WO2016037661A1

WO2016037661A1 - A helicobacter pylori sensor based on optical sensing

Info

Publication number: WO2016037661A1
Application number: PCT/EP2014/069496
Authority: WO
Inventors: Patrick Fröse; Erhard Magori; Roland Pohle; Evamaria STÜTZ; Angelika Tawil; Oliver von Sicard
Original assignee: Siemens Aktiengesellschaft
Priority date: 2014-09-12
Filing date: 2014-09-12
Publication date: 2016-03-17

Abstract

A Helicobacter pylori sensor for analyzing a test sample for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample is presented. The Helicobacter pylori sensor includes an optical wave guide having a core and a cladding. The cladding at least partially covers a surface of the core such that a light wave introduced into the core undergoes total internal reflection in the optical wave guide. At least a part of the cladding includes a layer of silver arranged to contact the test sample to be analyzed. On contacting the layer of silver with the test sample, the extent of ammonia present in the test sample is determinable by measuring an intensity of the light wave obtained out of the core and/or by measuring a change in polarity of the light wave obtained out of the core.

Description

A Helicobacter pylori sensor based on optical sensing This invention relates generally to a sensor for analyzing a test sample for presence of Helicobacter pylori and more par^¬ ticularly to a sensor for Helicobacter pylori based on optical sensing. Helicobacter pylori (hereinafter referred to as, HBP) are rod-shaped bacteria, which can colonize the human stomach and are responsible for a number of gastrointestinal disorders. Besides other pathological conditions caused by HBP, the gastrointestinal disorders include peptic ulcers such as stomach ulcers and duodenal ulcers. In chronic conditions, HBP can also cause stomach cancer. The prevalence of HBP is about 50% worldwide. Therefore, an investigation of infection with HBP represents an integral part of the diagnosis of gastrointes^¬ tinal diseases.

In modern medicine, a HBP infection may, for example, be treated with eradication therapy, that involves simultaneous^¬ ly using a combination of different antibiotics. However, be^¬ fore such eradication therapy can be started, an exact diag- nosis is necessary.

For HBP detection, various direct and indirect detection methods are known, for example, non invasive testing can be performed with a blood antibody test, stool antigen test, urine ELISA test or with the carbon urea breath test (in which the patient drinks 14C—labeled urea or 13C-labeled urea, which the HBP metabolizes, producing labeled carbon dioxide that can be detected in the breath of the patient) . Another method for detecting H. pylori infection is the so called endoscopy or gastroscopy method. In this method, the investigator i.e. the gastroenterologist performs a biopsy on a tissue sample collected from the gastrointestinal tract of the test subject. The biopsy involves a rapid urease test, histological examinations, and microbial culture from the tissue sample. In rapid urease test, the biopsy sample is placed in a test medium. The test medium contains a nutrient solution for HBP, urea and an indicator such a phenol red. If HBP is present in the biopsy sample, the HBP produces urease that hydrolyzes urea to ammonia and carbon dioxide. In presence of ammonia the pH of the medium is raised and thus the color of the specimen changes from yellow (urease from HBP not present) to red (urease from HBP present) . However, all of these detection methods as well as other known methods have their drawbacks such as delay in getting test results, being unpleasant to the test subject i.e. the patient, and being expensive.

Another technique for examination of the stomach to detect a settlement of HBP is disclosed in O2010108759 Al which attempts to provide an alternate to the above disclosed test methods. WO2010108759 Al presents a Helicobacter pylori sen- sor. The Helicobacter pylori sensor comprises a slide with a measuring area, a first electrode made of a precious metal which cannot be attacked by hydrochloric acid, and a second electrode which is made of silver and has a silver chloride layer, wherein the first electrode and the second electrode extend at least partially into the measuring area, and a change in an electrical variable can be measured when the measuring area and the two electrodes are at least partially wetted with a measurement solution and when ammonia is present in the measurement solution between the first electrode and the second electrode. The Helicobacter pylori sensor according to the disclosure in WO2010108759 Al is compact and of simple design and makes it possible to reliably detect Helicobacter pylori in a very short time. However, the Helicobacter pylori sensor of WO2010108759 Al has its drawbacks. Such a sensor when used in vivo and or in vitro will result in loss of one of the electrode i.e. the AgCl/Ag electrode and will be ruined for future usage. Fabri- eating the lost electrode sensor with all its proper electrical connections in a ruined sensor will be cumbersome. This will necessitate replacement of the entire sensor. Thus, the above mentioned techniques for detection of HBP are based on complex chemical tests and/or electrical parameters that need sophisticated electrical sensors and complex and very careful handling of the electrical sensors to make measurements. Moreover, there is exists a possibility of electri- cal interference in the test results from other undesired electrochemical activities at the electrodes. Thus, there exists a need for a simple technique of detection which is not based on chemical or electrical sensing mechanisms. It is therefore an object of the present invention to provide a technique of determining Helicobacter pylori based on optical sensing.

