WO2022175906A1

WO2022175906A1 - Edible electronic device for patient diagnostics

Info

Publication number: WO2022175906A1
Application number: PCT/IB2022/051509
Authority: WO
Inventors: Sanjiv Sambandan; Atanu Mohanty; Manoj Varma; Ganapathy Saravanavel; Sivacharana Goud; Gunashekar K.R.
Original assignee: Indian Institute Of Science
Priority date: 2021-02-19
Filing date: 2022-02-21
Publication date: 2022-08-25
Also published as: IN202141007011A

Abstract

The present disclosure provides an edible electronic device for diagnostics of a patient. The edible electronic device communicates an external transceiver unit worn on the body of the patient or in close proximity of the patient. The edible electronic device slowly disintegrates in the patient's body and senses desired clinical parameters. The edible electronic device communicates the clinical parameters to the external transceiver unit. The external transceiver unit transmits the clinical parameters to an external device. The edible electronic device comprises a battery, a sensor, a signal modulation unit, and a communication unit, all built using edible materials. The edible electronic device is therefore safely digested and eliminated by the patient. The edible electronic device is safe to use without medical intervention.

Description

EDIBLE ELECTRONIC DEVICE FOR PATIENT DIAGNOSTICS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of priority to Indian Provisional Application No. 202141007011, filed on February 19, 2021, the contents of which are hereby incorporated by reference herein in their entirety.

TECHNICAL FIELD

[0002] The present disclosure generally relates to electronic devices. More particularly, the present disclosure relates to edible/digestible compositions that work as an electronic device inside a patient’s body for diagnosis of one or more parameters and are digested/eliminated from the patient’s body after certain time.

BACKGROUND

[0003] Electronic devices are used extensively to provide medications or perform medical procedures to patients. Medical procedures are of two types comprising non-invasive procedure and invasive procedure. The invasive procedure involves insertion of a medical device into the body of the patient. Examples include endoscopy, biopsy, and the like. The non-invasive procedure involves providing the medication by application of the medical device onto skin of the patient. Examples include wearable devices such as devices for measurements of temperature, pulse, pressure.

[0004] Several medical conditions result in a change in analyte concentrations inside the body. Examples of such conditions and corresponding analyte are acidity causing variation in H+ ions and read by pH measurements, viral loads, bleeding, infections observed by analysis of stool samples, and the like. With regards to the diagnosis of such medical conditions, invasive procedure has several advantages such as reliability, increased accuracy, and timely detection. The invasive procedures have the advantage of increased accuracy, since analyte concentrations are much larger inside the body of the patient. The disadvantage of the invasive procedures is that the invasive procedures are not easy to perform and need a medical expert to conduct them. On the other hand, the non-invasive procedures have several advantages such as ease of use and can be unsupervised. A process that does not require supervision saves the precious resource of medical professionals. However, the non-invasive procedure cannot be used to accurately diagnose medical conditions that show up as variations in analyte concentrations inside the body. Hence, there is a requirement for an invasive procedure which is both easy and safe to use without medical supervision, while at the same time being timely and reliable due to it being invasive.

[0005] With focus on the gastro-intestinal tract, the present disclosure provides a digestible electronic device that contains sensors and electronics built of materials that are safe to consume (well below toxicity limits) thereby making the device edible and/or digestible. The digestible electronic device, when swallowed by the patient, senses clinically important parameters and relays that information to the outside world wirelessly after which it is safely digested and eliminated from the patient’s body.

[0006] Existing ingestible electronic pills include capsule endoscopy. However, the existing electronic pills require medical supervision as the electronic pills need to be safely removed from the body after use. The digestible electronic devices of the present disclosure are digested and eliminated from the patient’s body by the patient’s digestive system.

SUMMARY OF THE DISCLOSURE

[0007] The present disclosure provides an edible electronic device for diagnosis of a patient. The edible electronic device is in communication with an external transceiver unit, e.g., a wearable device worn on a body of a patient. The edible electronic device performs diagnostics in the body of the patient by sensing clinical parameters and communicates the clinical parameters to the external transceiver unit. The edible electronic device comprises one or more components. The one or more components include a battery, LC (inductor-capacitor) oscillator, transistors, capacitors, sensors, a signal processing unit, and a communication unit. All the components of the edible electronic device are made of edible, biocompatible and non-toxic materials. The edible electronic device can be safely digested by the patient.

[0008] Provided herein is an edible electronic device comprising at least one of each of the following components: a battery; a sensor; a signal modulation unit connected to the battery and the sensor; and a communication unit connected to the battery and the signal modulation unit. The battery provides power to the components of the edible electronic device. The sensor senses the desired parameter in the patient’s body and sends this information to the signal modulation unit. The signal modulation unit converts the sensor output into an output signal having various frequency components and sends this output signal to the communication unit. The communication unit sends the output signal to the external transceiver unit. [0009] The present disclosure also provides an electronic diagnostic system comprising the edible electronic device and the external transceiver unit/wearable device.

[0010] The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figures 1 illustrates an edible electronic device according to one embodiment of the present disclosure.

[0012] Figures 2 illustrates an edible electronic device according to another embodiment of the present disclosure.

[0013] Figures 3 illustrates an edible electronic device according to yet another embodiment of the present disclosure.

[0014] Figure 4 shows an electrolyte embedded in a solid carrier (panel A) and copper and zinc fdms deposited on the solid electrolyte (panel B) to prepare a battery according to one embodiment.

[0015] Figure 5 shows an empty gelatin capsule (panel A) and a sugarin-coated gelatin capsule (panel B) as a housing of a battery according to one embodiment.

[0016] Figure 6 shows a battery prepared according to one embodiment. Panel A shows a gelatin capsule containing liquid isomalt. Panel B shows zinc and copper electrodes connected with silver terminals inserted into the solidified isomalt. Panel C shows the gelatin capsule of panel B where a liquid electrolyte is contained in wells built into solid isomalt. Panel D shows the voltage provided by this battery.

[0017] Figure 7 shows a schematic of an enzymatic fuel cell that can be used a battery according to one embodiment.

[0018] Figure 8 shows a two-dimensional silver coil as an edible inductor according to one embodiment. Panel A shows the two-dimensional silver coil fabricated on an isomalt substrate. Panel B shows an impedance spectrum Z_L (to) of the inductor coil shown in panel A. Panel C shows phase arg[Z_L (to)] of the inductor coil as a function of frequency.

[0019] Figure 9 shows fabrication and characteristics of a three-dimensional (3D) edible inductor coil according to one embodiment. Panel A shows spooling of liquid isomalt using a glass rod to prepare a 3D coil. Panel B shows sculpted 3D isomalt coil obtained after cooling of liquid isomalt. Panel C shows deposition of silver on the 3D-sculpted isomalt coil. Panel D shows an impedance spectrum Z_L (to) of the inductor coil shown in panel A. Panel E shows phase arg[Z_L (to)] of the inductor coil as a function of frequency.

[0020] Figure 10 shows fabrication and characteristics of a three-dimensional (3D) edible inductor coil according to another embodiment. Panel A shows liquid isomalt mixed with iron particles being poured in a cylindrical mould to obtain a ferrite isomalt core. Panel B shows the ferrite isomalt core sticking to a magnet. Panel C shows silver coil deposited on the ferrite isomalt core. Panel D shows an impedance spectrum Z_L (to) of the inductor coil shown in panel A. Panel E shows phase arg[Z_L (to)] of the inductor coil as a function of frequency.

[0021] Figure 11 shows inductances (panel A) and resistances (panel B) of the two- dimensional silver inductor coil, the three-dimensional silver-coated isomalt-coil inductor, and the three-dimensional silver coil with the ferrite core inductor.

[0022] Figure 12 shows an exemplary embodiment of signal transmission using the LC oscillators.

[0023] Figure 13 shows exemplary embodiments of capacitors.

[0024] Figure 14 shows exemplary embodiments of transistors.

[0025] Figure 15 shows exemplary embodiments of resistors.

[0026] Figure 16 shows a schematic of signal modulation according to the present disclosure. [0027] Figure 17 shows exemplary embodiments of diodes.

[0028] Figure 18 shows a signal modulation circuit according to one embodiment and the current-voltage characteristic curves of the diode. [0029] Figure 19 shows a schematic of an exemplary electronic diagnostic system according to the present disclosure.

[0030] Figure 20 shows one embodiment of an external transceiver unit according to the present disclosure.

[0031] Figure 21 shows a battery assembled using a solid electrolyte according to one embodiment.

[0032] Figure 22 shows the load characteristics of a unit cell (panel A) and two unit cells connected in series (panel B) and in parallel (panel C).

[0033] Figure 23 shows a battery assembled according to one embodiment of the present disclosure.

[0034] Figure 24A shows preparation of an isomalt substrate.

[0035] Figure 24B shows an isomalt wafer prepared according to one embodiment.

[0036] Figure 24C shows the FTIR spectra of an isomalt substrate.

