WO2016037663A1

WO2016037663A1 - A helicobacter pylori sensor based on a chemical field-effect transistor

Info

Publication number: WO2016037663A1
Application number: PCT/EP2014/069520
Authority: WO
Inventors: Patrick Fröse; Erhard Magori; Roland Pohle; 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 at least one chemical field-effect transistor having a body terminal, a source terminal, a drain terminal formed in a semiconductor substrate. The chemical field-effect transistor further includes a gate terminal which is a layer comprising silver and overlies an electrically insulating stratum such that the gate terminal is electrically insulated by the electrically insulating stratum from a surface of the semiconductor substrate. The layer is adapted to contact the test sample to generate a potential in the layer. On contacting the layer with the test sample, the extent of ammonia present in the test sample is determinable by measuring a change in a source-drain electrical current.

Description

A Helicobacter pylori sensor based on a chemical field-effect transistor

This invention relates generally to a sensor for analyzing a test sample for presence of Helicobacter pylori and more particularly to a sensor for Helicobacter pylori based on a chemical field-effect transistor.

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 gastrointestinal diseases.

In modern medicine, a HBP infection may, for example, be treated with eradication therapy, that involves

simultaneously using a combination of different antibiotics. However, before such eradication therapy can be started, an exact diagnosis 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 hydrolizes 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 WO2010108759 Al which attempts to provide an alternate to the above disclosed test methods. WO2010108759 Al presents a Helicobacter pylori sensor. 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.

Fabricating 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.

It is therefore an object of the present invention to provide an easy to operate helicobacter pylori sensor with simple construction, and that allows easy regeneration of the sensor for further usage.

This object is achieved by a Helicobacter pylori sensor described in claim 1 and by a method described in claim 11. The dependent claims describe advantageous embodiments of the Helicobacter pylori sensor and the method.

According to a first aspect of the present technique, a

Helicobacter pylori sensor (hereinafter, HBP sensor) for analyzing a test sample of a test subject for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample, is presented. The HBP sensor includes at least one chemical field-effect transistor

(hereinafter, ChemFET) having a body terminal, a source terminal, a drain terminal, an electrically insulating stratum and a gate terminal. The body terminal is formed of a semiconductor substrate having a doping polarity. The source terminal and the drain terminal are formed within the

semiconductor substrate and are a pair of spaced apart diffusion regions located at a surface of the semiconductor substrate. The diffusion regions forming the source and the drain terminal have a doping polarity opposite to the doping polarity of the semiconductor substrate. The electrically insulating stratum overlies at least the surface of the semiconductor substrate lying between the source and the drain .

In the ChemFET of the HBP sensor, the gate terminal is a layer comprising silver. The layer of the gate terminal overlies the electrically insulating stratum such that the gate terminal is electrically insulated by the electrically insulating stratum from the surface of the semiconductor substrate. The layer is adapted to contact the test sample to generate a potential in the layer. On contacting the layer with the test sample, the extent of ammonia present in the test sample is determinable by measuring a change in a source-drain electrical current.

In an embodiment of the HBP sensor, the layer of the gate terminal comprises silver chloride. Therefore, a requirement of functionalizing the layer of the gate terminal before using to determine ammonia, if any in the sample, is

obviated . In another embodiment, the HBP sensor further includes a reference electrode connected in circuit relationship with the source and the drain through a potential source such that a reference potential is created and added to the potential generated in the layer. This provides an easy way of making measurements of the source-drain current.

In another embodiment of the HBP sensor, the reference electrode is formed of a material inert to ammonia and/or hydrochloric acid. Thus, the reference electrode does not chemically react with hydrochloric acid and/or ammonia and thus the measurements made by the HBP sensor are more

accurate as they represent measurements resulting only from a reaction between the layer of the gate terminal of the

ChemFET and ammonia, if any in the test sample, and not from a reaction between the reference electrode and the ammonia, if any in the test sample.

In another embodiment, the HBP sensor includes a plurality of the chemical field-effect transistors (hereinafter, ChemFETs) wherein the plurality comprises at least a first ChemFET and a second ChemFET and wherein a thickness of the layer in the first ChemFET is different from a thickness of the layer in the second ChemFET. Thus, by using the different thicknesses, a wide range of different extents of ammonia in the test samples may be measured. The different thicknesses also help in making measurements at different locations, with varying concentrations of ammonia, within the test subject.