This object is achieved by a Helicobacter pylori sensor de- scribed in claim 1 and by the method described in claim 14.

The dependent claims describe advantageous embodiments of the Helicobacter pylori sensor and the method.

According to an aspect of the present technique, a Helicobac- ter pylori sensor for analyzing a test sample for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample is presented. The Helicobacter pylori sensor includes an optical wave guide having a core and a cladding. The cladding at least partially covers a surface of the core such that a light wave introduced into the core undergoes total internal reflection in the optical wave guide. At least a part of the cladding includes a layer of silver arranged to contact the test sample to be analyzed. On contacting the layer of silver with the test sample, the extent of ammonia present in the test sample is determinable by measuring an intensity of the light wave obtained out of the core and/or by measuring a change in polarity of the light wave obtained out of the core. The layer of silver is func- tionalized by use of hydrochloric acid to convert at least some of the silver in the layer to silver chloride. The func- tionalization may be achieved before contacting the layer with the test sample, or may be functionalized by the chlo- ride ions present in the test sample. Thus, when ammonia is present in the test sample the layer of silver chloride is depleted by formation of readily water soluble silver diamine complex, and thus the intensity of the light wave introduced into the core on undergoing total internal reflection at the layer is changed and this change is detected by measuring the intensity of the light wave obtained out of the core and/or by measuring the change in polarity of the light wave obtained out of the core. In one embodiment of the Helicobacter pylori sensor, the layer of silver comprises silver chloride. Thus, the requirement of functionalizing the layer is obviated.

In another embodiment of the Helicobacter pylori sensor, the optical wave guide is an optical fiber. The optical fiber is a readily available, economical and compact optical wave guide and thus the Helicobacter pylori sensor fabricated us^¬ ing the optical fiber is easy to manufacture, inexpensive and compact .

In another embodiment, the Helicobacter pylori sensor includes an optical source adapted to provide the light wave into the core. Thus, need for an external optical source is obviated. The Helicobacter pylori sensor is self contained and thus easy to use.

In another embodiment of the Helicobacter pylori sensor, the optical source is a Light-emitting diode (LED) . The LED is a readily available, economical and compact optical source and thus the Helicobacter pylori sensor fabricated using the LED is easy to manufacture, inexpensive and compact. In another embodiment of the Helicobacter pylori sensor, the optical source is a Laser diode. The Laser diode is readily available, economical and compact and thus the Helicobacter pylori sensor fabricated using the Laser diode is easy to manufacture, inexpensive and compact.

In another embodiment of the Helicobacter pylori sensor, the core is an elongated structure having a proximal end and a distal end. The proximal end is adapted to be introduced into the test sample, and the optical source is located at the distal end. Thus when the Helicobacter pylori sensor is used in vivo i.e. to probe inside the body of a test subject, then the optical source is not required to be introduced inside the body of the test subject. This makes the use of the Heli- cobacter pylori sensor easy for a medical practitioner and less inconvenient for the test subject.

In another embodiment, the Helicobacter pylori sensor includes a detector positioned at the proximal end and adapted to detect the intensity of the light wave obtained out of the core and/or to measure the change in polarity of the light wave obtained out of the core. This provides a simple design for the Helicobacter pylori sensor and is especially useful for design of the Helicobacter pylori sensor to be used in vitro.

In another embodiment, the Helicobacter pylori sensor further includes a detector adapted to detect the intensity of the light wave obtained out of the core and/or by measuring a change in polarity of the light wave obtained out of the core. The core is an elongated structure having a proximal end and a distal end. The proximal end is adapted to be introduced into the test sample, and the detector is located at the distal end. In this embodiment, the Helicobacter pylori sensor also includes a reflector positioned at the proximal end of the core and adapted to reflect the light wave towards the distal end. Thus when the Helicobacter pylori sensor is used in vivo i.e. to probe inside the body of a test subject, then the detector is not required to be introduced inside the body of the test subject. This makes the use of the Helico^¬ bacter pylori sensor easy for a medical practitioner and less inconvenient for the test subject.