[0037] Figure 24D shows dissolution of the isomalt substrate.

[0038] Figure 24E shows preparation of isomalt-sugarin-metal substrate and its dissolution in water and acid.

[0039] Figure 25 shows characteristics of the isomalt substrate.

[0040] The figures depict embodiments of the disclosure for purposes of illustration only. One skilled in the art will readily recognize from the following description that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles of the disclosure described herein.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0041] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results. Throughout this specification, the word “comprise”, or variations such as “comprises” or “comprising” or “containing” or “has” or “having”, or “including but not limited to” wherever used, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0042] Reference throughout this specification to “one embodiment”, “an embodiment”, or “some embodiments” means that a particular feature, structure or characteristic described in connection with the embodiment may be included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases “in one embodiment”, “in an embodiment”, or “in some embodiments” in various places throughout this specification may not necessarily all refer to the same embodiment. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.

Edible Electronic Device

[0043] The present disclosure provides an edible electronic device comprising sensors and electronics, all of which are made of edible food-grade materials. The edible electronic device can be swallowed or ingested by a patient after which it starts getting digested in the patient’s gastro-intestinal (GI) track. The disintegration of the outer coating of the device in the GI track slowly starts exposing the one or more sensors in the device. The sensors sense the desired parameters in the patient’s body and send this information in the form of a sensed output to the electronic components of the device where the sensor output is converted into a signal. This signal is sent to a unit outside the patient’s body which performs an analysis of the received signal, for example, the analysis of the frequency components and the power spectrum, extracts information of the sensed parameters from the analysis, in some cases stores the information in a memory and may display the information. Communication between the external unit and the edible electronic device could also permit the external unit to identify and track the location of the edible device. [0044] The edible electronic device comprises at least one of each of the following components: a battery; a sensor; a signal modulation unit connected to the battery and the sensor; and a communication unit connected to the battery and the signal modulation unit. All four components - the battery, the sensor, the signal modulation unit (SMU), and the communication unit - are built using edible materials. The term “edible” as used herein refers to components/materials that are safe to eat with some or all of the materials being digested by the body. Certain components of the edible electronic device comprise metals such as silver, gold, aluminium, iron, copper, zinc, and the like; however, the amounts of these metals used to build the components is well below the threshold limits set by government mandated food safety regulations.

[0045] The edible electronic device has an orally ingestible size and shape, i.e., the size and the shape of the edible electronic device is such that a patient can easily swallow or ingest the device. In some embodiments, the edible electronic device is in the form of a pill, capsule, or a tablet.

[0046] The battery provides power to the components of the edible electronic device. The sensor senses the desired parameter in the patient’s body and sends this information (referred to herein as “sensor output”) to the signal modulation unit (SMU). The SMU converts the sensor output into an output signal having multiple frequency components and sends this output signal to the communication unit. The communication unit sends the output signal to a unit located outside the patient’s body which performs analysis of the signal, for example, the analysis of the frequency components, extracts information of the sensed parameters from the analysis, in some cases stores the information in a memory and may display the information. Communication between the external unit and the edible electronic device could also permit the external unit to identify and track the location of the device. In some embodiments, the edible electronic device comprises more than one battery, such as 1, 2, 3, 4, 5, or more batteries; more than one sensor, such as 1, 2, 3, 4, 5, or more sensors; more than one SMU, such as 1, 2, 3, 4, 5, or more SMUs; and more than one communication unit, such as 1, 2, 3, 4, 5, or more communication units. Various combinations of the number of batteries, sensors, SMUs, and communication units are possible. For example, in one embodiment, the edible electronic device can comprise one battery, one sensor, one SMU, and one communication unit. In another embodiment, the edible electronic device can comprise one battery, 2 or more sensors, 2 or more SMUs, and one communication unit. In yet another embodiment, the edible electronic device can comprise two or more batteries, 3 or more sensors, 2 or more SMUs, and two or more communication units.

[0047] Figure 1 illustrates an exemplary embodiment of the edible electronic device. In this embodiment, the battery, the SMU, and the communication unit are enclosed in a housing and the sensor is located outside the housing.

[0048] Figure 2 illustrates another exemplary embodiment of the edible electronic device. In this embodiment, the battery, the SMU, and the communication unit are enclosed in a housing; the sensor is located outside the housing; and a slow-release coating is provided surrounding the housing that covers the housing and the sensor. The term “surrounding the housing” means the housing is partially or completely covered or coated by the slow-release coating. The slow- release coating permits the control of the timing of the exposure of the sensor to the environment.

[0049] Figure 3 illustrates yet another exemplary embodiment of the edible electronic device. In this embodiment, the battery, the SMU, and the communication unit are enclosed in a housing; the sensors are located outside the housing; and a slow-release coating of varying thickness is provided surrounding the housing that covers the housing and the sensors. If sensor 1 needs to be exposed first and sensor 2 needs to be exposed second, then the slow-release coating of varying thickness can be provided where the thickness of the coating on sensor 1 is smaller and the thickness of the coating on sensor 2 is bigger. Since the coating on sensor 1 is smaller in thickness, it will disintegrate sooner than the coating on sensor 2 thereby exposing sensor 1 before sensor 2. Thus, by employing a slow-release coating and by varying the thickness of the coating, the exposure of the sensors can be timed. The slow-release coating can also be employed to coat other components of the edible electronic device to time the exposure of the component to other components and/or the surrounding.

[0050] Although Figures 1-3 show a single battery, a single SMU, one or more sensors, and a single communication unit, the edible electronic device can include more than one of each of these components. The arrangement of multiple components and their connections are within the skill of an ordinary artisan in the field of electronics. [0051] In some embodiments, the housing comprising the battery, the SMU, and the communication unit inside and the sensor on the outside, is selected from gelatin, cellulose such as ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose (HPMC), starch, sugarin or a combination thereof. In an exemplary embodiment, the housing is comprised of gelatin.

[0052] In some embodiments, the slow-release coating is comprised of sugarin. In some embodiments, the slow-release coating is comprised of isomalt and sugarin. In some embodiments, the slow-release coating is comprised of isomalt, sugarin, cellulose such as ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose (HPMC), or a combination thereof. In some embodiments, the slow-release coating is employed to time the exposure of one or more components of the edible electronic device. In some embodiments, the slow- release coating is employed to protect one or more components from moisture, acidic pH of the stomach, or any other environmental variations. In some embodiments, the slow-release coating extends the exposure of the one or more components by about 10 minutes, 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours or up to about 6 hours.

Battery

[0053] In some embodiments, the battery of the edible electronic device comprises an electrolyte, a cathode, an anode, a terminal connected to the cathode and a terminal connected to the anode. Every component of the battery is edible and well below the toxicity levels set forth food safety regulations.

[0054] In some embodiments, the battery is a galvanic cell or a voltaic cell. A voltaic cell or a galvanic cell is an electrochemical cell in which an electric current is generated from the spontaneous redox reactions. Anodes and cathodes employed in voltaic cells are known in the art. In the galvanic cell, a metal or a chemical species with a higher reduction potential serves as a cathode and a metal or a chemical species with a lower reduction potential serves as an anode. Table 1 shows standard reduction potentials of some metals and chemical species. Table 1

[0055] As one can see from Table 1 above, standard reduction potentials of metals and chemical species are known in the art. Accordingly, one of ordinary skill in the art can select a metal/ionic species with a higher reduction potential as a cathode and a metal/ionic species with a lower reduction potential as an anode. For example, copper has a higher reduction potential than zinc (see Table 1). Accordingly, in one embodiment of the edible electronic device, the cathode comprises copper and the anode comprises zinc. However, as one can see from Table 1, the reduction potential of zinc is higher than that of aluminium, magnesium, and sodium. Therefore, in some embodiments, the cathode can comprise zinc and the anode can comprise aluminium, magnesium.

[0056] In exemplary embodiments, the anode is selected from nickel, cadmium, iron, zinc, aluminium, magnesium, or sodium. In exemplary embodiments, the cathode is selected from copper, silver, manganese, or iron. However, as explained above, what serves as a cathode and an anode depends on the reduction potential of the chemical entity. That is, the same chemical entity can serve as anode in one embodiment (when paired with an entity with a higher reduction potential as cathode) and as cathode in another embodiment (when paired with an entity with a lower reduction potential as anode). Accordingly, in some embodiments, the anode and the cathode of the battery of the edible electronic device are selected from nickel, iron, zinc, aluminium, magnesium, sodium, copper, silver, and depending on the reduction potential of these chemical entities. The quantities of the metals employed to form the cathode and the anode are well below the toxicity limits of these metals. Table 2 below shows toxicity level limits of some of the metals for a 10kg child/day. The amounts of metals used (the middle column of Table 2) to prepare one or more components of the edible electronic device are far less than the toxicity level limits such as those shown in Table 2.