In another embodiment, the HBP sensor further includes at least an ion-sensitive field-effect transistor for measuring a pH of the test sample. Since rate of reaction between the layer of the gate terminal and the ammonia, if any in the sample, depends on pH of the test sample, the potential of the layer also depends on the pH of the test sample to some degree. Thus, by knowing the pH of the test sample, a more exact determination of the extent of ammonia is possible. In another embodiment, the HBP sensor further includes a housing for protecting the at least one ChemFET. The ChemFET is positioned inside the housing such that the ChemFET except the layer of the gate terminal of the ChemFET is hermetically sealed from the test sample. Thus, no other part of the HBP sensor except the layer of the gate terminal of the ChemFET reacts with the test sample, and this ensures accuracy of the measurements. Moreover, because of the housing the longevity of the HBP sensor is increased. Furthermore, for reuse the ChemFET of the HBP sensor can be regenerated simply by restoring or depositing the layer of the gate terminal.

In another embodiment of the HBP sensor, the housing is made of a material inert to the test sample to be analyzed with respect to ammonia and/or hydrochloric acid. Being inert to ammonia and/or the hydrochloric acid, the housing does not contribute to the potential of the layer at the gate terminal and thus the measurements of the source-drain current are not affected by the housing. In another embodiment of the HBP sensor, the housing is made of an electrically insulating material. Thus, any external electrical source is obviated from interfering with the measurements of the source-drain current, thereby leading to greater accuracy of measurement of the source-drain current.

In another embodiment of the HBP sensor, the housing includes an aperture adapted to be operable to be in an open state or in a closed state. When the HBP sensor is in use with the test sample, the aperture in the open state allows the test sample to contact the layer of the ChemFET and the aperture in the closed state prevents the test sample to contact the layer of the ChemFET. Thus, by an operation of the aperture, an instance of contact of the test sample with the layer of the gate terminal and duration of contact of the test sample with the layer of the gate terminal can be controlled. According to another aspect of the present technique, a method for analyzing a test sample of a test subject for presence of Helicobacter pylori is presented. In the method, the HBP sensor, in accordance with the first aspect of the present technique, is provided. Subsequently, the test sample to be analyzed is contacted with the layer of the gate terminal of the ChemFET. Then, the change in the source-drain electric current in the semiconductor substrate is measured, and finally, the extent of ammonia present in the test sample is determined from the change in the source-drain electric current so measured. The extent of ammonia present in the test sample is indicative of presence of Helicobacter pylori in the test sample.

It may be noted that by using the present technique, a presence or absence of the ammonia in the test sample, and accordingly the presence or absence of HBP in the test sample, may be detected. Furthermore, in test samples where the ammonia 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 reference to illustrated embodiments shown in the

accompanying drawings, in which: is a schematic representation of an exemplary embodiment of a chemical field-effect transistor of a Helicobacter pylori sensor, in accordance with aspects of the present technique; is a schematic representation of another exemplary embodiment of the chemical field-effect transistor of the Helicobacter pylori sensor depicting

exemplary circuit relationship in the Helicobacter pylori sensor; is a schematic representation of another exemplary embodiment of the Helicobacter pylori sensor depicting a plurality of chemical field-effect transistor positioned in a housing of the Helicobacter pylori sensor; and 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 present 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 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 basic principle of the detection of Helicobacter pylori (hereinafter, HBP) is based on detecting the presence or absence of ammonia (NH₃) in the test sample. HBP

characteristically produces bacterial urease, an enzyme that catalyzes the hydrolysis of urea [( H₂)₂CO] into carbon dioxide (C0₂) 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) ₂1 ⁺ (aq) + Cl^"(aq)

This results in a loss of silver chloride by dissolution into the test sample. This loss of silver chloride is 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 (hereinafter, HBP sensor 100) comprising a chemical field-effect transistor 10

(hereinafter, ChemFET 10), in accordance with aspects of the present technique. As mentioned above, the presence of HBP is analyzed by determining an extent of ammonia present in the test sample.

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. The phrase "analyzing the test sample for presence of Helicobacter pylori" means analyzing the test sample to determine or to detect a presence of HBP and may optionally include quantifying HBP in the test sample.