In another embodiment of the Helicobacter pylori sensor, the optical source is located at the distal end. The detector is also located at the distal end. Thus when the Helicobacter pylori sensor is used in vivo i.e. to probe inside the body of a test subject, then the optical source as well as the de^¬ tector are not required to be introduced inside the body of the test subject. This makes the use of the Helicobacter pylori sensor easy for a medical practitioner and less inconvenient for the test subject.

In another embodiment of the Helicobacter pylori sensor, the detector is a photodiode. The photodiode is a readily available, economical and compact and thus the Helicobacter pylori sensor fabricated using the photodiode is easy to manufac- ture, inexpensive and compact.

In another embodiment of the Helicobacter pylori sensor, the detector is a spectrophotometer. The spectrophotometer pro^¬ vides detection of intensities of light over a wide spectrum and thus the Helicobacter pylori sensor can be used for with different wavelengths of light waves. Moreover, the spectrophotometer is readily available and its working is well known thus the Helicobacter pylori sensor fabricated using the spectrophotometer is easy to manufacture, and simple to use for detection of the light wave obtained out of the core.

In another embodiment of the Helicobacter pylori sensor, the optical wave guide except the layer of silver is adapted to be inert to the test sample to be analyzed with respect to hydrochloric acid and/or ammonia. This can be achieved by ei^¬ ther using a cladding material, besides the layer of silver, that is inert to the test sample to be analyzed with respect to hydrochloric acid and/or ammonia or by using a housing which is made of a material that is inert to the test sample to be analyzed with respect to hydrochloric acid and/or ammo^¬ nia and where the housing is such that it allows only exposure of the layer of silver to the test sample. Since the op- tical wave guide except the layer of silver does not chemically react with hydrochloric acid and/or ammonia, the meas^¬ urements made by the Helicobacter pylori sensor are more accurate as they represent measurements resulting from a reaction between ammonia and the layer of silver chloride only.

According to another aspect of the present technique, a method for analyzing a test sample for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample is presented. The method uses a Helicobacter py- lori sensor according to the previous aspect of the present technique. In the method, the layer of silver of the Helicobacter pylori sensor is contacted with the test sample to be analyzed. A light wave is introduced into the core of the op^¬ tical wave guide of the Helicobacter pylori sensor. Subse- quently, an intensity of the light wave obtained out of the core of the optical wave guide is measured and/or a change in polarity of the light wave obtained out of the core is meas^¬ ured. Finally, the extent of ammonia present in the test sam^¬ ple is calculated from the intensity of the light wave ob- tained out of the core.

In one embodiment of the method, the light wave introduced into the core of the optical wave guide of the Helicobacter pylori sensor is reflected towards the optical source before measuring the intensity of the light wave obtained out of the core. Thus when the method is performed in vivo i.e. to probe inside the body of a test subject, the optical source as well as the detector are not required to be introduced inside the body of the test subject. This makes the method easy for a medical practitioner and less inconvenient for the test sub^¬ ject . It may be noted that by using the present technique a pres^¬ ence or absence of the ammonia in the test sample, and ac^¬ cordingly the presence or absence of HBP in the test sample, may be detected. Furthermore, in test samples where the ammo- nia is found or detected to be present, an extent of ammonia present i.e. an amount of ammonia present in the test sample may be determined which leads to determination of an amount of the HBP present in the test sample. The present technique is further described hereinafter with reference to illustrated embodiments shown in the accompanying drawings, in which:

FIG 1 is a schematic representation of an exemplary em- bodiment of a cross-section of a Helicobacter pylori sensor in accordance with aspects of the present technique;

FIG 2 is a schematic representation of another exemplary embodiment of a cross-section the Helicobacter pylori sensor;

FIG 3 is a schematic representation of another exemplary embodiment of the Helicobacter pylori sensor of FIG 1 depicting working of the Helicobacter pylori sensor;

FIG 4 is a schematic representation of another exemplary embodiment of the Helicobacter pylori sensor of FIGs 1 and 3 further depicting working of the Helicobacter pylori sensor;

