WO2017028892A1

WO2017028892A1 - A technique for determining a physiological state of a test subject

Info

Publication number: WO2017028892A1
Application number: PCT/EP2015/068834
Authority: WO
Inventors: Maximilian Fleischer; Andreas Kappel; Erhard Magori; Roland Pohle; Kerstin Wiesner; Oliver von Sicard
Original assignee: Siemens Aktiengesellschaft
Priority date: 2015-08-17
Filing date: 2015-08-17
Publication date: 2017-02-23
Also published as: EP3338087A1

Abstract

A method and a device for determining a physiological state of a test subject is presented. In the method, a first VOC pattern is determined from a first test medium and a second VOC pattern is determined from a second test medium. The first VOC pattern has a first group of VOCs and includes one or more VOCs detected in the first test medium and their respective concentrations. The second VOC pattern has a second group of VOCs and includes one or more VOCs detected in the second test medium and their respective concentrations. Subsequently, the first and the second VOC patterns are combined to obtain a VOCome pattern. Finally, the VOCome pattern is compared to a reference pattern. The reference pattern comprises a collection of different VOCs and concentrations of each of the different VOCs and represents a predicted known physiological state of the test subject.

Description

A technique for determining a physiological state of a test subj ect

The present technique is related to determining a

physiological state of a test subject.

Volatile organic compounds, hereinafter referred to as VOCs are excreted out of a body of an organism e.g. human body i.e. a test subject, through different ways for example in exhaled breath, perspirations, urine, etc. and are

representative of different physiological states of the body. For example, physiological condition of kidney may be

physiologically normal or physiologically abnormal and may be studied by studying the VOCs excreted in the urine of the test subject. Similarly, by studying VOCs in ethanol or acetone analyzing breath test, an amount of alcohol blood level or an amount of carbohydrate depletion in the body of the test subject may be studied.

The knowledge of physiological condition or physiological state of the test subject is important for determination of different pathological conditions as well as for therapy monitoring and guidance. However, the presently known assays based on VOC are dependent on detection of specific VOCs from a given source of sample obtained from the test subject, for example in a breath analysis test only the breath of the test subject in analyzed for VOCs. This has a disadvantage of not being able to determine a physiological state or condition that may not be manifested by VOCs of that given sample but may be manifested by VOCs of another sample taken from a different source of the test subject. Thus, scopes of the VOC assays known presently are limited.

Hence a technique is needed to assess a physiological state of a test subject or a change in a physiological state of the test subject. Monitoring physiological states of the test subject may be helpful to detect malfunctioning or loss of any physiological functions, which may in turn trigger delivery of early treatment and life style changes.

Advantageously, the technique of monitoring or determining the physiological state should be non-invasive, i.e.

requiring no blood draw or invasive sample collection, in order to promote wide application and to include test

subjects who are opposed or unwilling to invasive techniques. Thus, the object of the present technique is to provide a simple technique for determining a physiological state of a test subject. The technique is desired to be noninvasive.

The above objects are achieved by a method for determining a physiological state of a test subject according to claim 1 and by a device for determining a physiological state of a test subject according to claim 12 of the present technique. Advantageous embodiments of the present technique are

provided in dependent claims. Features of claim 1 may be combined with features of claims dependent on claim 1, and features of these dependent claims can be combined together. Similarly, features of claim 12 may be combined with features of claims dependent on claim 12, and features of these dependent claims can be combined together.

According to an aspect of the present technique a method for determining a physiological state of a test subject is presented. In the method, a first VOC pattern is determined from a first test medium and a second VOC pattern is

determined from a second test medium, either simultaneously or successively. The first VOC pattern has a first group of VOCs and includes one or more VOCs detected in the first test medium and a concentration of each of the one or more VOCs of the first group of VOCs. The second VOC pattern has a second group of VOCs and includes one or more VOCs detected in the second test medium and a concentration of each of the one or more VOCs of the second group of VOCs. Subsequently in the method the first VOC pattern and the second VOC pattern are combined together to obtain a ^xVOCome' pattern. Finally, in the method the VOCome pattern is compared to a reference pattern. The reference pattern comprises a collection of different VOCs and concentrations of each of the different VOCs and represents a predicted known physiological state of the test subject. A combination of VOC patterns i.e. VOCome pattern generated from the first and the second VOC patterns ensures that the most prominent VOCs present in each of the VOC patterns are represented when the VOCome pattern is compared to the reference pattern, this in turn ensures an increased accuracy compared to an instance where a VOC pattern obtained from only one test medium is compared to a reference. Furthermore, by generating the VOCome pattern from different test mediums obtained from all different viable sample sources of the test subject a VOC pattern for

approximately the entire physiology of the test subject is generated which helps to assess holistically the VOC

manifested physiological condition or state of the test subj ect .