The "test sample", as used herein, means and includes an in vivo sample or in vitro sample. For probing the test sample 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 endoscopy capsule, a biopsy catheter, so on and so forth. An example of the test sample, 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 in vitro, the test sample 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, in vitro, may also include test sample prepared with additives such as a suitable test buffer or water for dilution.

The phrase "extent of ammonia", as used herein means, the absence 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, may include the quantitative assessment of the ammonia present.

Now referring to FIG 1, the HBP sensor 100 includes at least one ChemFET 10. The ChemFET 10 has a body terminal 20 formed of a semiconductor substrate 12, for example silicon, having a doping polarity, either p-type or n-type. Formed within the semiconductor substrate 12 are two spaced-apart diffusion regions 30, 40 located at a surface 14 of the semiconductor substrate 12. The two spaced-apart diffusion regions 30, 40 have a doping polarity opposite to the doping polarity of the semiconductor substrate 12. Thus, when the doping polarity of the semiconductor substrate 12 is p-type, then the doping polarity of each of the two spaced-apart diffusion regions 30, 40 is n-type. Alternatively, when the doping polarity of the semiconductor substrate 12 is n-type, then the doping polarity of each of the two spaced-apart diffusion regions 30, 40 is p-type. The construction of the semiconductor substrate 12 and the two spaced-apart diffusion regions 30, 40 and effect of doping with p-type and n-type and related excesses of holes and electrons are well known in the art of semiconductors, in particular in art of MOSFETs and ChemFETs and thus has not been described herein for sake of brevity. For the purposes of explaining the present technique, hereinafter the semiconductor substrate 12 is considered to have p-type polarity and thus, the two spaced-apart diffusion regions 30, 40 are considered to have n-type polarity.

However, it may be appreciated by one skilled in the art that the polarities of the semiconductor substrate 12 and the two spaced-apart diffusion regions 30, 40 may be n-type and p- type, respectively, and such construction of the ChemFET 10 is also easily used for the purposes of the present

technique .

In the ChemFET 10 constructed with the body terminal 10 in the p-type semiconductor substrate 12, one of the n-type diffusion regions is a source terminal (in case of FIG 1 and associated description it is region 30) and the other is a drain terminal (in case of FIG 1 and associated description it is region 40) . In the ChemFET 10, an electrically

insulating stratum 50 overlies or covers at least the surface 14 of the semiconductor substrate 12 lying between the source terminal 30 (hereinafter, source 30) and the drain terminal 40 (hereinafter, drain 40). The electrically insulating stratum 50 may be formed of an electrically insulting

material, for example silicon dioxide or silicon

dioxide/silicon nitrate sandwich. The electrically insulating stratum 50 may be applied on the surface 14 of the

semiconductor substrate 12 by a variety of techniques such as thermally growing, painting, printing, etc. The ChemFET 10 also includes a gate terminal 60 (hereinafter, gate 60) . The gate 60 is a layer 62 having silver. The layer 62 overlies the electrically insulating stratum 50 such that the gate 60 i.e. the layer 62 is electrically insulated by the electrically insulating stratum 50 from the surface 14 of the semiconductor substrate 12. Thus, a potential at the gate 60 has an effect on a flow of current between the source 30 and the drain 40, referred to as a source-drain current. For example, with the p-type semiconductor substrate 12 and re^¬ type source 30 and n-type drain 40, when the gate 60 is made positive with respect to the source 30, the holes in the semiconductor substrate 12 are repelled away from a region 16 of the semiconductor substrate 12 lying in proximity of the gate 60, in case of FIG 1 the region 16 lying beneath the layer 62. Simultaneously, the electrons in the semiconductor substrate 12 are attracted towards or into the region 16.

This results in formation of a conducting channel (not shown) through the region 16 between the source 30 and the drain 40. Through the conducting channel in the region 16 a current can be made to flow by providing a potential difference between the source 30 and the drain 40. The conductance of the conducting channel, and thus, the magnitude of the source- drain current change with the potential of the gate 60 i.e. the potential of the layer 62. In one embodiment of the HBP sensor 100, the layer 62 is formed of simply silver element. In this case, the layer 62 needs to be functionalized by conversion of at least some of the silver in the layer 62 to silver chloride. This can be achieved either by reacting it with chloride ion, for example by dipping or spraying the layer 62 having silver element with hydrochloric acid. The functionalization of the layer 62 in this embodiment may be achieved either before the test sample is contacted with the ChemFET 10 or during the contact of the test sample with the ChemFET 10, if chloride ions are available in the test sample. If the test sample is gastric juice, in vivo or in vitro, it contains hydrochloric acid which helps to functionalize the layer 62.