Table 2

[0057] The anode and the cathode can be in the form of a thin film or a thin wire. The thickness of the film can be in the submicron ranges such as for example, about 10-200 nm or about 50 100 nm including values and ranges thereof. Thin films of metals can be deposited using techniques known in the art such as physical vapor deposition, thermal vapor deposition, DC magnetron sputtering and the like. The thickness of the film or the length and the diameter of the wire are selected to make sure that the total amount of the component employed in the entire edible electronic device is below the toxicity limit.

[0058] In an exemplary embodiment, the terminal connected to the cathode and the terminal connected to the anode (“battery terminals”) comprise silver. However, the terminals can comprise edible conductors other than silver such as copper, zinc and the like. The terminals can be in the form of a thin wire.

[0059] In some embodiments, the electrolyte is selected from the group consisting of lemon extract, orange extract, a potato extract, gastric juice, citric acid, malic acid, tartaric acid, oxalic acid, fumaric acid, succinic acid and a combination thereof. In an exemplary embodiment, the lemon extract is lemon juice. In an exemplary embodiment, the orange extract is orange juice. [0060] The electrolyte, the anode and the cathode and the battery terminals are held by a carrier. In some embodiments, the carrier is a solid. In some embodiments, the carrier is a gel. In some embodiments, the carrier is selected from pectin, gelatin, isomalt, sugarin, sugar paper, or a combination thereof

[0061] In one embodiment, the electrolyte and the carrier are mixed to prepare a solid electrolyte. For example, in one embodiment, a lemon extract, orange extract, citric acid, or any other electrolyte is heated; a solid substrate like pectin or gelatin is added; and the mixture is allowed to cool down and solidify on a surface such as a sheet of polydimethylsiloxane (PDMS) or any other substrate to provide support. After cooling, the solidified substrate is lifted off the surface and is free standing. In this embodiment, the solidified mixture of the electrolyte mixed with a carrier such as pectin/gelatin is a solid electrolyte. In some embodiments, a thin sheet of metal electrodes, e.g., copper and zinc, are placed on either side of the solid electrolyte as a cathode and anode and thin wires of conductor metal, e.g., silver, are connected to the electrodes as terminals. This assembly cathode and anode placed on either side of the solid electrolyte and connected to respective terminals acts as a battery.

[0062] In another embodiment, a cathode and an anode can be deposited in the form of a thin film on the surface of a solid electrolyte. An exemplary embodiment is shown in Figure 4. Metal terminals can be added to the electrode films. This assembly can act as a battery. Alternatively, first a thin film of electrodes can be coated/deposited on the surface of an edible substrate such as gelatin, cellulose or isomalt and then an electrolyte-carrier mixture can be allowed to solidify on the thin films of electrodes. Battery terminals can be connected to the electrodes. This assembly can act as a battery.

[0063] In yet another embodiment, the electrolyte is supported in a soft carrier such as a gel. In an exemplary embodiment, a gelatin capsule is employed as a body/housing of the battery (Figure 5, panel A). Gelatin could be sensitive to strong electrolytes and moisture. Therefore, in some embodiments, the gelatin capsule is coated from inside with a coating comprising sugarin (Figure 5, panel B). Sugarin is apurely edible substance and is used in jams, jellies and cake decors. The coating of sugarin makes the gelatin capsule resistant to moisture and electrolytes. To the sugarin-coated gelatin capsule, a further carrier such as isomalt can be added to hold the electrolyte. In one embodiment, isomalt is heated to obtain liquid isomalt and a desired amount of liquid isomalt is poured into the sugarin-coated gelatin capsule; an object of desired shape/size can be inserted into the liquid isomalt to obtain a well of desired size/shape. The liquid isomalt is allowed to cool down to form a gel; and the object is removed to obtain a well in the isomalt. The electrolyte is added to this isomalt well and the electrodes are inserted into the electrolyte.

[0064] In another embodiment, the electrolyte can be sandwiched between the layers of a soft/gel-like carrier. In an exemplary embodiment, liquid isomalt is poured into a housing/body of the battery, such as a sugarin-coated gelatin capsule (Figure 6, panel A). Desired electrodes (e.g., copper and zinc) are dipped into the liquid isomalt; thin wires made of an edible conductor such as silver are connected to the electrodes as battery terminals (Figure 6, panel B). Once the isomalt is solidified, a desired amount of electrolyte is added on top of the isomalt layer. The remaining part of the gelatin capsule can be used to seal the capsule or another layer of liquid isomalt is added on top of the electrolyte and allowed to solidify. This gives a battery where the electrolyte is sandwiched between two layers of a soft/gel carrier such as isomalt (Figure 6, panel C). In an exemplary embodiment, this battery gives an output of about 0.9v (Figure 6, panel D).

[0065] While a few exemplary battery designs based on the principle of a galvanic cell are described above, the scope of the batteries encompassed by the invention is not limited to these exemplary designs. One of ordinary skill in the art can use different metals as anodes and cathodes and for battery terminals than those described in the exemplary embodiments. Similarly, one of ordinary skill in the art can use carriers, electrolytes, and battery terminals other than those described above in the exemplary embodiments.

[0066] In another embodiment, a sugar battery may be used in which the electric current is generated by oxidation of glucose. Figure 7 shows a schematic of a glucose based Enzymatic Fuel Cell (EFC). EFCs provide one of simplest means of producing power in a bio-compatible manner. Glucose is one of the most abundant metabolites in a human body. Therefore, EFCs based on the oxidation of glucose by enzyme Glucose Oxidase (GOx) are of immense value for self-powered, implantable devices. As shown in Figure 7, GOx along with its co-factors are attached to an electrode, to form the anode. The electrode could be a metal or carbon based. At the anode, GOx catalyzes the conversion of glucose into gluconic acid. Typically, two electrons are generated in the process of catalysation. Cathode is formed by attaching an oxygen reducing enzyme such as Bilrubin Oxidase (BOx) which utilizes the electrons for the reduction reaction, completing the circuit. The anode and cathode can be connected through a desired load, for example, to power the components of the edible electronic device. The advantage of the EFCs is that the EFCs are made of flexible materials. The EFCs can be fabricated on any geometries including curved surfaces. Further, improvements in synthetic biology have yielded enzymes which can operate in extreme environments such as acidic environments similar to human gut.

Sensor

[0067] The sensors of the edible electronic device sense the internal parameters of interest in the patient’s body and relay that information (“sensor output”) to the SMU. The one or more sensors are located preferably outside the housing of the edible electronic device so that they are exposed at the desired location at desired time while the other components (the battery, the SMU, and the communication unit) are still protected inside the housing and are intact to receive the sensor output. The timing of the exposure of the sensors can be modulated by providing a slow-release coating as shown in Figure 2. For example, if the sensor needs to be exposed only when the edible electronic device reaches the stomach, a slow-release coating can be provided surrounding the housing and the sensor. The thickness of the slow-release coating can be adjusted so that the coating does not disintegrate in the mouth or the food pipe of the patient but disintegrates only when the edible electronic device reaches the stomach thereby exposing the sensor. The thickness of the slow-release coating can be adjusted to time the exposure of various sensors. For example, sensor 1 can have a slow-release coating of smaller thickness while sensor 2 can have a slow-release coating of larger thickness (Figure 3) or vice versa. In this case, the slow-release coating on sensor 1 will disintegrate before that on sensor 2 thereby exposing sensor 1 before sensor 2.

[0068] Exemplary parameters sensed by the sensor include, but are not limited to, pH, internal bleeding, acidity, pathogens that cause infection (e.g., the presence of a bacteria, parasite, or the like) or a combination thereof.

[0069] In some embodiments, the sensor comprises a battery, a sensing component and one or more components selected from a resistor, capacitor, inductor, transistor, and diode wherein the analyte to be sensed changes the current voltage characteristics of the resistor, capacitor, inductor, transistor, and/or diode. The resistor, capacitor, inductor, transistor and diode maybe used singly or in combination to form a sensor circuit. Further, they may be coated with an analyte specific coating that results in the device responding to the specific analyte only. For example, in some embodiments, the sensor can be targeted to a specific location in the body by providing a suitable inorganic or organic coating, such as a coating of an oxide, an antibody, a receptor, a ligand, and the like over the components of the sensor or over the housing or slow- release coating of the edible electronic device.

[0070] The sensor has its own battery to provide power to the sensing component and to relay the sensor output to the SMU. The components and the construction of the battery is described above. In the embodiments where the sensor senses pH or acidity, the electrolytes described above may act as the sensing component, i.e., in these embodiments, the sensing component of the sensor and the electrolyte of the battery of the sensor are the same. In other embodiments, the sensing component is different from the electrolyte of the sensor’s battery.

[0071] In some embodiments, the sensor comprises a sensing component in contact with a first and a second metal, a conductor connected to the first metal and a conductor connected to the second metal. The first and the second metal serve as a cathode and anode; the conductors connected to the first and the second metal are battery terminals; and the sensing component is the electrolyte. The cathode, anode, battery terminals, the electrolyte, and their assembly are as explained above.