In an embodiment of the method, the method further includes determining one or more additional VOC patterns from one or more additional test mediums. The determining of the one or more additional VOC patterns is either performed

simultaneously or successively along with the determining of the first and the second VOC pattern. Each of the one or more additional VOC patterns has an additional group of VOCs including one or more VOCs detected in the additional test medium and a concentration of each of the one or more VOCs of the additional group of VOCs. In this embodiment of the method, in combining the first VOC pattern and the second VOC pattern the one or more additional VOC patterns is combined along with the first VOC pattern and the second VOC pattern to obtain the VOCome pattern. Thus VOCome pattern is

generated by combining VOC patterns from more than two test mediums. The present technique includes generation of VOCome pattern from two or more of the additional test mediums along with the first and the second test medium and thus the VOCome pattern generated or obtained in the present technique approximately represents the entire physiology of the test subject which helps to assess holistically the VOC manifested physiological condition or state of the test subject.

In another embodiment of the method, each of the one or more VOCs of the one or more additional group of VOCs is different from each of the one or more VOCs of the first and the second group of VOCs. Thus the VOCome pattern represents a holistic and diverse VOC profile of the test subject.

In another embodiment of the method, each of the one or more additional group of VOCs and the first and the second group of VOCs comprises at least one common VOC. Thus a change in concentration of a particular VOC i.e. the common VOC is studied .

In another embodiment of the method, the VOCs in each of the additional group of VOCs are VOCs commonly occurring for the corresponding additional test medium and not representing a biomarker for a specific pathological condition of the test subject. Thus, there is no need of detecting special types of VOCs that are present only in diseased individuals or

physiologically unique test subjects and thus the method is not dependent on special type of VOCs thereby increasing the applicability of the method.

In another embodiment of the method, each of the test mediums is one selected from the following: a urine sample obtained from the test subject, a head space of an urine sample obtained from the test subject, a breath sample obtained from the test subject, a body fluid sample obtained from the test subject, a head space of a body fluid sample obtained from the test subject, a fecal sample obtained from the test subject, a head space of a fecal sample obtained from the test subject and an air over skin sample obtained from the test subject. In this embodiment each of the test mediums is distinct from one another. Thus each of the test medium i.e. the first test medium, the second test medium and each of the additional test medium is distinct from one another and this helps in creating a holistic and diverse VOC profile of the test subject. Furthermore, the test mediums are obtained non- invasively and thus the method of the present technique is a non-invasive method.

In another embodiment of the method, in comparing the VOCome pattern to the reference pattern, the predicted known

physiological state of the test subject is one of a

physiologically normal state and a physiologically abnormal state. Thus if the reference pattern represents the

physiologically normal state, and if the VOCome pattern matches the reference state then it may be concluded that the physiological state of the test subject is as is desired in a healthy test subject, or vice versa. However, if the

reference pattern represents the physiologically abnormal state, and if the VOCome pattern matches the reference state then it may be concluded that the physiological state of the test subject is as is in an unhealthy test subject, or vice versa. Moreover, by the comparison of the VOCome pattern with the reference pattern the severity of physiological

abnormality may also be determined. In another embodiment of the method, each of the one or more VOCs of the first group of VOCs is different from each of the one or more VOCs of the second group of VOCs. Thus the VOCome pattern represents a holistic and diverse VOC profile of the test subject.

In another embodiment of the method, each of the first group of VOCs and the second group of VOCs comprises at least one common VOC. Thus a change in concentration of a particular VOC i.e. the common VOC is studied.