FIG 5 is a schematic representation of another exemplary embodiment of a cross-section the Helicobacter pylori sensor depicting a reflector; FIG 6 is a schematic representation of another exemplary embodiment of a cross-section the Helicobacter py^¬ lori sensor depicting a housing; and FIG 7 is a flow chart illustrating a method for analyzing a test sample of a test subject for presence of Helicobacter pylori, in accordance with aspects of the present technique. Hereinafter, above-mentioned and other features of the pre^¬ sent technique are described in details. Various embodiments are described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purpose of ex- planation, 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 basic principle of the detection of Helicobacter pylori (hereinafter HBP) is based on detecting the presence or ab^¬ sence of ammonia (NH₃) in the test sample. HBP characteristi- cally produces bacterial urease, an enzyme that catalyzes the hydrolysis of urea [(NH₂)₂CO] into carbon dioxide (CO₂) and ammonia as shown in the following chemical equation:

(NH₂)₂CO + H₂0 → C0₂ + 2NH₃

Ammonia is not present under normal circumstances in a hollow organ of the gastrointestinal tract (hereinafter, GI tract) such as the stomach. Even if present, ammonia is present only in insignificantly small amounts. However, in test samples or in test subjects i.e. patients suffering from HBP infection the amount of ammonia present in the GI tract or in the test culture to which the test sample is added is significantly increased due to the bacterial urease produced by HBP. Thus, determining an extent of ammonia present in the test sample is a definitive conclusion of the presence of HBP.

Detection of ammonia is performed using silver chloride (AgCl) . Ammonia in aqueous state reacts with AgCl in solid state to form a readily water soluble silver diamine complex as per the following chemical equation:

AgCl(s) + 2NH₃(aq) → [Ag (NH₃) ₂ ] ⁺ (aq) + Cl^"(aq)

This results in a loss of silver chloride by dissolution into the test sample. This loss of silver chloride is optically detected to conclude the presence of ammonia which in turn is definitively used to conclude a presence of bacterial urease and final conclusion is presence of HBP.

The above described principle of determining presence of HBP is used in the present technique. FIG 1 schematically represents an exemplary embodiment of a Helicobacter pylori sensor 100 in accordance with aspects of the present technique.

The Helicobacter pylori sensor 100 (hereinafter HBP sensor 100) is used for analyzing a test sample 2 of a test subject for presence of HBP in the test sample 2. As mentioned above, the presence of HBP is analyzed by determining an extent of ammonia present in the test sample 2. For the purposes of the present technique, the term "analyzing" or like terms, as used herein, means probing, checking, evaluating, testing, scrutinizing or examining the test sample 2. The phrase "analyzing the test sample 2 for presence of Helicobacter pylori" means analyzing the test sample 2 to determine or detect a presence of HBP and may optionally in^¬ clude quantifying HBP in the test sample 2. The "test sample" 2, as used herein, means and includes an in vivo sample or in vitro sample. For probing the test sample 2 in vivo, the HBP sensor 100 is required to be introduced inside the body of the test subject i.e. the patient. This can be achieved by integrating the HBP sensor 100 with a suitable invasive device such as a gastroscope, an endoscope, an en^¬ doscopy capsule, a biopsy catheter, so on and so forth. An example of the test sample 2, in vivo, may be, but not limited to, gastric juice within the stomach of the test subject or contents or mediums within other parts of the GI tract.

For probing the test sample 2 in vitro, the test sample 2 may be a biological specimen collected from the test subject for example a specimen of the gastric juice of the test subject. The test sample 2, in vitro, may also include test sample 2 prepared with additives such as a suitable test buffer or water for dilution.

The phrase "extent of ammonia", as used herein means, the ab^¬ sence or presence of ammonia i.e. zero amount of ammonia or non-zero amount of ammonia. Furthermore, the phrase "extent of ammonia", when in non-zero amount i.e. when ammonia is present in the test sample 2, includes the quantitative as^¬ sessment of the ammonia present. Now referring to FIG 1, the HBP sensor 100 includes an optical wave guide 10 having a core 20 and a cladding 30. The cladding 30 at least partially covers a surface 22 of the core 20 such that a light wave 5 introduced into the core 20 undergoes total internal reflection in the optical wave guide 10. At least a part of the cladding 30 includes a layer 40 of silver. The layer 40 is arranged in the HBP sensor to contact the test sample 2 to be analyzed. On contacting the layer 40 with the test sample 2, the extent of ammonia present in the test sample 2 is determinable by measuring an intensity of the light wave 5 obtained out of the core 20 and/or by meas^¬ uring a change in polarity of the light wave 5 obtained out of the core 20. Hereinafter the intensity has been used in the present disclosure for the purposes of simplicity and ex- planation, but it may be appreciated by one skilled in the art of optics that the present technique is easily realizable by using measurements pertaining to change in polarity of the light wave 5 obtained out of the core 20.