[0072] In some embodiments, the sensing component is different from the electrolyte. In these embodiments, the sensor comprises a sensing component, a first and a second metal in contact with an electrolyte, a conductor connected to the first metal and a conductor connected to the second metal. The first and the second metal serve as a cathode and anode and the conductors connected to the first and the second metal are battery terminals. The cathode, anode, battery terminals, the electrolyte, and their assembly are as explained above.

Signal Modulation Unit (SMU)

[0073] The SMU of the edible electronic device receives the sensor output and converts it into a signal having various frequency components. The SMU comprises a signal source, a linear device, and a non-linear device; all made of edible materials.

[0074] The signal source sends an input signal having one or more well defined frequency components into the combination of the linear device and the non-linear device. For example, a well-defined sinusoidal input signal would have one frequency component. The non-linear device is connected to the sensor and receives the sensor output. The linear device and the non linear device convert the input signal based on the sensor output into an output signal having multiple frequency components with the power spectrum being different from the input signal. It is also possible that the sensor output is such that there is no change in the input signal and the output signal has the same power spectrum as the input signal. This output signal is received by the communication unit. The shape and frequency spectrum of the output signal changes as the sensor output changes. Thus, by reading the output signal, the sensor output and thereby the value of the sensed parameter can be determined.

[0075] In some embodiments, the signal source itself generates the input signal and sends it to the linear device. In some other embodiments, the signal source receives the input signal from outside the patient’s body and sends the received signal to the linear device as the input signal.

[0076] In the embodiments where the signal source generates a sinusoidal input signal, the signal source is an oscillator (for example an LC oscillator). The structure and components of the oscillators are known in the art. The oscillator comprises an inductor and a capacitor. In some embodiments, the oscillator further comprises a transistor. One of ordinary skill in the art understands that in the oscillator, there can be more than one inductor, more than one capacitor and optionally, one or more transistors. The arrangement of the inductor, capacitor and if present, transistor, can be designed in various ways and is within the skill of a person of ordinary skill in the field of electronics. In an exemplary embodiment, the oscillator is Pierce oscillator, Colpitts oscillator, phase shift oscillator etc. The inductor, capacitor, and the transistor are all made of edible materials.

[0077] In some embodiments, the inductor comprises an edible conductor deposited on an edible substrate. The inductors can have a planar shape or a three-dimensional shape. The edible conductor can be deposited on the edible substrate in various patterns which are selected based on the frequency and the direction of the signal to be transmitted or received.

[0078] The edible conductor includes, but is not limited to, silver, copper, and the like. The edible substrate comprises isomalt, sugarin, gelatin, and a combination thereof. In an exemplary embodiment, the inductor comprises isomalt as the edible substrate and silver as the edible conductor. In another exemplary embodiment, the inductor comprises a two- dimensional coil of an edible conductor on an edible substrate, e.g., a two-dimensional silver coil on an isomalt substrate (Figure 8, panel A). In yet another embodiment, the inductor comprises a three-dimensional coil of an edible substrate coated with a layer or particles of an edible conductor, e.g., a three-dimensional isomalt coil coated with a silver layer or silver particles (Figure 9, panel C). In yet another embodiment, the inductor comprises an edible substrate embedded with particles of an edible material that increases the permeability and coated with coil of an edible conductor, e.g., an isomalt substrate embedded with iron particles (iron increases the permeability) and coated with a silver coil. An exemplary embodiment is shown in Figure 10, panel C.

[0079] Figure 12 shows an exemplary embodiment of signal transmission using the LC oscillators. In this embodiment, a transmitter LC circuit is implemented on a unit located outside the patient’s body such as a wearable patch. A receiver LC circuit is implemented on the isomalt substrate. Figure 12, upper panel, shows the circuit setup and the lower panel shows the waveforms picked up on the LC oscillator. As the distance between transmitter and receiver is varied, the output peak-peak voltage varies with closer proximity showing better reception.

[0080] Another component of the oscillator is a capacitor. In some embodiments, the capacitor comprises a first edible conductor in contact with an edible insulator in contact with a second edible conductor. The first and the second edible conductors can be deposited on the edible insulator in various shapes and patterns, for example, as a continuous thin film, as a coil, as stripes, etc. The first and the second edible conductors can be arranged in various ways to contact the edible insulator. Figure 13 shows a few exemplary arrangements of the first and the second edible conductors in contact with the edible insulator. Panels A and B of Figure 13 show a planar arrangement of the first and the second edible conductors in contact with the edible insulator. Panel C shows a cross-section of a cylindrical capacitor according to one embodiment, wherein the first edible conductor in the cylindrical form is in contact with the edible insulator in the cylindrical form which in turn is in contact with the second edible conductor in the cylindrical form. Figure 13, panels D and E show a capacitor made according to one embodiment, wherein a thin film of silver (edible conductor) is deposited on the top and the bottom side an isomalt substrate (edible insulator).

[0081] In some embodiments, the first and the second edible conductor of the capacitor is selected from aluminium, silver, or copper and the edible insulator is selected from isomalt, sugarin, albumin, cellulose, or a combination thereof. In some embodiments, the edible insulator is isomalt or isomalt coated with a slow-release coating such as sugarin. In some embodiments, the first and the second edible conductor is silver and the edible insulator is isomalt or isomalt-coated with sugarin. In some embodiments, the capacitor comprises a first layer of silver, a second layer of an isomalt or a sugarin-coated isomalt, and a third layer of silver. [0082] In some embodiments, the oscillator comprises a transistor. In some embodiments, the transistor comprises a metal connected to an insulator connected to an edible semiconductor connected a first and a second ohmic contact. Figure 14 shows exemplary arrangements of the components of the transistor according to some embodiments. In some embodiments, the transistors are built by depositing layers or films of the components according to desired arrangement patterns. The thickness of the layer or the film can be in the submicron ranges such as for example, about 10-500 nm, 10-400 nm, 10-300 nm, 10-250 nm, 10-200 nm, 10-100 nm or about 50-100 nm including values and ranges thereof. The properties of the transistor can be modulated by controlling the thickness and topology of the components.

[0083] In some embodiments of the transistor, the metal is selected from aluminium, silver, or gold; the insulator is selected from isomalt, sugarin, an oxide (e.g., SiChor a metal oxide such as MgO, ZnO, aluminium oxide, and the like), xanthan gum, sugar paper, cotton, egg albumen, gelatin, jute, or a combination thereof; the edible semiconductor is selected from zinc oxide, amorphous silicon and the like; and the first and the second ohmic contact comprise a metal of appropriate work function. The metal employed for the ohmic contact depends on the type of the semiconductor. In general, the ohmic contact is created by having a metal-semiconductor contact that can transport carriers across the junction easily. This may include having a hole transporting semiconductor made to contact a high work function metal, or electron transporting semiconductor made to contact a low work function metal or having a contact that encourages tunnelling currents. For electron transporting semiconductors, the ohmic contact comprises aluminium, calcium, magnesium and other low work function metals. For hole transporting semiconductors, the ohmic contact comprises of gold, silver, and other high workfunction metals.

[0084] For Schottky contact, the contact must encourage charge transport in one direction only. Therefore, for electron-transporting semiconductors, the Schottky contact is made of a high workfunction metal such as gold, silver etc. For hole -transporting semiconductors, the Schottky contact is made of a low workfunction metal such as aluminium, calcium, or magnesium.

[0085] In some embodiments, the transistor comprises an edible substrate to support the assembly of the metal, the insulator, the semiconductor, and the first and the second ohmic contact. In some embodiments, the edible substrate is selected from a sugar paper, isomalt, sugarin, an oxide (SiC or a metal oxide such as MgO, ZnO, aluminium oxide, and the like), xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof. [0086] The oscillator comprising the inductor, capacitor, and optionally the transistor, as described above, generates an input signal that is pushed through the combination of the linear device and the non-linear device to convert the sensor output received by the non-linear device into an output signal of different shapes with a unique power spectrum. The power spectrum of the output signal is shaped by the sensor output. It is also possible that the sensor output is such that there is no change in the input signal and the output signal has the same power spectrum as the input signal. Power spectrum is a measure of the frequency content of the signal and refers to the amplitude or power of the signal at each of the frequencies it contains.

[0087] In the embodiments where the signal source receives the signal from outside the patient’s body, the signal source can be a receiver antenna or a MEMS (micro electromechanical system) resonator. The antenna or the MEMS resonator are build using edible materials. The antenna would receive electromagnetic signals whereas the MEMS resonator would receive acoustic signals.