In another embodiment of the HBP sensor 100, the layer 62 is at least partially formed of silver chloride. This will reduce the need to functionalize the layer 62, as

functionalization is only required for elemental silver in the layer 62 in this embodiment. In a related embodiment of the HBP sensor 100, the layer 62 is formed completely of silver chloride. This will obviate the need to functionalize the layer 62. In another embodiment of the HBP sensor 100, the layer 62 in the ChemFET 10 is formed of a salt of silver adapted to react with ammonia to form a silver diamine complex. The example of salt of silver may be silver bromide. Referring again to FIG 1, when the layer 62, in its

functionalized form i.e. when including silver chloride or salt of silver adapted to react with ammonia to form silver diamine complex, interacts with ammonia in the test sample, the layer 62 develops a potential (electrochemical potential) in the layer 62 which in turn has an effect on the source- drain current as explained earlier. The magnitude of the potential of the layer 62 depends on whether ammonia is reacting with the layer 62 or not. The magnitude of the potential of the layer 62 also depends on the extent of reaction which is dependent on a concentration of ammonia in the test sample. Thus, on detecting the source-drain current and observing the change in the source-drain current, the extent of ammonia is determined. Furthermore, if and when the layer 62 is completely dissolved in the test sample, a sharp and sudden change in the source-drain current is observed. This sharp change in the source-drain current, resulting from a complete loss of the layer 62 at the gate 60, is a

definitive conclusion of the presence of ammonia in the test sample. Moreover, by measuring duration from contacting the test sample with the layer 62 to occurrence of the sharp and sudden change in the source-drain current and by knowing physical dimensions of the layer 62 such as a thickness of the layer 62, a rate of dissolution of the layer 62 is determined. By comparing the rate of dissolution of the layer 62 in the test sample to a reference such as a standard curve representing relation between different ammonia

concentrations and related rate of dissolutions of a similar standard layer of silver chloride, 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.

Referring to FIG 2, the HBP sensor 100, in one exemplary embodiment, further includes a reference electrode 64. The reference electrode 64 is connected in circuit relationship with the source 30 and the drain 40 through a potential source 70 i.e. an electrical voltage source 70. As a result, a reference potential is created and added to the potential generated in the layer 62. The reference electrode 64 is formed of a material inert to ammonia and/or hydrochloric acid, such as Gold (Au) , Platinum (Pt) , and so on and so forth. The reference electrode 64 is in electrical contact with the layer 62. In the circuit is another voltage source 72 provided between the source 30 and the drain 40 to establish the potential difference sufficient enough to cause a flow of the source-drain current through the conducting channel formed in the region 16. Furthermore, a measuring device 74 such as an ammeter 74 is coupled to the circuit to measure the source-drain current.

FIG 3 is a schematic representation of another exemplary embodiment of the HBP sensor 100, and as depicted in FIG 3, in one embodiment the HBP sensor 100 includes a plurality of the chemical field-effect transistors 10. The plurality includes at least a first chemical field-effect transistor 10a (hereinafter, the first ChemFET 10a) and a second

chemical field-effect transistor 10b (hereinafter, the second ChemFET 10b) . A thickness 65 of the layer 62 in the first ChemFET 10a is different from a thickness 66 of the layer 62 in the second ChemFET 10b. Thus, the sharp and sudden change in the source drain current is observable at different durations after exposing the layers 62 of the first and the second ChemFETs 10a, 10b to the test sample. This helps in increasing the accuracy and sensitivity of the HBP sensor 100 by providing multiple measurements of the extent of ammonia in the test sample. Furthermore, when being used in vivo, the HBP sensor 100 may be used at one location in the GI tract or may be moved to make measurements of change of the source- drain current at multiple locations in the GI tract and the

HBP sensor 100 with the plurality of the ChemFETs 10a, 10b is capable of measuring the source-drain currents for a wider range of ammonia concentrations which may be present at different location of the GI tract.