In another embodiment of the method, the VOCs in the first group of VOCs and the VOCs in the second group of VOCs are VOCs commonly occurring for the first test medium and the second test medium, respectively, and not representing a biomarker for a specific pathological condition of the test subject. The commonly occurring VOCs are not biomarkers or representative of a biomarker for a specific pathological condition of the test subject. Thus, there is no need of detecting special types of VOCs that are present only in diseased individuals or physiologically unique test subjects and thus the method is not dependent on special type of VOCs thereby increasing the applicability of the method.

In another embodiment of the method, each of the VOC patterns is determined by using one of Gas Chromatography (GC) , Mass spectrometry (MS) , Gas Chromatography-Mass Spectrometry (GC- MS), Gas Chromatography-tandem Mass Spectrometry (GC-MS/MS) , Ion-mobility spectrometry (IMS), Solid-phase microextraction Gas Chromatography-Mass Spectrometry (SPME-GC-MS) , and a combination thereof. These present simple and reliable techniques to implement the method of the present technique. According to an aspect of the present technique a device for determining a physiological state of a test subject is presented. The device includes a first module, a second module, a combining module and a comparing module. The first module is configured to determine a first VOC pattern from a first test medium. The first VOC pattern includes a first group of VOCs including one or more VOCs detected in the first test medium and a concentration of each of the one or more VOCs of the first group of VOCs. The second module is configured to determine a second VOC pattern from a second test medium. The second VOC pattern includes a second group of VOCs including one or more VOCs detected in the second test medium and a concentration of each of the one or more VOCs of the second group of VOCs. The combining module is configured to combine the first VOC pattern and the second VOC pattern to obtain a VOCome pattern. The comparing module is configured to compare the VOCome pattern to a reference pattern. The reference pattern includes a collection of different VOCs and concentrations of each of the different VOCs representing a predicted known physiological state of the test subject. Thus in the device of the present

technique, a combination of VOC patterns i.e. VOCome pattern generated from the first and the second VOC patterns ensures that the most prominent VOCs present in each of the VOC patterns are represented when the VOCome pattern is compared to the reference pattern, this in turn ensures an increased accuracy compared to a device where a VOC pattern obtained from only one test medium is compared to a reference.

Furthermore, by generating the VOCome pattern from different test mediums obtained from all different viable sample sources of the test subject a VOC pattern for approximately the entire physiology of the test subject is generated by the device of the present technique which helps to assess holistically the VOC manifested physiological condition or state of the test subject.

In an embodiment of the device, the device further includes an additional module configured to determine one or more additional VOC patterns from one or more additional test mediums. Each of the one or more additional VOC patterns includes an additional group of VOCs including one or more VOCs detected in the additional test medium and a

concentration of each of the one or more VOCs of the

additional group of VOCs. In this embodiment of the device, the combining module is further configured to combine the one or more additional VOC patterns along with the first VOC pattern and the second VOC pattern to obtain the VOCome pattern. Thus the device of the present technique is capable of generating the VOCome pattern by combining VOC patterns from more than two test mediums i.e. the first and the second test mediums and the one or more of the additional test mediums. The present device includes generation of VOCome pattern from two or more of the additional test mediums along with the first and the second test medium and thus the VOCome pattern generated or obtained in the present device

approximately represents the entire physiology of the test subject which helps to assess holistically the VOC manifested physiological condition or state of the test subject.

In another embodiment of the device, the first module is configured to receive a first set of values from an

analytical device. The first set of values is indicative of the first VOC pattern. The first module is configured to generate the first VOC pattern from the first set of values so received. In this embodiment, the second module is

configured to receive a second set of values from the

analytical device. The second set of values is indicative of the second VOC pattern. The second module is configured to generate the second VOC pattern from the second set of values so received. Thus the analytical device analyses the first and the second test mediums provides the first and the second set of values to the device of the present technique. Thus analysis of the first and the second test mediums may be done remotely from the device of the present technique and only the results of the analysis in form of the first and the second set of values may be provided to the device of the present technique.