The layer 40 of silver is functionalized by converting at least some of the silver in the layer 40 to silver chloride. The functionalization may be achieved before contacting the layer 40 with the test sample 2. This can be achieved either by reacting it with chloride ion, for example by dipping or spraying the layer 40 having silver with hydrochloric acid. The functionalization of the layer 40 may be achieved either before the test sample 2 is contacted with the layer 40 or during the contact of the test sample 2 with the layer 40, if chloride ions are available in the test sample 2. If the test sample 2 is gastric juice, in vivo or in vitro, it contains hydrochloric acid which helps to functionalize the layer 40.

The core 20 is formed of a material which has a different re- fractive index compared to a refractive index of a material forming the cladding 30. In one embodiment of the HBP sensor 100, the refractive index of the core 20 is higher than the refractive index of the cladding 30. Furthermore, the materi^¬ al from which the core 20 is formed is selected to have a re- fractive index different from the refractive index of silver or silver chloride, and more precisely the material from which the core 20 is formed is selected to have a refractive index higher than the refractive index of silver or silver chloride. In this embodiment of the HBP sensor 100, the core 30 is, but not limited to, formed of diamond whereas the cladding is formed of silver or silver chloride.

In another embodiment the optical wave guide 10 is an optical fiber. The optical fibers 10 are readily available and their working principle is well known. A part of the cladding 30 of the optical fiber 10 is replaced with layer 40 of silver or silver chloride. FIG 1, 3 and 4 are used to explain the working of the HBP sensor 100. Before contacting the layer 40 with the test sam^¬ ple 2 to be analyzed, the light wave 5 introduced in the core 20 of the HBP sensor 100 having an entirely intact function- alized layer 40 is transmitted through the core 20 in a default way, as depicted in FIG 1. During analysis of the test sample 2, when the layer 40 of the HBP sensor 100 is contacted with the test sample 2 to be analyzed and if the test sample 2 is without ammonia, then during analysis, the light wave 5 introduced in the core 20 of the HBP sensor 100 is transmitted or continues to be transmitted through the core 20 in the default way. There is no variation or change detected in the way the light wave 5 is transmitted through the core 20 because in absence of ammonia in the test sample 2, the entirely intact functionalized layer 40 of the HBP sensor 10 remains unchanged.

However, during analysis of the test sample 2, when the layer 40 of the HBP sensor 100 is contacted with the test sample 2 to be analyzed and if the test sample 2 contains ammonia, then during analysis, the light wave 5 introduced in the core 20 of the HBP sensor 100 is transmitted through the core 20 in a way different as compared to the default way. This vari^¬ ation or change detected in the way the light wave 5 is transmitted through the core 20 occurs because in the presence of ammonia in the test sample 2 the entirely intact functionalized layer 40 of the HBP sensor 10 does not remain unchanged as depicted in FIGs 3 and 4 in comparison with FIG 1 which depict successive depletion of the layer 40. As ex- plained earlier, silver chloride of the layer 40 depletes in presence of ammonia in the test sample 2. Thus if ammonia is present in the test sample 2, when the light wave 5 is introduced in the core 20 the transmission of the light wave 5 through and out of the core 20 keeps changing or completely changes during the contact. This change in transmission of the light wave 5 through and out of the core 20 is determined by measuring the intensity of the light wave 5 obtained out of the core 20. The default way of transmission for the HBP sensor 100 i.e. the transmission of the light wave 5 through the optical wave guide 10 having the layer 40 completely intact is determined. The entirely intact layer is depicted in the HBP sensor of

FIG 1. The default way of transmission for the HBP sensor 100 is correlated to a base intensity which may be determined by measuring the intensity of the light wave 5 obtained out of the core 20 before contacting the layer 40 with the test sam- pie 2 or by measuring the intensity of the light wave 5 ob^¬ tained out of the core 20 when the layer 40 is contacted with the test sample 2 which is known to not contain ammonia or by measuring the intensity of the light wave 5 obtained out of the core 20 when the layer 40 has just been contacted with the test sample 2 to be analyzed i.e. as soon as the layer 40 is contacted with the test sample 2 to be analyzed.