[0088] In some embodiments, the antenna comprises an edible conductor coated on an edible substrate. The shape and the patterns in which the edible conductor is deposited on the edible substrate can be designed in various ways depending on the frequencies and the direction of the input signal to be received. In some embodiments, the edible conductor is selected from silver, aluminium, or copper and the edible substrate is selected from isomalt, sugarin, sugar paper, gelatin, egg albumen or a combination thereof. In an exemplary embodiment of the antenna, the edible conductor is silver and the edible substrate is isomalt or isomalt comprising a sugarin coating. In another exemplary embodiment, the antenna comprises a silver coil deposited on isomalt or a sugarin-coated isomalt. For example, the inductor shown in the upper panel of Figure 8 can work as an antenna in the SMU to receive an input signal outside from the patient’s body. The input signal received by the antenna of the SMU is pushed through the combination of the linear device and the non-linear device to convert the sensor output received by the non-linear device into a signal of different shapes having a unique power spectrum. The antenna in the SMU is a receive antenna. The term “receiver antenna” as used herein means that the circuit of the antenna is configured to receive the signal. The same antenna can act as a receiver antenna or a transmitter antenna depending on how the antenna circuit is wired with respect to the other components.

[0089] In some embodiments, the signal is an acoustic signal generated outside the patient’s body. In one embodiment, the acoustic signal is in the ultrasound frequency band. In these embodiments, to receive the acoustic signal, the signal source in the SMU is a MEMS resonator comprising edible piezoelectric (e.g., sugar), SAW transducers, cantilevers, and diaphragms. The edible MEMS resonator in the SMU receives the acoustic signal (e.g., an ultrasound signal) and converts it into an Input signal which is pushed through the combination of the linear device and the non-linear device to convert the sensor output received by the non-linear device into a signal of different shapes and having a unique power spectrum (output signal). It is also possible that the sensor output is such that there is no change in the input signal and the output signal has the same power spectrum as the input signal. Power spectrum is a measure of the frequency content of the signal and refers to the amplitude or power of the signal at each of the frequencies it contains.

[0090] The input signal from the signal source is sent to the linear device. In some embodiments, the linear device comprises one or more resistors build using edible materials. In some embodiments, the resistor comprises an edible semiconductor connected to a first and a second edible ohmic contact. In some embodiments, the resistor comprises an edible insulator substrate to support the assembly of the semiconductor and the ohmic contacts. The edible semiconductor and the first and the second ohmic contacts can be arranged in various ways. Figure 15 shows exemplary arrangements of the edible semiconductor and the first and the second ohmic contacts on an edible insulator substrate to form the resistor. Panel E of Figure 15 shows a resistor comprising zinc oxide as the semiconductor, aluminium as the first and the second ohmic contacts and sugar paper as the edible insulator substrate. In some embodiments, the resistors are built by depositing layers or films of the components according to desired arrangement patterns. The thickness of the layer or the film can be in the submicron ranges such as for example, about 10-500 nm, 10-400 nm, 10-300 nm, 10-250 nm, 10-200 nm, 10-100 nm or about 50-100 nm including values and ranges thereof. The properties of the resistor can be modulated by controlling the thickness and topology of the components.

[0091] In some embodiments of the resistor, the edible semiconductor is selected from zinc oxide and amorphous silicon. As noted above, the metals employed for the ohmic contact depend on the type of the semiconductor. In general, the ohmic contact is created by having a metal-semiconductor contact that can transport carriers across the junction easily. This may include having a hole transporting semiconductor made to contact a high work function metal, or electron transporting semiconductor made to contact a low work function metal or having a contact that encourages tunnelling currents. For electron transporting semiconductors, the ohmic contact comprises aluminium, calcium, magnesium and other low work function metals. For hole-transporting semiconductors, the ohmic contact comprises of gold, silver, and other high workfunction metals. In some embodiments, the edible insulator substrate is selected from a sugar paper, isomalt, sugarin, an oxide (e.g., SiCh or a metal oxide such as MgO, ZnO, aluminium oxide, and the like), xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof.

[0092] The linear device is connected to the non-linear device. The non-linear device receives the input signal from the signal source through the linear device and also receives the sensor output from the sensor. The sensor output changes the bias voltage of the non-linear device and based on this change the non-linear device converts the input signal into a signal having different shape and a unique power spectrum. It is also possible that the sensor output is such that there is no change in the input signal and the output signal has the same power spectrum as the input signal. For example, the edible electronic device comprises a sensor that senses the pH of the stomach. If the pH of the stomach is 1, the sensor output will change the biasing of the non-linear device by certain voltage. If the pH is 2, the sensor output will change the biasing of the non-linear device by a different voltage amount. That is, the bias value of the non-linear device changes based on the sensor output. Based on this bias value, the non-linear device changes the shape of the signal and power spectrum of the input signal into something different. This is shown in Figure 16. In this Figure, the box showing “Voltage-controlled Harmonics generator” comprises the non-linear device. The Voltage-controlled Harmonics generator receives a sinusoidal signal (input signal) from the oscillator and also receives the sensor output (Vsense) from the Sensing Unit. Based on the value of Vsense, the Voltage-controlled Harmonics generator changes the shape of the sinusoidal signal into a signal having different shape (output signal) as shown in the bottom right panel of Figure 16. If the sensor output is Vsense I, the shape of the signal generated by the Voltage-controlled Harmonics generator (the non-linear device) is different from the shape of the signal when the sensor output is Vsense2.

[0093] In some embodiments, the non-linear device is a diode or a transistor or a nonlinear resistor. Every component of the diode, the transistor, and the non-linear resistor is edible. The components and the construction of the edible transistors is described above.

[0094] In some embodiments, the diode comprises an edible semiconductor connected to an edible Schottky contact and an edible ohmic contact. An edible insulator substrate is employed to support the assembly of the edible semiconductor, the Schottky contact, and the ohmic contact. The edible semiconductor, the Schottky contact and the ohmic contact can be arranged in various ways. Figure 17 shows exemplary arrangements of the edible semiconductor, the Schottky contact and the ohmic contact on an edible insulator substrate to form the diode. In some embodiments, the diodes are built by depositing layers or fdms of the components according to desired arrangements. The thickness of the layer or the fdm can be in the submicron ranges such as for example, about 10-500 nm, 10-400 nm, 10-300 nm, 10-250 nm, 10-200 nm, 10-100 nm or about 50-100 nm including values and ranges thereof. The forward and reverse current voltage (IV) characteristics of the diode can be controlled by controlling the thickness of the semiconductor and the topology of the diode.

[0095] In some embodiments of the diode, the edible semiconductor is selected from zinc oxide and amorphous silicon. For Schottky contact, the contact must encourage charge transport in one direction only. Therefore, for electron-transporting semiconductors, the Schottky contact comprises a high workfunction metal such as gold, silver etc. For hole-transporting semiconductors, the Schottky contact comprises a low workfunction metal such as aluminium, calcium, or magnesium. As noted above, the metal employed for the ohmic contact depends on the type of the semiconductor. In general, the ohmic contact is created by having a metal- semiconductor contact that can transport carriers across the junction easily. This may include having a hole transporting semiconductor made to contact a high work function metal, or electron transporting semiconductor made to contact a low work function metal or having a contact that encourages tunnelling currents. For electron transporting semiconductors, the ohmic contact comprises aluminium, calcium, magnesium and other low work function metals. For hole-transporting semiconductors, the ohmic contact comprises of gold, silver, and other high workfunction metals. In some embodiments, the edible insulator substrate is selected from a sugar paper, isomalt, sugarin, an oxide (e.g., SiC or a metal oxide such as MgO, ZnO, aluminium oxide, and the like), xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof.

[0096] A nonlinear resistor comprises a thin layer of an insulator or a semiconductor with two contacts. In some embodiments, the edible insulator is selected from a sugar paper, isomalt, sugarin, an oxide (e.g., SiCh or a metal oxide such as MgO, ZnO, aluminium oxide, and the like), xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof. In some embodiments, the edible semiconductor is selected from zinc oxide or amorphous silicon. The contacts comprise any suitable metal such as zinc, copper, aluminium, gold, silver, etc. [0097] Figure 18 shows an exemplary embodiment of a SMU and the forward and reverse current voltage (IV) characteristic curve of the non-linear device of the SMU. In this embodiment, the SMU comprises oscillators (inductors and capacitors) as an input signal source, a resistor (the linear device), and a diode (the non-linear device) comprising gold as the Schottky contact and aluminium or silver as the ohmic contact, zinc oxide as the semi conductor on a xanthan gum as edible insulator substrate. The pH sensor senses the pH of hydrochloric acid and sends the sensor output to the diode/non-linear device. According to the pH, the sensor output changes the bias voltage of the diode and the diode, in turn, changes the shape of the input signal received from the oscillator through the resistor. The signal generated by the diode/non-linear device is referred to herein as the output signal.