In another embodiment of the device, the additional module is configured to receive an additional set of values from the analytical device. The additional set of values is indicative of the additional VOC pattern. The additional module is configured to generate the additional VOC pattern from the additional set of values so received. Thus the analytical device analyses the one or more of the additional test mediums and provides the one or more of the additional set of values to the device of the present technique. Thus analysis of the one or more of the additional test mediums may be done remotely from the device of the present technique and only the results of the analysis in form of the one or more of the additional set of values may be provided to the device of the present technique. The present technique is further described hereinafter with reference to illustrated embodiments shown in the

accompanying drawing, in which: FIG 1 illustrates a flow chart representing a method for determining a physiological state of a test subject, and

FIG 2 schematically illustrates a device for determining the physiological state of the test subject, in accordance with aspects of the present technique.

Hereinafter, above-mentioned and other features of the present technique are described in details. Various

embodiments are described with reference to the drawing, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purpose of explanation, numerous specific details are set forth in order to provide a thorough understanding of one or more embodiments. It may be noted that the illustrated embodiments are intended to explain, and not to limit the invention. It may be evident that such embodiments may be practiced without these specific details. The idea of the technique is to use two or more test mediums obtained from different source of a test subject for example fecal sample and urine sample obtained from the same test subject and to separately determine one or more Volatile Organic Compound (VOC) naturally generated and/or excreted from body of the test subject in the different test mediums. The determination includes detection and a measure of

quantity of VOCs present in the respective test mediums. This will provide a VOC panel or VOC profile or VOC pattern for each of the test mediums. Subsequently, these different VOC panels or VOC patterns are combined to obtain a ^eta- pattern' or a pattern of VOC patterns. The ^xmeta-pattern' referred to as VOCome pattern in the present technique represents more information than a single VOC pattern. The VOCome pattern may also represent repetitive information as compared to single VOC pattern. The use of VOCome pattern to compare to reference or to draw inferences thus increases the accuracy of the result due to repetition or the increased range of the assay due to more information.

Referring to FIG 1, a flow chart representing a method 1000 for determining a physiological state of a test subject is presented. In the method 1000, a first VOC pattern is

determined from a first test medium in a step 100.

Furthermore, in the method 100 and either successively or simultaneously along with the step 100, a second VOC pattern is determined from a second test medium in a step 200. The first VOC pattern has a first group of VOCs . The first group of VOCs includes one or more VOCs detected in the first test medium and a concentration of each of the one or more VOCs of the first group of VOCs. The second VOC pattern has a second group of VOCs. The second group of VOCs includes one or more VOCs detected in the second test medium and a

concentration of each of the one or more VOCs of the second group of VOCs.

Subsequently in the method 100, the first VOC pattern

determined from step 100 and the second VOC pattern

determined from step 200 are combined together in a step 400 to obtain a VOCome pattern. Finally, in the method 1000 the VOCome pattern obtained from step 400 is compared to a reference pattern. The reference pattern represents a

predicted known physiological state of the test subject and includes a collection of different VOCs and concentrations of each of the different VOCs.

Furthermore, in the method 1000, optionally in a step 300, one or more additional VOC patterns is determined from one or more additional test mediums. The determining of the one or more additional VOC patterns is either performed

simultaneously or successively along with the step 100 or the step 200. Each of the one or more additional VOC patterns has an additional group of VOCs . Each of the one or more

additional VOC patterns includes one or more VOCs detected in the additional test medium and a concentration of each of the one or more VOCs of the additional group of VOCs. In the method 1000 including the step 300, in combining the first VOC pattern and the second VOC pattern in step 400 the one or more additional VOC patterns is combined along with the first VOC pattern and the second VOC pattern to obtain the VOCome pattern.

In the method 1000, each of the test mediums i.e. the first test medium, the second test medium and the one or more additional test medium is obtained from the same test subject and is one selected from the following: a urine sample obtained from the test subject, a head space of an urine sample obtained from the test subject, a breath sample obtained from the test subject, a body fluid sample obtained from the test subject, a head space of a body fluid sample obtained from the test subject, a fecal sample obtained from the test subject, a head space of a fecal sample obtained from the test subject and an air over skin sample obtained from the test subject. Each of the test mediums i.e. the first test medium, the second test medium and each of the additional test medium is distinct from one another. For example if the first test medium is a urine sample, the second test medium or any of the additional test mediums is not a urine sample. In such case, and just as a way of example, the second test medium may be a fecal sample

obtained from the test subject. Then any of the additional test mediums is neither a urine sample nor a fecal sample. In such case, and just as a way of example, the additional test sample may be a breath sample obtained from the test subject.