In another embodiment of the HBP sensor 100, as depicted in FIG 3, at least an ion-sensitive field-effect transistor 80 (hereinafter, the ISFET 80) is present. The ISFET 80 is used to measure a pH of the test sample. Since, the rate of reaction between the layer 62 and ammonia, if present in the test sample, is dependent on the pH of the test sample, by knowing the pH of the test sample, accuracy of the

determination of the extent of ammonia in the test sample is increased. By comparing the rate of dissolution of the layer 62 in the test sample at a pH so measured using the ISFET 80 to a reference such as a standard curve representing relation between different ammonia concentrations and related rate of dissolutions of a similar standard layer of silver chloride at a pH similar to the pH so measured by the ISFET 80, 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.

As seen in FIG 3, the HBP sensor 100 further includes a housing 90 for protecting the one or more ChemFETs 10, for example the first and the second ChemFETs 10a, 10b. The one or more ChemFETs 10, for example the first and the second ChemFETs 10a, 10b are positioned inside the housing 90 such that the ChemFETs 10, except the layer 62 of the ChemFETs 10 is hermetically sealed from the test sample. Thus, the housing 90 is used to seal off the ChemFETs 10, for example the first and the second ChemFET 10a, 10b as shown in FIG 3, from the test sample when the HBP sensor 100 is used with the test sample, in vitro or in vivo. The housing 90 is made of a material inert to the test sample to be analyzed. In general for suitability of the HBP sensor 100 to be used in vivo, the housing 90 is preferably made of a material inert to gastric juice of the test subject in general, or inert to ammonia and/or hydrochloric acid concentration ranges expected to be present in the test sample. Examples of the material used to make the housing 90, may be, but not limited to, plastics, inert polymers, and so on and so forth.

As seen in FIG 3, the ISFET 80 may also be positioned inside the housing 90 such that the ISFET 80, except a part (not shown) of the ISFET 80 required for contacting the test sample, is hermetically sealed from the test sample. Furthermore, in one embodiment of the HBP sensor 100, the material of the housing 90 besides being inert to ammonia and/or hydrochloric acid is also electrically insulating. Examples of electrically insulating material may be, but not limited to, glass, Teflon, rubber-like polymers, plastics, and so on and so forth.

FIG 3 depicts an exemplary embodiment of the HBP sensor 100 having a plurality of the ChemFETs 10, namely the first and the second ChemFET 10a, 10b and the ISFET 80 positioned inside the housing 90. The housing 90 includes an aperture 68 adapted to be operable to be in an open state or in a closed state. When the HBP sensor 100 is in use with the test sample, the aperture 68 in the open state allows the test sample to contact the layer 62 of the ChemFET 10. Similarly, the aperture 68 in the closed state prevents the test sample to contact the layer 62 of the ChemFET 10. In one embodiment of the HBP sensor 100, when there are multiple ChemFETs 10a, 10b, each of the ChemFETs 10a, 10b has a distinct and

dedicated aperture which is independently operable to be in the open or in the closed state or to switch between the open and the closed states. In an alternate embodiment of the HBP sensor 100, when there are multiple ChemFETs 10a, 10b, each of the ChemFETs 10a, 10b has a distinct and dedicated

aperture which is are simultaneously operable to be in the open or in the closed state or to switch between the open and the closed states simultaneously.

The achievement of the open or the closed state of the aperture 68 is implementable by a variety of mechanisms, for example by using a flap 92 hinged (not shown) on one side of the aperture 68 and which transfers the aperture 68 between the closed state and the open state by rotation of the flap 92 around the hinge. Other mechanisms may include sliding flaps, shutter mechanism, and so on and so forth. The present technique also manifests in form of a method 1000 for analyzing a test sample of a test subject for presence of HBP, as depicted in the flow chart of FIG 4, which has been explained hereinafter in combination with FIGs 1 to 3. In the method 1000, in a step 500 the HBP sensor 100, as described in relation to any of FIGs 1 to 3, is provided. Thereafter, in a step 520, the test sample to be analyzed is contacted with the layer 62 of the gate 60. Subsequently, in a step 540, the change in the source-drain electric current is measured. Finally, in a step 560, the extent of ammonia present in the test sample is determined from the change in the source-drain electric current so measured. As explained hereinabove, the extent of ammonia present in the test sample is indicative of presence of Helicobacter pylori in the test sample.