Subsequently, the optical wave guide 10 is exposed for a pe^¬ riod of time to the test sample 2 to be analyzed which means the layer 40 of the optical wave guide 10 is contacted for said period of time with the test sample 2 to be analyzed. On contacting for said period of time the layer 40 of the opti^¬ cal wave guide 10 with the test sample 2, if the intensity of the light wave 5 obtained out of the core 20 i.e. the light wave 5 emerging out of the core 20 after being introduced into the core 20 and subsequently undergoing transmission through the optical wave guide 10, is same as the base inten^¬ sity then this infers that the test sample 2 does not contain ammonia which in turn means that HBP is not present in the test sample 2.

However, if on contacting for said period of time the layer 40 of the optical wave guide 10 with the test sample 2, the the intensity of the light wave 5 obtained out of the core 20 is different than the base intensity then this infers that the test sample 2 contains ammonia which in turn means that HBP is present in the test sample 2. The change in the intensity of the light wave 5 obtained out of the core 20 is re- sultant from depletion of the layer 40 as depicted in FIG 3 and FIG 4.

As is clear from a comparison of FIG 1, 3 and 4, the layer 40 is gradually lost from the HBP sensor 10 until the layer 40 is completely depleted from the HBP sensor 10. If said period is a predetermined period of time, then a rate of change in intensity of the light wave 5 obtained out of the core 20 provides for a quantitative measure of a concentration of am- monia in the test sample 2, which in turn provides for quan^¬ tification of the concentration of HBP in the test sample 2. By comparing the rate of change in intensity of the light wave 5 obtained out of the core 20 to a reference such as a standard curve representing relation between different ammo- nia concentrations and related rate of change in intensity of a similar HBP sensor 100, the concentration of ammonia is determined. The method of using and creating such standard curves, also sometimes referred to as reference curves, is a well known and pervasively used standard laboratory technique and thus has not been described herein for sake of brevity.

Thus by using the present technique, on analyzing an unknown sample, a presence or absence of ammonia in the unknown sam^¬ ple is detected which means a presence or absence of HBP in the unknown sample is detected. If ammonia, and thereby the HBP, is detected to be present in the unknown sample, then furthermore an amount or concentration of ammonia in the un^¬ known sample is determined which in turn provides an quantitative assessment of an amount or concentration of HBP in the unknown sample.

In one embodiment of the HBP sensor 100, the layer 40 forms or constitutes only a part of the cladding 30 as depicted in FIG 1. However, in another embodiment of the HBP sensor 100, the layer 40 forms or constitutes the cladding 30 entirely as depicted in FIG 2. Referring to FIG 1 and FIG 2, in one embodiment, the HBP sen^¬ sor 100 includes an optical source 12. The optical source 12 provides the light wave 5 into the core 20. The optical source 12 may be such that it provides the light wave 5 hav- ing a single wavelength and/or provides the light wave 5 having a narrow range of wavelengths or provides the light wave 5 as a broadband light. The optical source 12 is selected based on one or more of wavelengths of the light wave 5 at which the difference in transmission of the light wave 5 through and out of the core 20 is specific and sensitively detectable. Thus, in one embodiment of the HBP sensor 100 the optical source 12 is a Light-emitting Diode (LED) . In another embodiment of the HBP sensor 100 the optical source 12 is an array (not shown) of a plurality of LEDs. In yet another em- bodiment of the HBP sensor 100 the optical source 12 is a Laser diode. Again, in yet another embodiment of the HBP sensor 100 the optical source 12 is an array of a plurality of Laser diodes. The optical source 12 may produce the light wave 5 in visible spectrum or Infra-red spectrum or near infra-red spectrum.

As depicted in FIGs 1 and 2, in one embodiment of the HBP sensor 100, the core 20 is an elongated structure having a proximal end 24 and a distal end 26. The proximal end 24 is configured to be introduced into the test sample 2. The configuration is achieved by positioning the layer 40 in the cladding 30 such that the layer 40 is at least present at the proximal end 24 of the core 20, as specifically shown in FIG 1. However, it may be noted that the layer 40 may extend be- yond the proximal end 24, as specifically depicted in FIG 2. The optical source 12 is located at the distal end 26. Thus, during in vivo usage of the HBP sensor 100, only the proximal end 24 of the core 20 of the HBP sensor may be required to be introduced inside the test subject. The optical source 12 lo- cated at the distal end 26 may remain outside the test sub^¬ ject. Furthermore, during in vitro usage of the HBP sensor 100, only the proximal end 24 of the core 20 of the HBP sensor may be required to be introduced into the test sample 2. The optical source 12 located at the distal end 26 may remain outside the test sample 2.