Communication unit

[0098] The communication unit is connected to the SMU and receives the output signal. The communication unit transmits the received signal to a unit such as a wearable or hand-held device located externally on the patient’s body. To transmit the output signal, the communication unit comprises an antenna. The structure and construction of the antenna is described above. The antenna in the communication unit acts as a transmitter antenna, i.e., the circuit of the antenna is designed to transmit the output signal. In some embodiments, the antenna may receive the output signal directly from the SMU. Alternatively, in some embodiments, an amplifier may be placed before the antenna that amplifies the output signal and the antenna receives the amplified signal. The amplifier comprises one or more components selected from a transistor, an inductor, a resistor, and a capacitor; the structure and construction of each of which is described above. Various ways of arranging these components to design amplifier circuits are known in the art.

Electronic Diagnostic System

[0099] The edible electronic device sends the output signal to a transceiver unit located outside the patient’s body. In some embodiments, the transceiver unit is attached to the patient’s body and is referred to herein as a wearable patch or wearable device. In some embodiments, the transceiver unit is located in close proximity to the patient’s body. The present disclosure provides an electronic diagnostic system comprising the edible electronic device and the external transceiver unit. [00100] Figure 19 shows an exemplary electronic diagnostic system comprising edible electronic device 101 in communication with an external transceiver unit 102 for diagnosing a patient 100. In this exemplary embodiment, the external transceiver unit is shown as a wearable device 102 worn by the patient 100. The edible electronic device 101 is swallowed by the patient 100. In some embodiments, the position of the edible electronic device 101 inside the patient’s body may be tracked by the wearable device 102; however, tracking the position of the edible electronic device at all times is an optional feature. When the edible electronic device 101 reaches a desired location, it senses a desired clinical parameter. The clinical parameters may be pH, internal bleeding, acidity, pathogen causing infection, glucose levels, and the like. The edible electronic device 101 communicates the clinical parameters with the wearable device 102. In an embodiment, a plurality of edible electronic devices may communicate with a single wearable device. In another embodiment, each of the plurality of edible electronic devices may communicate with each of a plurality of wearable devices. The edible electronic device 101 resides inside the body of the patient 100 when communicating with the wearable device 102. Hence, one of the requirements of the edible electronic device 101 is consumption of low energy. Therefore, it is desired that the external transceiver unit 102 be placed on the patient’s body as a wearable device or be located in close proximity of the patient’s body so that the distance between the edible electronic device 101 and the external transceiver unit 102 is minimal. When the distance is minimal, the edible electronic device 101 may communicate with the external transceiver unit 102 with reduced energy consumption.

[00101] In some embodiments, the external transceiver unit receives the output signal from the communication unit of the edible electronic device and transmits an electromagnetic or acoustic signal to the signal source of the SMU of the edible electronic device. As discussed above, in some embodiments, the signal source in the SMU receives the signal from outside. In these embodiments, the external transceiver unit can transmit the signal to the signal source in the SMU. In some embodiments, the signal transmitted by the external transceiver unit is an electromagnetic signal. In some embodiments, the signal transmitted by the external transceiver unit is an acoustic signal. In one embodiment, the acoustic signal is in the ultrasound frequency band.

[00102] In the embodiments where the signal source in the SMU of the edible electronic device generates its own signal through an oscillator, the external transceiver unit does not transmit a signal to the signal source in the SMU. In this embodiment, the external transceiver unit only receives the output signal from the communication unit of the edible electronic device.

[00103] In some embodiments, the external transceiver unit/wearable device 102 can be a feedback system 107 as shown in Figure 20. The feedback system 107 may comprise a sensor array 103, computing and memory 104, a battery 105, and an actuator 106. The sensor array 103 may comprise one or more sensors (these sensors are different from the sensors of the edible electronic device). For example, a temperature sensor may monitor temperature of the patient 100, a heart rate sensor may measure for pulse of the patient 100, a sweat sensor for analysis of sweating in the patient 100, and the like. The external transceiver unit/wearable device 102 may communicate measured data from its sensors and clinical parameters sensed by the edible electronic device 101 to an external device. The measured data may be stored in the memory 104. The external device may be a computing device. For example, the computing device may be a mobile device associated with the patient 100. The computing device may be a mobile device associated with a doctor. The measured data may be transmitted to a central server. The battery 105 may power the external transceiver unit/wearable device 102. The actuator 106 may be configured for targeted drug delivery, emergency medical assistance, and the like. The edible electronic device 101 is digested/eliminated by the body, upon communicating the clinical parameters.

[00104] It is to be understood that the foregoing descriptive matter is illustrative of the disclosure and not a limitation. While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. Those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein. Similarly, additional embodiments and features of the present disclosure will be apparent to one of ordinary skill in art based upon description provided herein.

[00105] Descriptions of well-known/conventional methods/steps and techniques are omitted so as to not unnecessarily obscure the embodiments herein. Further, the disclosure herein provides for examples illustrating the above-described embodiments, and in order to illustrate the embodiments of the present disclosure certain aspects have been employed. The examples used herein for such illustration are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the following examples should not be construed as limiting the scope of the embodiments herein.

EXAMPLES

Example 1: Preparation of an edible battery containing a solid electrolyte

[00106] 10 ml of lemon extract was prepared by squeezing fresh lemons and was heated up to 150°C. 0.5 g of pectin was added to the heated lemon extract, the mixture was stirred continuously for 3 min using a glass rod. The mixture was allowed to cool to the room temperature. This semi-solid mixture was used as an electrolyte. After the mixture cooled down, a small amount of it was poured onto a PDMS sheet and left overnight to the ambient conditions. The pectin-electrolyte mixture was dried by the next day (Figure 21, panel A) and had flexible properties (Figure 21, panel B). It was removed from the PDMS sheet and placed on a printed circuit board. Leads were taken out by soldering them to the PCB breadboard. Two hard electrodes of copper and zinc were placed on either side of the electrolyte (Figure 21, panel C) and output voltage across the two electrodes was measured. The open circuit voltage was found to be approximately 0.9 Volts and the short circuit current is micro ampere. The graph in panel A, Figure 22 shows the load characteristics of the unit cell. Panels B and C of Figure 22 show the load characteristics of two unit cells connected in series and in parallel respectively.

[00107] Next hard electrodes were replaced with thin films of copper and zinc. For this, thin film of zinc and copper were deposited on the surface of the solid electrolyte using DC magnetron sputtering system (Figure 4). The deposition was carried out for about 15-30 minutes

Example 2: Preparation of an edible battery containing a gel electrolyte

[00108] A few gelatin capsules were taken into a glass beaker and heated up to 150°C until the gelatin capsules melted and converted into a liquid form. Liquid gelatin was poured into a small circular plastic cap. After 5 min 3 gelatin capsules were inserted into the cap to make 3 small wells inside the gelatin mould (Figure 23, panel A). After exposing to atmospheric conditions for about 12 hours, the gelatin capsules inserted inside the cap were removed. Three circular wells were formed inside the gelatin, each well having a diameter of about 2mm (Figure 23, panel B). These circular wells can be used to fill the electrolyte which is in gel form and also the electrodes can be dipped inside the well. Three circular wells can form three different batteries.

[00109] The gel form of electrolyte (e.g., electrolyte in pectin or gelatin) was poured into the wells of the mould. Hard copper and zinc electrodes were dipped inside the electrolyte and the output voltage was tested using a multi meter and was found to be 0.9Volts (Figure 23, panel C).

Example 3: Preparation of an edible battery containing a gel electrolyte

[00110] A gelatin capsule was taken as the body of the battery (Figure 5, panel A). To protect the inner layers of the gelatin capsule from the moisture of the electrolyte, sugarin was coated on the inside walls of the gelatin capsule. To do this, the lower part of the gelatin capsule was filled with the sugarin and left in for about 2 min. After two min, the sugarin was poured out. A thin coating of sugarin was observed on the walls of the gelatin capsule (Figure 5, panel B).

[00111] Isomalt was heated up to 200°C to obtain liquid isomalt. This liquid isomalt was cooled for about 30 sec at room conditions. About 2 ml of liquid isomalt was filled into the sugarin-coated gelatin capsule so that it covers a height of about 0.6cm from the bottom of the capsule (Figure 6, panel A). Two thin copper (weight less than lOmg) and zinc (weight less than 40mg) electrodes were dipped into the liquid isomalt. Two thin silver wires (weight less than lOmg) were connected to copper and zinc electrodes (Figure 6, panel B). Silver wires acts as leads of the battery. After inserting the electrodes, the capsule was left for about 5 minutes. After 5 minutes, the liquid isomalt inside the capsule was solidified and acts as the base of the battery. The copper and zinc electrodes used in the design were below the toxicity limits of the human body. A freshly prepared lemon extract (about 2 ml) was filled into the capsule making sure the two electrodes were immersed inside the electrolyte. This covered another 0.6cm height of the capsule . The gelatin capsule was closed using the upper part of the gelatin capsule or the remaining part of the capsule was filled with the isomalt covering the remaining 0.6cm height of the capsule and the capsule was left for some time for the isomalt to solidify (Figure 6, panel C). The electrolyte was sandwiched between the two isomalt layers. This battery gave an output of about 0.9v (Figure 6, panel D). Example 4: Preparation of an edible oscillator

[00112] To prepare an edible oscillator, first an isomalt substrate was prepared. Figure 24A shows a schematic of fabricating an isomalt substrate. Isomalt pellets were heated to form an isomalt solution. The isomalt solution is drop casted on a surface such as polydimethylsiloxane (PDMS). A load was applied through a smooth plate like a glass plate to press the PDMS to form the isomalt substrate. A thin isomalt wafer which can serve as a substrate for various components of the edible electronic device is shown in Figure 24B. Fourier Transform Infrared (FTIR) spectroscopy of the isomalt substrate is shown in Figure 24C. The FTIR spectroscopy indicates presence of C-0 bonds, C-C bonds, C=0 bonds, C-H bonds, and O-H bonds.