Furthermore, the in the method 1000, it may be noted that each of the test mediums i.e. the first test medium, the second test medium and each of the additional test medium is obtained non-invasively and thus the method of the present technique is a non-invasive method. In an embodiment of the present method 1000, the one or more VOCs in the first group of VOC may be all different from the one or more VOCs in the second group of VOC and the one or more VOCs in each of the additional group of VOCs may be all different from the one or more VOCs in the first and the second group of VOCs. In an alternate embodiment of the method 1000, at least one VOC out of the one or more VOCs in the first group of VOC may be same as at least one VOC out of the one or more VOCs in the second group of VOC. Optionally, at least one VOC from the one or more VOCs in each of the additional group of VOCs may be same as at least one VOC from the first group of VOCs which may in turn be same as at least one VOC from the second group of VOCs.

It may be noted that in one embodiment the VOCs in the first and the second groups of VOCs may be a commonly occurring VOC for the first and the second test medium respectively. The commonly occurring VOCs are not biomarkers or are not

representative of any biomarkers for a specific pathological condition of the test subject. Thus, the VOCs present in the first and the second groups VOCs are those VOCs that are present in normal conditions as well as in pathological conditions in the respective test mediums obtained from the test subject. The VOCs in the first and the second groups of VOCs are present in a test subject suffering or not suffering from a pathological condition. To clarify further, the VOCs detected in the first and the second test medium to determine the first and the second VOC patterns are those VOCs that are not a biomarker of any pathological conditions in the test subj ect .

Similarly, it may be noted that the VOCs in any of the additional group of VOCs may be a commonly occurring VOCs for the respective additional test medium. The commonly occurring VOCs are not biomarkers or are not representative of any biomarkers for a specific pathological condition of the test subject. Thus, the VOCs present in any of the additional group of VOCs are those VOCs that are present in normal conditions as well as in pathological conditions in the respective additional test medium obtained from the test subject. The VOCs in any of the additional group of VOCs are present in a test subject suffering or not suffering from a pathological condition. To clarify further, the VOCs detected in any of the additional group of VOCs to determine the respective additional VOC patterns are those VOCs that are not a biomarker of any pathological conditions in the test subject.

The type of VOCs in the first group of VOCs, the second group of VOCs and/or the additional group of VOCs may be one of the most represented chemical classes generally found in the first test medium, the second test medium and/or the

additional test medium, respectively. For example when the first test medium, the second test medium or any of the additional test mediums is urine or a head space of urine then the VOCs may be one or more of a ketone for example acetone, 2-butanone, 3-methyl-2-butanone, 3-methyl-2- pentanone, 2-pentanone, so on and so forth, and/or an

aldehyde for example propanal, 2-methylpropanal, 2-methyl- butanal, and so on and so forth, and/or a sulfur containing compound for example methanethiol, dimethyl sulfide (DMS) , etc.

The determination of the concentration of the VOCs in the first group VOC in the step 100 and/or the second group of VOCs in the step 200 and/or one or more of the additional group of VOCs in the step 300 is performed by using any conventionally known analytical techniques for example Gas Chromatography (GC) , Mass spectrometry (MS) , Gas

Chromatography-Mass Spectrometry (GC-MS) , Gas Chromatography- tandem Mass Spectrometry (GC-MS/MS) , Ion-mobility

spectrometry (IMS), Solid-phase microextraction Gas

Chromatography-Mass Spectrometry (SPME-GC-MS) , and a

combination thereof. The principle of use and application of these techniques are well known in art of analytical chemistry and thus not described herein in details for sake of brevity.

