is (are) con-trolled and / or synchronized and / or gated and / or triggered by the external signal (EP) and / or by the at least one naturally occurring internal perturbation of the object.

11. The apparatus according to any one of the preceding claims, wherein the processor (8) is configured to derive, on the basis of the response signal emanating from the region of interest, to which the negative pressure and / or pressure below ambient pressure and / or the thermal perturbation and / or the at least one naturally occurring internal perturbation, is being and / or has been applied, at least one of the following information characterizing one or more features of the object:- a presence and / or concentration of at least one molecule of interest in the object (1), in particular at least one metabolite such as glucose, cortisol, troponin, lactate or fructose in tissue and / or at least one lipid such as omega-3 and omega- 6 lipids, proteins and / or carbohydrates and / or water in food, plants or tissue, and / or- a presence, density and / or functionality of at least one structural component of the object (1), in particular a functionality such as a dilatation and / or constriction behavior of a microvasculature in the object in response to the perturbation, and / or- a spectral appearance of the object (1), and / or- a density of the object (1), and / or- a position of a surface (1a) of the object (1) relative to the irradiation device (5) and / or detection device (7).

12. The apparatus according to claim 11, wherein the processor (8) is configured to derive, from the information characterizing one or more features of the object (1), - if the object (1) is an individual, a diagnostic information characterizing a state of health of the individual, and / or,- if the object (1) is food, such as a plant and / or fruit, information characterizing at least one of a water content, ripeness and / or quality of the food.

13. The apparatus according to any one of the preceding claims, wherein the detection device (7) is configured to detect the response signal emanating from the region of interest over time, and wherein the processor (8) is configured to select a portion of the response signal, which has been detected during a specified timegate corresponding to a volume or layer in the object (1), and to derive the information characterizing at least one feature of the object (1) on the basis of the selected portion of the response signal.

14. The apparatus according to any one of the preceding claims, wherein the detection device (7) is configured to detect the response signal (E) emanating from the region of interest over time, in particular after the negative pressure and / or pressure below ambient pressure and / or the thermal perturbation and / or the internal perturbation has or have been applied, and wherein the processor (8) is configured to derive the information characterizing at least one feature of the object (1) based on at least one of the following:- a rate of change characterizing a ratio of a change of the response signal (E) per unit of time ([s]), and / or- a time to maximum characterizing a period of time it takes for the response signal (E) starting from an initial signal (onset) to reach its maximum, and / or- a time integral of the response signal (E), in particular over a period of time between an initial signal (onset) and a maximum of the response signal (E).

15. The apparatus according to any one of the preceding claims, wherein the processor (8) is further configureda) to adapt at least one property of the perturbation, in particular a speed and / or a frequency and / or an amplitude of the perturbation, based on the detected response signal and / or on the information derived from the detected response signal, to obtain an adapted perturbation,b) to control the perturbation device (4, 4’, 4”) to apply the adapted perturbation to the region of interest of the object (1),c) to control the irradiation device (5) to irradiate the region of interest, to which the adapted perturbation is being and / or has been applied, with the electromagnetic radiation (6), and to control the detection device (7) to detect an adapted response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation (6), wherein, optionally, the steps a) to c) are repeated one or more times (closed-loop feedback mechanism), and- to derive, on the basis of the adapted response signal, the information characterizing the at least one feature of the object (1).

16. A method for sensing features of an object (1), in particular biological tissue, the method comprising the following steps:- receiving and / or accessing a response signal which has been detected in response to irradiating a region of interest of the object (1), to which a perturbation, in particular a temporary perturbation, is being and / or has been applied, with electromagnetic radiation (6), and- deriving, on the basis of the response signal, information characterizing at least one feature of the object (1).

17. A computer program product comprising instructions causing the processor (8) of the apparatus according to any one of the claims 1 to 15 to execute the steps of - controlling the perturbation device (4, 4’, 4”) to apply a perturbation, in particular a temporary perturbation, to a region of interest of the object (1),- controlling the irradiation device (5) to irradiate the region of interest, to which the perturbation is being and / or has been applied, with electromagnetic radiation (6),- controlling the detection device (7) to detect a response signal emanating from the region of interest in response to irradiating the region of interest with the electromagnetic radiation (6), and- deriving, on the basis of the response signal, information characterizing at least one feature of the object (1).

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