[00113] Figure 24D shows the solubility of isomalt substrate and metallized isomalt substrate in water (a thin film of silver was deposited on the isomalt substrate using a vapor deposition method to obtain the metallized isomalt substrate). When metallized isomalt substrate was placed in water, the isomalt dissolved away in approximately about 10 min leaving behind the metal film.

[00114] The isomalt substrate is susceptible to moisture and dissolves rapidly in water. To make isomalt substrate less susceptible to ambient moisture and to extend the dissolution time of isomalt substrate, the fabricated isomalt substrate can be dip-coated with an edible glaze (for example, sugarin) as shown in Figure 24E. Isomalt-sugarin substrate was found to be more resistant to water and did not lose structural integrity for up to 5 hours. In the presence of hydrochloric acid of pH 2, the isomalt-sugarin substrate dissolved in less than 30 min. Since sugarin has a relatively slow dissolving rate, the thickness of the sugarin coating can be controlled to time the exposure of the components inside the patient’s body.

[00115] Panel (a) of Figure 25 shows flexural strength measurements of the isomalt substrate (2 cm diameter and 1mm thickness) at room temperature. The Young’s modulus was found to be around 0.9 + 0.2 GPa. The isomalt substrate transforms from solid to viscoelastic to liquid with an increase in temperature as shown in panel (b) of Figure 25. It was observed that isomalt behaved mostly like a solid at < 50°C. Upon mild heating to just above about 50°C, the isomalt substrate softened and became pliable and the isomalt substrate could be mechanically deformed by manually applied forces. Furthermore, this deformation could be retained (mechanical memory) by cooling the substrate once again. The isomalt substrate are viscoelastic in the temperature range of 50°C to 130°C. Beyond 130°C and up to 200°C, the isomalt substrate behaves like a fluid. The viscosity of the isomalt substrate can be studied using a falling ball viscometer. The viscosity can vary from about 50 Ns/m² at 100°C to 25 Ns/m² at 150°C. The boiling point of the isomalt substrate is observed to be about 220°C. Panel (c) of Figure 25 shows the UV-visible spectroscopy on the isomalt substrate. The UV-visible spectroscopy showed 70% transmittance for a 500 pm thick sample at a wavelength of 550 nm. The wavelengths < 300 nm are absorbed as shown in panel (d) of Figure 25. Panel (e) of Figure 25 shows time resolved fluorescence spectroscopy. The time resolved fluorescence spectroscopy shows fluorescence at an excitation wavelength of 270 nm.

[00116] Silver interconnects in the shape of a coil were deposited on the isomalt substrate as shown in Figure 8, panel A. The silver coil on the isomalt substrate acts as an inductor coil. Figure 8, panel B shows impedance spectrum Z_L (to) of the inductor coil fabricated with w=2pί. The w refers to angular frequency and f refers to frequency in Hz. Figure 8, panel B shows magnitude |Z_L (co)|, as a function of f. It can be inferred that significant parasitic resistance dominated the impedance at low frequencies with inductive component beginning to dominate at frequencies greater than 5 MHz. Figure 8, panel C shows phase arg[Z_L (to)] as a function of frequency. The phase begins to head towards +90° at high frequencies. In some embodiments, the edible substrate (e.g., isomalt) is coated with a slow-release coating (e.g., sugarin) and then an edible conductor (e.g., silver) is deposited onto the coated substrate.

[00117] To prepare a three-dimensional coil inductor, the isomalt was melted to form the isomalt solution. The isomalt solution was spooled (Figure 9, panel A) and sculpted to form a three-dimensional inductor (Figure 9, panel B). Silver was deposited onto the three- dimensional isomalt coil using vapor deposition (Figure 9, panel C). Figure 9, panel D shows impedance spectrum Z_L (to) of the three-dimensional inductor fabricated (7 turns, 1.6 cm long, 4 mm inner radius). Figure 9, panel D shows magnitude |Z_L (co)| as a function of f. Once again, the significant parasitic resistance dominates the low frequency impedance with the inductive component becoming prominent at f> 5MHz. Figure 9, panel E shows the phase arg[Z_L (to)] as a function of frequency. The phase begins to head towards +90° at high frequencies.

[00118] In another experiment, isomalt was melted to form the isomalt solution; 5 pg of iron particles were added to 100 mg of melted isomalt; and the mixture was poured into a mould to form an edible ferrite core (Figure 10, panel A). As can be seen from Figure 10, panel B, the ferrite core formed has magnetic properties, that is the ferrite core is attracted towards a magnet. A coil of silver was deposited on the ferrite core (Figure 10, panel C) which further enhances the inductance. This silver-coated ferrite isomalt core as the inductor. After the layer of silver was deposited, contacts were provided to the three-dimensional inductor. Panel D of Figure 10 shows impedance spectrum Z_L (to) of the three-dimensional inductor fabricated with the ferrite core. A wider track width helped reduce the parasitic resistance but increased the length of the inductor resulting in an inductance of approximately 100 nHto 200 nH. Panel E of Figure 10 shows phase of the three-dimensional inductor with the ferrite core as a function of frequency. Figure 11 shows inductances and resistances of the two-dimensional silver inductor coil, the three-dimensional silver-coated isomalt-coil inductor, and the three-dimensional silver coil with the ferrite core inductor.

[00119] A capacitor was fabricated by depositing silver (Ag) on the top and bottom sides of the isomalt substrate (Figure 13, panel D) by thermal vapor deposition or a physical vapor deposition process through the shadow mask.

Example 5: Preparation of an edible diode, resistor, and transistor

[00120] To prepare an edible diode shown in Figure 17, panels G and H, a sugar paper of required dimensions was baked on a hotplate at 140°C for 90 minutes. Gold was deposited by sputtering and aluminium was deposited by thermal evaporation. Zinc oxide was deposited using reactive DC sputtering with Zn and target at appropriate oxygen partial pressure.

[00121] A similar process can be used to prepare resistors and transistors.

Claims

1. An edible electronic device comprising at least one of each of the following component: a. a battery; b. a sensor; c. a signal modulation unit connected to the battery and the sensor; and d. a communication unit connected to the battery and the signal modulation unit.

2. The edible electronic device as claimed in claim 1, wherein the battery is configured to provide power to the components of the edible electronic device; the sensor is configured to sense one or more clinical parameters and provide an output to the signal modulation unit; the signal modulation unit is configured to receive the sensor output, convert it into an output signal having various frequency components, and provide the output signal to the communication unit; and the communication unit is configured to transmit the output signal having various frequency components to an external transceiver unit.

3. The edible electronic device as claimed in claim 1 or 2, wherein the battery, the signal modulation unit, and the communication unit are located inside a housing and the sensor is located outside and/or inside the housing.

4. The edible electronic device as claimed in claim 3, wherein the housing comprises gelatin, cellulose, starch, sugarin, other standard clinical grade materials or a combination thereof.

5. The edible electronic device as claimed in any one of claims 2-4, wherein the housing is surrounded by a slow release coating.

6. The edible electronic device as claimed in claim 5, wherein the slow-release coating comprises sugarin.

7. The edible electronic device as claimed in any one of claims 1-6, wherein the battery comprises a carrier comprising an electrolyte, a cathode, an anode, a terminal connected to the cathode and a terminal connected to the anode.

8. The edible electronic device as claimed in claim 7, wherein the carrier is solid or gel.

9. The edible electronic device as claimed in claim 7 or 8, wherein the carrier is pectin, gelatin, isomalt, sugarin, sugar paper, or a combination thereof.

10. The edible electronic device as claimed in any one of claims 7-9, wherein the carrier is a gelatin capsule comprising a sugarin coating.

11. The edible electronic device as claimed in any one of claims 7-9, wherein the carrier is a gelatin capsule comprising a sugarin coating and isomalt.

12. The edible electronic device as claimed in any one of claims 6-11, wherein the electrolyte is selected from the group consisting of lemon extract, orange extract, a potato extract, gastric juice, citric acid, malic acid, tartaric acid, oxalic acid, fumaric acid, succinic acid and a combination thereof.

13. The edible electronic device as claimed in any one of claims 6-12, wherein the electrolyte is embedded in pectin as the carrier.