Subsequently, in the method 1000, the VOCome pattern is obtained in the step 400. The VOCome pattern represents a collection or combination of the first and the second VOC patterns and may additionally include one or more of the additional VOC patterns. The VOCome pattern may simply be a holistic statistical representation of each of the VOCs and their respective concentration in the first and the second VOC patterns and optionally and additionally including each of the VOCs and their respective concentration of any of the one or more additional VOC patterns. Alternatively or additionally, the VOCome pattern may represent a net

concentration for each VOC obtained by adding the

concentrations of same VOCs from the first and the second VOC patterns and optionally and additionally by adding the concentration of the same VOC from each of the one or more additional VOC patterns. The VOCome pattern may be understood as a holistic representation of each of the VOC patterns and presented either in such a way that each of the VOC patterns are individually identifiable in the VOCome pattern or in such a way that each of the VOC patterns are individually unidentifiable in the VOCome pattern.

In an embodiment of the present technique, in the method 1000, the reference pattern i.e. the predicted known

physiological state of the test subject is either a

physiologically normal state or a physiologically abnormal state. In another embodiment of the present technique, in the method 1000, the reference pattern i.e. the predicted known physiological state of the test subject may represent both a physiologically normal state as well as a physiologically abnormal state. Thus in the step 500 of the method 1000 if the VOCome pattern obtained from the step 400 matches the reference state that represents the physiologically normal state, then it may be concluded that the physiological state of the test subject is as is desired in a healthy test subject. Furthermore, in the step 500 of the method 1000 if the VOCome pattern obtained from the step 400 does not match the reference state that represents the physiologically normal state, then it may be concluded that the physiological state of the test subject is as is in an unhealthy test subj ect .

Similarly, in the step 500 of the method 1000 if the VOCome pattern obtained from the step 400 matches the reference state that represents the physiologically abnormal state, then it may be concluded that the physiological state of the test subject is as is in an unhealthy test subject.

Furthermore, in the step 500 of the method 1000 if the VOCome pattern obtained from the step 400 does not match the

reference state that represents the physiologically abnormal state, then it may be concluded that the physiological state of the test subject is as is desired in a healthy test subject. Furthermore, by the comparison of the VOCome pattern with the reference pattern the severity of physiological abnormality may also be determined.

As used herein the term 'reference pattern' may include one or more VOC patterns i.e. different VOCs and their respective concentrations, for a defined set of individuals of a

relevant demographic group to which test subject may be identified with or compared with. The size and

characteristics of the set of individuals and the relevant demographic group may vary from one application of the method 1000 to another. In an embodiment, the reference pattern is based on observed results for a large number of individuals for example, collected in clinical trials. The reference pattern may include range limits, generally a range of standard deviations from the average result. The reference pattern may include concentrations of VOCs that represent a range of values that can be attributed to a normal or

clinically healthy physiological state comparable to the test subject being probed. Alternatively or simultaneously, the reference pattern may include concentrations of VOCs that represent a range of values that can be attributed to a abnormal or clinically unhealthy physiological state

comparable to the test subject being probed. Thus in the method 1000, in comparing 500 the VOCome pattern to the reference pattern, the physiological state of the test subject is determined to be either physiologically normal or physiologically abnormal.

Referring to FIG 2, a device 1 for determining a

physiological state of a test subject is presented. The device 1 includes a first module 10, a second module 20, a combining module 40 and a comparing module 50. The first module 10 is configured to determine a first VOC pattern from a first test medium. The first VOC pattern and the first test medium are same as described in reference to FIG 1. The second module 20 is configured to determine a second VOC pattern from a second test medium. The second VOC pattern and the second test medium are same as described in reference to FIG 1. The device 1 may additionally include one or more additional modules 30 configured to determine one or more additional VOC patterns from one or more additional test mediums. It may be noted that although only one additional module has been depicted in FIG 2, it is well within the scope and spirit of the present technique that device 1 includes two or more of such additional modules 30. The additional VOC patterns and the additional test mediums are same as described in reference to FIG 1. The combining module 40 is configured to combine the first VOC pattern and the second VOC pattern to obtain a VOCome pattern. In another embodiment the combining module 40 is configured to combine the first VOC pattern, the second VOC pattern and one or more of the additional VOC patterns to obtain the VOCome pattern. The comparing module 50 is configured to compare the VOCome pattern to a reference pattern. The VOCome pattern and the reference pattern are same as described in reference to FIG 1. In an embodiment of the device 1, the first module 10 and/or the second module 20 and/or the one or more additional modules 30 receive a first set of values, a second set of values and one or more additional set of values from an analytical device 90. The analytical device 90 analyses the different test mediums i.e. the first test medium, the second test medium and optionally and additionally the one or more additional test mediums and provides the first set and the second set of values and optionally and additionally the one or more additional set of values to the device 1, more particularly to the first module 10, the second module 20 and the one or more additional modules 30 to determine the first VOC pattern, the second VOC pattern and the one or more additional VOC patterns, respectively. The first module 10, the second module 20 and/or the one or more additional modules 30 may be realized as independent parts or may be one and the same part performing the function of each of the modules 10, 20 and 30. The analytical device 90 is a device using any conventionally known analytical techniques for example Gas Chromatography (GC) , Mass spectrometry (MS) , Gas Chromatography-Mass