Additionally, the HBP sensor 100 includes a detector 50, 60 as depicted in FIGs 1 and 5, respectively. The detector 50, 60 detect intensity of electromagnetic radiations. The detec^¬ tor 50, 60 detects the intensity of the light wave 5 obtained out of the core 20. The detector 50, 60 may include, but not limited to, a photodiode, a spectrophotometer, and so on and so forth.

As shown in FIG 1, in one embodiment of the HBP sensor 100, the detector 50 may be positioned at the proximal end 26 of the core 20. Thus, the light wave 5 obtained out of the core 20 at the proximal end 24 of the core 20 is detected by the detector 50.

As shown in FIG 5, in another embodiment of the HBP sensor 100, the detector 60 may be positioned at the distal end 26 of the core 20 along with the optical source 12. In this embodiment the HBP sensor 100 further includes a reflector 80 positioned at the proximal end 24 of the core 20. The reflec^¬ tor 80 is a reflector of electromagnetic radiations, for ex^¬ ample a mirror, and reflects the light wave 5 traveling to the proximal end 24 within the core 20 back towards the distal end 26 of the core 20. Thus, the light wave 5 obtained out of the core 20 at the distal end 26 of the core 20 is de^¬ tected by the detector 60. Thus, during in vivo usage of the HBP sensor 100, the optical source 12 and the detector 60 lo- cated at the distal end 26 of the core 20 remain outside the test subject, and are not required to be introduced into the body of the test subject. Furthermore, during in vitro usage of the HBP sensor 100, the optical source 12 and the detector 60 located at the distal end 26 of the core 20 remain outside the test sample 2, and are not required to be introduced into the test sample 2. In an embodiment of the HBP sensor 100, the optical wave guide 10 except the layer 40 is adapted to be inert to the test sample 2 to be analyzed with respect to hydrochloric acid and/or ammonia. This can be achieved by a number of ways. One way is to select a material of the core 20 that is chemically inert or nonreactive to hydrochloric acid and/or ammo^¬ nia, for example material like diamond. Moreover, the cladding 30 besides the layer 40 is also selected to be formed of a material of that is chemically inert or nonreactive to hy- drochloric acid and/or ammonia, for example a material like an inert polymer or plastic. Another way of realizing this embodiment of the HBP sensor 100 is to use a housing 70 as shown in FIG 6 that schematically represents another exemplary embodiment of a cross-section the HBP sensor 100 de- picting the housing 70. The housing 70 is made of a material of the core 20 that is chemically inert or nonreactive to hydrochloric acid and/or ammonia for example of non reactive metals like Gold (Au) , Platinum (Pt) , etc. or of non metallic materials such as inert polymers or plastics.

As may be appreciated by a person skilled in the art of optics, the term "intensity" as used herein includes any other related measurement pertaining to the light wave 5 obtained out of the core 20 which in turn provides an indication or measurement of the intensity of the light wave 5 obtained out of the core 20.

The present technique also manifests in form of a method 1000 for analyzing a test sample 2 for presence of HBP, as depict- ed the flow chart of FIG 7, one embodiment of which has been explained hereinafter in combination with FIGs 1 to 4. In the method 1000 the test sample 2 is analyzed for presence of HBP by determining an extent of ammonia present in the test sample 2 by using the HBP sensor 100 as described hereinabove. In the method 1000, in a step 500 the layer 40 of the HBP sensor 100 is contacted with the test sample 2 to be analyzed. This means that the layer 40 is brought into physical contact with the test sample 2 or portions of the test sample 2. In a step 600, the light wave 5 is introduced into the core 20 of the optical wave guide 10 of the HBP sensor 100. The step 600 may be performed either subsequent to or simultaneously with the step 500. Subsequently, in a step 700, the intensity of the light wave 5 obtained out of the core 20 is measured. Finally, in a step 800, the extent of ammonia pre^¬ sent in the test sample 2 is calculated from the intensity of the light wave 5 obtained out of the core 20. Another embodiment of the method 1000 is explained hereinaf^¬ ter with reference to FIG 7 in combination with FIG 5. Thus, in the method 1000, in a step 650, the light wave 5 introduced into the core 20 of the optical wave guide 10 of the Helicobacter pylori sensor 100 is reflected towards the opti- cal source 12. The step 650 is performed after the step 600 and before the step 700.