14. The edible electronic device as claimed in any one of claims 6-12, wherein the electrolyte is in a well of isomalt in a sugarin-coated gelatin capsule.

15. The edible electronic device as claimed in any one of claims 6-12, wherein the electrolyte is sandwiched between layers of isomalt in a sugarin-coated gelatin capsule.

16. The edible electronic device as claimed in any one of claims 6-15, wherein the cathode is selected from the group consisting of copper, silver, and iron.

17. The edible electronic device as claimed in any one of claims 6-16, wherein the cathode is in the form of a fdm or a wire.

18. The edible electronic device as claimed in any one of claims 6-17, wherein the anode is selected from the group consisting of zinc, magnesium, aluminium, and sodium.

19. The edible electronic device as claimed in any one of claims 6-18, wherein the anode is in the form of a fdm or a wire.

20. The edible electronic device as claimed in any one of claims 6-19, wherein the terminal connected to the cathode and the terminal connected to the anode comprise silver or other edible conductors.

21. The edible electronic device as claimed in any one of claims 1-20, wherein the sensor detects a parameter selected from pH, internal bleeding, acidity, pathogen causing an infection or a combination thereof.

22. The edible electronic device as claimed in any one of claims 1-21, wherein the sensor comprises a sensing component in contact with a first and a second metal, a conductor connected to the first metal and a conductor connected to the second metal.

23. The edible electronic device as claimed in claim 22, wherein the sensing component is selected from the group (but not limited tojconsisting of lemon extract, orange extract, a potato extract, gastric juice, citric acid, malic acid, tartaric acid, oxalic acid, fumaric acid, succinic acid a combination thereof.

24. The edible electronic device as claimed in claim 22 or 23, wherein the first and the second metal are selected from copper, silver, iron, zinc, magnesium, aluminium, and sodium.

25. The edible electronic device as claimed in any one of claims 22-24, wherein the conductor connected to the first metal and the conductor connected to the second metal comprise silver or other edible conductors.

26. The edible electronic device as claimed in any one of claims 1-25, wherein the signal modulation unit comprises a signal source connected to a linear device, the linear device connected to a non-linear device and the non-linear device connected to the sensor.

27. The edible electronic device as claimed in claim 26, wherein the signal source is selected from (i) an oscillator comprising an inductor and a capacitor; (ii) an oscillator comprising an inductor, a capacitor, and a transistor; (iii) an antenna receiving a signal from outside; or (iv) a MEMS resonator.

28. The edible electronic device as claimed in claim 27, wherein the inductor comprises an edible conductor deposited on an edible substrate.

29. The edible electronic device as claimed in claim 28, wherein the edible substrate is isomalt and the edible conductor is silver.

30. The edible electronic device as claimed in claim 28, wherein the inductor comprises a two-dimensional silver coil on an isomalt substrate.

31. The edible electronic device as claimed in claim 28, wherein the inductor comprises a three-dimensional isomalt coil coated with a silver layer or silver particles.

32. The edible electronic device as claimed in claim 28, wherein the inductor comprises an isomalt substrate embedded with iron nanoparticles and coated with a silver coil.

33. The edible electronic device as claimed in claim 27, wherein the capacitor comprises a first edible conductor in contact with an edible insulator in contact with a second edible conductor.

34. The edible electronic device as claimed in claim 33, wherein the edible insulator is coated with a slow release coating.

35. The edible electronic device as claimed in claim 34, wherein the slow release coating is a sugarin coating.

36. The edible electronic device as claimed in claim 33, wherein the first and the second edible conductor is selected from aluminium, silver, or copper and the edible insulator is selected from isomalt, sugarin, albumin, cellulose, or a combination thereof.

37. The edible electronic device as claimed in claim 33, wherein the capacitor comprises a first layer of silver, a second layer comprising a sugarin-coated isomalt, and a third layer of silver.

38. The edible electronic device as claimed in claim 27, wherein the transistor comprises a metal connected to an insulator connected to an edible semiconductor connected a first and a second ohmic contact.

39. The edible electronic device as claimed in claim 38, wherein the metal is selected from aluminium, silver, or gold; the insulator is selected from isomalt, sugarin, an oxide, xanthan gum, sugar paper, cotton, egg albumen, gelatin, jute, or a combination thereof; the edible semiconductor is selected from zinc oxide or amorphous silicon; and the first and the second ohmic contact comprises aluminium, magnesium, calcium or other low workfimction metals for electron transporting semiconductors or gold, silver, or other high workfimction metals for hole transporting semiconductors.

40. The edible electronic device as claimed in claim 39, wherein the transistor comprises an edible substrate as a support.

41. The edible electronic device as claimed in claim 40, wherein the edible substrate is selected from a sugar paper, isomalt, sugarin, an oxide, cotton, egg albumen, gelatin, jute, or a combination thereof.

42. The edible electronic device as claimed in claim 27, wherein the antenna comprises an edible conductor coated on an edible substrate.

43. The edible electronic device as claimed in claim 42, wherein the edible conductor is silver and the edible substrate is isomalt or isomalt comprising a sugarin coating.

44. The edible electronic device as claimed in claim 26, wherein the linear device is a resistor comprising an edible semiconductor connected to a first and a second edible ohmic contact.

45. The edible electronic device as claimed in claim 44, wherein the edible semiconductor is selected from zinc oxide or amorphous silicon; and the first and the second ohmic contact comprises aluminium, magnesium, calcium or other low workfimction metals for electron transporting semiconductors or gold, silver, or other high workfimction metals for hole transporting semiconductors.

46. The edible electronic device as claimed in claim 44 or 45, the resistor comprises an edible insulator substrate to support the semiconductor and the ohmic contacts.

47. The edible electronic device as claimed in claim 46, wherein the edible insulator substrate is selected from a sugar paper, isomalt, sugarin, an oxide, xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof.

48. The edible electronic device as claimed in claim 26, wherein the non-linear device is a diode or a transistor.

49. The edible electronic device as claimed in claim 48, wherein the diode comprises an edible semiconductor connected to a Schottky contact and an ohmic contact.

50. The edible electronic device as claimed in claim 49, wherein the edible semiconductor is selected from zinc oxide or amorphous silicon; the Schottky contact comprises gold, silver or other high workfunction materials for electron transporting semiconductors or aluminium, calcium, magnesium, or other low workfunction materials for hole transporting semiconductors; and the ohmic contact comprises aluminium, magnesium, calcium or other low workfunction metals for electron transporting semiconductors or gold, silver, or other high workfunction metals for hole transporting semiconductors.

51. The edible electronic device as claimed in claim 49 or 50, wherein the diode comprises an edible insulator substrate to support the semiconductor, the Schottky contact and the ohmic contact.

52. The edible electronic device as claimed in claim 51, wherein the edible insulator substrate is selected from a sugar paper, isomalt, sugarin, an oxide, xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof.

53. The edible electronic device as claimed in claim 48, wherein the transistor comprises a metal connected to an insulator connected to an edible semiconductor connected a first and a second ohmic contact.

54. The edible electronic device as claimed in claim 53, wherein the metal comprises aluminium, silver, or gold; the insulator is selected from a sugar paper, isomalt, sugarin, an oxide, xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof; the edible semiconductor comprises zinc oxide or amorphous silicon; and the first and the second ohmic contact comprises aluminium, magnesium, calcium or other low workfunction metals for electron transporting semiconductors or gold, silver, or other high workfunction metals for hole transporting semiconductors.

55. The edible electronic device as claimed in claim 53 or 54, wherein the transistor comprises an edible insulator substrate as a support.

56. The edible electronic device as claimed in claim 55, wherein the edible insulator substrate is selected from a sugar paper, isomalt, sugarin, an oxide, xanthan gum, cotton, egg albumen, gelatin, jute, or a combination thereof.

57. The edible electronic device as claimed in any one of claims 1-56, wherein the communication unit comprises (i) a signal source or (ii) a signal source and an amplifier.

58. The edible electronic device as claimed in claim 57, wherein the signal source is a transmitter antenna or a MEMS resonator.

59. The edible electronic device as claimed in claim 58, wherein the transmitter antenna comprises an edible conductor coated on an edible substrate.

60. The edible electronic device as claimed in claim 59, wherein the edible conductor is silver and the edible substrate is isomalt or isomalt comprising a sugarin coating.

61. The edible electronic device as claimed in claim 57, wherein the amplifier comprises one or more components selected from a transistor, an inductor, a resistor, and a capacitor.

62. A system comprising the edible electronic device as claimed in any one of claims 1-61 and an external transceiver unit configured to receive the output signal having various frequency components from the edible electronic device and optionally to transmit a signal to the signal modulation unit of the edible electronic device.

63. The system as claimed in claim 62, wherein the transceiver unit comprises one or more components selected from a memory, battery, sensors and actuators, transceivers, MEMS resonators and a computation unit.