Spectrometry (GC-MS) , Gas Chromatography-tandem Mass

Spectrometry (GC-MS/MS) , Ion-mobility spectrometry (IMS), Solid-phase microextraction Gas Chromatography-Mass

Spectrometry (SPME-GC-MS) , and a combination thereof. The principle of use and application of such analytical devices 90 are well known in art of analytical chemistry and thus not described herein in details for sake of brevity.

The first module 10, the second module 20 and the additional module 30 may receive from the analytical device 90 values that are the concentration of the respective groups of VOCs in the respective test mediums or may receive from the analytical device 90 other values that are then used by the first module 10, the second module 20 and the additional modules 30 to calculate the concentrations of the respective groups of VOCs in the respective test mediums. Furthermore, the first set of values, the second values and, optionally the additional set of values may be received by the first module 10, the second module 20, and the additional module directly from the analytical device 90 or may be received through an intermediate link for example by manual input by an operator who receives the first and the second set values, and optionally the additional set of values, and then feeds them into the first module 10 and the second module 20, and the additional module 30, respectively. Thus analysis of different test mediums i.e. the first test medium, the second test medium, and optionally the one or more of the additional test mediums may be done remotely from the device 1, and only the results of the analysis may be provided to the device 1 of the present technique.

In an embodiment of the device 1, the device 1 includes a memory module 60. In this embodiment of the device 1, the reference pattern is stored in the memory module 60 and the comparing module 50 obtains the reference pattern from the memory module 60.

Alternatively, in the device 1 with or without the memory module 60, the reference pattern may be provided from an external source at every usage of the device 1.

While the present technique has been described in detail with reference to certain embodiments, it should be appreciated that the present technique is not limited to those precise embodiments. Rather, in view of the present disclosure which describes exemplary modes for practicing the invention, many modifications and variations would present themselves, to those skilled in the art without departing from the scope and spirit of this invention. The scope of the invention is, therefore, indicated by the following claims rather than by the foregoing description. All changes, modifications, and variations coming within the meaning and range of equivalency of the claims are to be considered within their scope.

Claims

Patent claims

1. A method (1000) for determining a physiological state of a test subject, the method (1000) comprising:

- determining (100) a first VOC pattern from a first test medium, wherein the first VOC pattern comprises a first group of VOCs including one or more VOCs detected in the first test medium and a concentration of each of the one or more VOCs of the first group of VOCs,

- determining (200) a second VOC pattern from a second test medium, wherein the second VOC pattern comprises a second group of VOCs including one or more VOCs detected in the second test medium and a concentration of each of the one or more VOCs of the second group of VOCs,

- combining (400) the first VOC pattern and the second VOC pattern to obtain a VOCome pattern, and

- comparing (500) the VOCome pattern to a reference pattern, wherein the reference pattern comprises a collection of different VOCs and concentrations of each of the different VOCs and represents a predicted known physiological state of the test subject.

2. The method (1000) according to claim 1 further comprising:

- determining (300) one or more additional VOC patterns from one or more additional test mediums, wherein each of the one or more additional VOC patterns comprises an additional group of VOCs including one or more VOCs detected in the additional test medium and a concentration of each of the one or more VOCs of the additional group of VOCs, and

- wherein in combining (400) the first VOC pattern and the second VOC pattern the one or more additional VOC patterns is combined along with the first VOC pattern and the second VOC pattern to obtain the VOCome pattern.