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 Helicobacter pylori sensor (100) for analyzing a test sample (2) for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample (2), the Helicobacter pylori sensor (100) comprising:

- an optical wave guide (10) having a core (20) and a cladding (30), wherein the cladding (30) at least partially covers a surface (22) of the core (20) such that a light wave (5) introduced into the core (20) undergoes total internal reflection in the optical wave guide (10), wherein at least a part of the cladding (30) comprises a layer (40) of silver arranged to contact the test sample (2) to be analyzed, wherein, on contacting the layer (40) of silver with the test sample (2), the extent of ammonia present in the test sample (2) is determinable by measuring an intensity of the light wave (5) obtained out of the core (20) and/or by measuring a change in polarity of the light wave (5) obtained out of the core (20) .

2. The Helicobacter pylori sensor (100) according to claim 1, wherein the layer (40) of silver comprises silver chloride.

3. The Helicobacter pylori sensor (100) according to claim 1 or 2, wherein the optical wave guide (10) is an optical fiber .

4. The Helicobacter pylori sensor (100) according to any of claims 1 to 3, further comprising an optical source (12) adapted to provide the light wave (5) into the core (20) .

5. The Helicobacter pylori sensor (100) according to claim 4, wherein the optical source (12) is a Light-emitting diode.

6. The Helicobacter pylori sensor (100) according to claim 4, wherein the optical source (12) is a Laser diode.

7. The Helicobacter pylori sensor (100) according to any of claims 4 to 6, wherein the core (20) is an elongated struc^¬ ture having:

- a proximal end (24) adapted to be introduced into the test sample ( 2 ) , and

- a distal end (26), wherein the optical source (12) is lo^¬ cated at the distal end (26) .

8. The Helicobacter pylori sensor (100) according to claim 7, further comprising a detector (50) positioned at the proximal end (24) and adapted to detect the intensity of the light wave (5) obtained out of the core (20) and/or to detect the change in polarity of the light wave (5) obtained out of the core (20) .

9. The Helicobacter pylori sensor (100) according to any of claims 4 to 6, further comprising a detector (60) adapted to detect the intensity of the light wave (5) obtained out of the core (20) and/or to detect the change in polarity of the light wave (5) obtained out of the core (20), wherein the core (20) is an elongated structure having:

- a proximal end (24) adapted to be introduced into the test sample ( 2 ) , and

- a distal end (26), wherein the detector (60) is located at the distal end (26), and

wherein the Helicobacter pylori sensor (100) further comprises a reflector (70) positioned at the proximal end (24) of the core (20) and adapted to reflect the light wave (5) towards the distal end (26) .

10. The Helicobacter pylori sensor (100) according to claim 9, wherein the optical source (12) is located at the distal end (26) .

11. The Helicobacter pylori sensor (100) according to any of claims 8 to 10, wherein the detector (50, 60) is a photodi- ode .

12. The Helicobacter pylori sensor (100) according to any of claims 8 to 10, wherein the detector (50, 60) is a spectro^¬ photometer .

13. The Helicobacter pylori sensor (100) according to any of claims 1 to 12, wherein the optical wave guide (10) except the layer (40) of silver is adapted to be inert to the test sample (2) to be analyzed with respect to hydrochloric acid and/or ammonia.

14. A method (1000) for analyzing a test sample (2) for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample (2) by using a Helicobacter pylori sensor (100) according to any of claims 1 to 13, the method (1000) comprising:

- contacting (500) the layer (40) of silver of the Helicobacter pylori sensor (100) with the test sample (2) to be analyzed,

- introducing (600) a light wave (5) into the core (20) of the optical wave guide (10) of the Helicobacter pylori sensor (100) ,

- measuring (700) an intensity of the light wave (5) obtained out of the core (20) and/or a change in polarity of the light wave (5) obtained out of the core (20) , and

- calculating (800) the extent of ammonia present in the test sample (2) from the intensity of the light wave (5) obtained out of the core (20) and/or from the change in polarity of the light wave (5) obtained out of the core (20) .

15. The method (1000) according to claim 14, wherein the light wave (5) introduced into the core (20) of the optical wave guide (10) of the Helicobacter pylori sensor (100) is reflected (650) towards the optical source (12) before measuring (700) the intensity of the light wave (5) obtained out of the core (20) and/or the change in polarity of the light wave (5) obtained out of the core (20) .