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

1. A Helicobacter pylori sensor (100) for analyzing a test sample of a test subject for presence of Helicobacter pylori by determining an extent of ammonia present in the test sample, the Helicobacter pylori sensor (100) comprising at least one chemical field-effect transistor (10) having:

- a body terminal (20) formed of a semiconductor substrate (12) having a doping polarity;

- a source terminal (30) and a drain terminal (40) formed within the semiconductor substrate (12), wherein the source terminal (30) and the drain terminal (40) are a pair of spaced apart diffusion regions located at a surface (14) of the semiconductor substrate (12) and having a doping polarity opposite to the doping polarity of the semiconductor

substrate ( 12 ) ;

- an electrically insulating stratum (50) overlying at least the surface (14) of the semiconductor substrate (12) lying between the source terminal (30) and the drain terminal (40); and

- a gate terminal (60), wherein the gate terminal (60) is a layer (62) comprising silver and overlying the electrically insulating stratum (50) such that the gate terminal (60) is electrically insulated by the electrically insulating stratum (50) from the surface (14) of the semiconductor substrate ( 12 ) ; and

wherein the layer (62) is adapted to contact the test sample to generate a potential in the layer (62), and wherein, on contacting the layer (62) with the test sample, the extent of ammonia present in the test sample is determinable by

measuring a change in a source-drain electrical current.

2. The Helicobacter pylori sensor (100) according to claim 1, wherein the layer (62) of the gate terminal (60) comprises silver chloride.

3. The Helicobacter pylori sensor (100) according to claim 1 or 2, further comprising a reference electrode (64) connected in circuit relationship with the source terminal (30) and the drain terminal (40) through a potential source (70) such that a reference potential is created and added to the potential generated in the layer (62) .

4. The Helicobacter pylori sensor (100) according to claim 3, wherein the reference electrode (64) is formed of a material inert to ammonia and/or hydrochloric acid.

5. The Helicobacter pylori sensor (100) according to any of claims 1 to 4, comprising a plurality of the chemical field- effect transistors (10) wherein the plurality comprises at least a first chemical field-effect transistor (10a) and a second chemical field-effect transistor (10b) and wherein a thickness (65) of the layer (62) in the first chemical field- effect transistor (10a) is different from a thickness (66) of the layer (62) in the second chemical field-effect transistor (10b) .

6. The Helicobacter pylori sensor (100) according to any of claims 1 to 5, further comprising at least an ion-sensitive field-effect transistor (80) for measuring a pH of the test sample .

7. The Helicobacter pylori sensor (100) according to any of claims 1 to 6, further comprising a housing (90) for

protecting the at least one chemical field-effect transistor (10), wherein the chemical field-effect transistor (10) is positioned inside the housing (90) such that the chemical field-effect transistor (10) except the layer (62) of the chemical field-effect transistor (10) is hermetically sealed from the test sample.

8. The Helicobacter pylori sensor (100) according to claim 7, wherein the housing (90) is made of a material inert to the test sample to be analyzed with respect to ammonia and/or hydrochloric acid.

9. The Helicobacter pylori sensor (100) according to claims 7 or 8, wherein the housing (90) is made of an electrically insulating material.

10. The Helicobacter pylori sensor (100) according to any of claims 7 to 9, wherein the housing (90) comprises an aperture (68) adapted to be operable to be in an open state or in a closed state such that, when the Helicobacter pylori sensor (100) is in use with the test sample, the aperture (68) in the open state allows the test sample to contact the layer (62) of the chemical field-effect transistor (10) and the aperture (68) in the closed state prevents the test sample to contact the layer (62) of the chemical field-effect

transistor (10).

11. A method (1000) for analyzing a test sample of a test subject for presence of Helicobacter pylori, the method

(1000) comprising:

- providing (500) a Helicobacter pylori sensor (100)

according to any of claims 1 to 10;

- contacting (520) the test sample to be analyzed with the layer (62) of the gate terminal (60);

- measuring (540) the change in the source-drain electric current; and

- determining (560) the extent of ammonia present in the test sample from the change in the source-drain electric current so measured;

wherein, the extent of ammonia present in the test sample is indicative of presence of Helicobacter pylori in the test sample.