3. The method (1000) according to claim 2, wherein each of the one or more VOCs of the one or more additional group of VOCs is different from each of the one or more VOCs of the first and the second group of VOCs.

4. The method (1000) according to claim 2, wherein each of the one or more additional group of VOCs and the first and the second group of VOCs comprises at least one common VOC .

5. The method (1000) according to any of claims 2 to 4, wherein the VOCs in each of the additional group of VOCs are VOCs commonly occurring for the corresponding additional test medium and not representing a biomarker for a specific pathological condition of the test subject.

6. The method (1000) according to any of claims 1 to 5, wherein each of the test mediums is selected from a urine sample obtained from the test subject, a head space of an urine sample obtained from the test subject, a breath sample obtained from the test subject, a body fluid sample obtained from the test subject, a head space of a body fluid sample obtained from the test subject, a fecal sample obtained from the test subject, a head space of a fecal sample obtained from the test subject and an air over skin sample obtained from the test subject, and wherein each of the test mediums is distinct from one another.

7. The method (1000) according to any of claims 1 to 6, wherein in comparing (500) the VOCome pattern to the

reference pattern, the predicted known physiological state of the test subject is one of a physiologically normal state and a physiologically abnormal state.

8. The method (1000) according to any of claims 1 to 7, wherein each of the one or more VOCs of the first group of VOCs is different from each of the one or more VOCs of the second group of VOCs.

9. The method (1000) according to any of claims 1 to 7, wherein each of the first group of VOCs and the second group of VOCs comprises at least one common VOC.

10. The method (1000) according to any of claims 1 to 9, wherein the VOCs in the first group of VOCs and the VOCs in the second group of VOCs are VOCs commonly occurring for the first test medium and the second test medium, respectively, and not representing a biomarker for a specific pathological condition of the test subject.

11. The method (1000) according to any of claims 1 to 10, wherein each of the VOC patterns is determined by using one of Gas Chromatography (GC) , Mass spectrometry (MS) , Gas

spectrometry (IMS), Solid-phase microextraction Gas

Chromatography-Mass Spectrometry (SPME-GC-MS) , and a

combination thereof.

12. A device (1) for determining a physiological state of a test subject, the device (1) comprising:

- a first module (10) configured to determine a first VOC pattern from a first test medium, wherein the first VOC pattern comprises a first group of VOCs including one or more VOCs detected in the first test medium and a concentration of each of the one or more VOCs of the first group of VOCs,

- a second module (20) configured to determine a second VOC pattern from a second test medium, wherein the second VOC pattern comprises a second group of VOCs including one or more VOCs detected in the second test medium and a

concentration of each of the one or more VOCs of the second group of VOCs,

- a combining module (40) configured to combine the first VOC pattern and the second VOC pattern to obtain a VOCome

pattern, and

- a comparing module (50) configured to compare the VOCome pattern to a reference pattern, wherein the reference pattern comprises a collection of different VOCs and concentrations of each of the different VOCs and represents a predicted known physiological state of the test subject.

13. The device (1) according to claim 12, the device further comprising :

- an additional module (30) configured to determine one or more additional VOC patterns from one or more additional test mediums, wherein each of the one or more additional VOC patterns comprises an additional group of VOCs including one or more VOCs detected in the additional test medium and a concentration of each of the one or more VOCs of the

additional group of VOCs, and

- wherein the combining module (40) is further configured to combine the one or more additional VOC patterns along with the first VOC pattern and the second VOC pattern to obtain the VOCome pattern.

14. The device (1) according to claim 12 or 13, wherein:

- the first module (10) is configured to receive a first set of values from an analytical device (90) wherein the first set of values is indicative of the first VOC pattern and the first module (10) is configured to generate the first VOC pattern from the first set of values so received, and

- the second module (20) is configured to receive a second set of values from the analytical device (90) wherein the second set of values is indicative of the second VOC pattern and the second module (20) is configured to generate the second VOC pattern from the second set of values so received.

15. The device (1) according to claim 13 and 14, wherein the additional module (30) is configured to receive an additional set of values from the analytical device (90) wherein the additional set of values is indicative of the additional VOC pattern and the additional module (30) is configured to generate the additional VOC pattern from the additional set of values so received.