WO2002007598A1

WO2002007598A1 - Ingestible electronic capsule

Info

Publication number: WO2002007598A1
Application number: PCT/US2001/023374
Authority: WO
Inventors: Vijay Nair; Piotr Grodzinski; Nada A. El-Zein; Herbert Goronkin
Original assignee: Motorola, Inc.
Priority date: 2000-07-24
Filing date: 2001-07-24
Publication date: 2002-01-31
Also published as: JP2004516863A; AU2001277163A1; EP1304959A1; US20020132226A1

Abstract

An improved and novel ingestible capsule (10) and method for determining medical information from within the alimentary canal of a human or an animal utilizing the ingestible capsule including a non-digestible outer shell (20) that is configured to pass through the alimentary canal. A marker membrane (12) is exposed through a portion of the non-digestible outer shell. The marker membrane is characterized as detecting and identifying predetermined detectable information. Housed within the non-digestible outer shell are a bio-sensor (14) that alters its electronic properties in the presence of specific information obtained by the marker membrane from within the alimentary canal, a low frequency transducer (16) that sends a signal of the changed electronic properties to a receiver positioned outside the body and a miniature battery (18) for powering the transducer.

Description

INGESTIBLE ELECTRONIC CAPSULE

Field of the Invention

The present invention relates to a novel ingestible capsule for use in the field of medicine and method of using the capsule for the accumulation of medical data within the body of animals, and in particular humans.

Background of the Invention

It is highly desirable to obtain certain medical information and detect certain medical diseases, in particular cancer, without the painful invasive procedures currently used in the medical field. Many of these procedures are unduly stressful and in extreme cases, deter the patient from seeking medical assistance and initial diagnosis. Invasive procedures, or those medical procedures which require the entering of a part of the body, as by incision, scope, etc., are commonly utilized to diagnosis certain diseases and includes procedures such as those utilizing needles, flexible tubes, endoscopic procedures, and surgical procedures.

Many of these diagnostic procedures rely upon the specific procedure or device utilized and the skill of the operator of the device or the one performing the procedure. One such procedure that is typically used today as a common diagnostic tool is colonoscopy for the detection of colorectal cancer (CRC). A colonoscopy generally includes direct visual examination of the colon, ileocecal value, and portions of the terminal ileum by means of a fiberoptic endoscope. A colonoscopy is typically performed by a qualified gastroenterologist. During a colonoscopy the patient is generally awake but sedated. During the procedure a flexible endoscope is inserted in rectum and advanced through the various portions of the lower GI tract. Important anatomic landmarks are identified and surfaces are examined for ulcerations, polyps, hemorrhagic sites, neoplasms, strictures, etc. Dependent upon identified conditions, colorectal cancer, or precancerous conditions of the colon are diagnosed. In many instances, of this invasive procedure, complications arise. The most common complication being perforation of the colon in which diagnosis may be delayed for days until an infection is present. Perforation may be caused by mechanical trauma from the instrument tip, especially if the wall is weakened. Less commonly, perforation may be non-instrumental, secondary to aggressive insufflation with air. However, serious complications from perforation have been reported in routine cases. In addition, hemorrhaging can arise as a complication and many times requires repeat colonoscopy to coagulate the bleeding. In a few instances angiography and surgery have been required. A third less common complication is respiratory depression, which is usually due to oversedation in the patient with chronic lung disease. Other common diagnostic procedures include digital rectal exams, fecal occult blood tests (FOBT) utilizing stool samples, barium enema x-rays, and endoscopic sigmoidoscopy. These procedures are all utilized to diagnose cancerous conditions. During an endoscopic sigmoidoscopy, direct examination of the rectum, sigmoid colon, and proximal portions of the colon (60 cm) is achieved by means of a flexible fiberoptic endoscope. The procedure is generally performed in a physician's office with minimal bowel preparation. The 35 cm scope is more comfortable and less expensive than its larger counterpart, the colonoscopy. Although, the yield of this instrument is somewhat less, with only 40% of malignant or premalignant colonic lesions diagnosed.

All of these procedures are termed invasive procedures and can cause high level of discomfort for the patient. Therefore it is desirable to have a non-invasive procedure that can detect diseases, and/or conditions, such as cancer or the like in their very early stages.

In addition, the medical community has recognized a need for more reliable and less invasive procedures for the detection and thus diagnosis of medical diseases. In recent years "radio pills" have come into being. These pills provide for a means to monitor bodily factors and can either be implanted or ingested and provide for the transmission of information outside of the body. Many of these devices have been quite cumbersome in receiving means, as well as unreliable and generally do not provide for determination of the geographic location of the pill.

Many cancer detection means are known in the medical field, one of such is the use of cancer markers. In order to develop a successful screening procedure for detection of various diseases, including cancer, identification of appropriate and reliable diagnostic markers is essential. There are typically three (3) general categories of such markers: physical, genetic and chemical. One such procedure currently being utilized in the medical field to detect early stages of pre-colon cancer polyp development, is the physical characterization of inner surfaces of the intestine using the endoscopy imaging techniques, such as those previously described with respect to colonoscopy, and flexible sigmoidoscopy. It should be noted that both physical and genetic markers would be difficult to assess using in-vivo detection schemes. Physical markers need to deal with position control, GI tract content interference with the observation, and large amounts of data transmittal. Genetic markers would be difficult to pursue due to the complexity of DNA analysis and detection in a very small volume of the detector. Therefore, chemical detection means are the most logical to pursue for in-vivo mode of detection. Accordingly, it is an object of the present invention to provide for a device for the detecting and diagnosing of medical conditions utilizing chemical markers.

It is another object of the present invention to provide for a device that is ingestible, such as a capsule, that can transmit diagnostic information to a remote receiver, positioned external to the body, that is reactive upon the sensing of a predetermined factor according to the diagnostic marker utilized.

It is yet another purpose of the present invention to provide for a process of receiving information and diagnosing medical conditions by introducing an ingestible capsule into the body, which is capable of transmitting perceived information based upon detection of a predetermined condition utilizing a chemical marker.

Summary of the Invention These needs and others are substantially met through provision of an ingestible capsule for determining medical information from within the alimentary canal of a human or an animal including a non-digestible outer shell that is configured to pass through the alimentary canal. A marker membrane is exposed through a portion of the non-digestible outer shell. The marker membrane is characterized as detecting and identifying predetermined detectable information. The marker membrane includes a portion exposed to the surrounding environment through which the capsule passes. Housed within the outer shell are a bio-sensor that alters its electronic properties in the presence of specific information obtained by the marker membrane from within the alimentary canal, a low frequency transducer that sends a signal of the changed electronic properties outside the body and a miniature battery for powering the transducer.

In addition, disclosed is a method for obtaining diagnostic medical information by ingesting a capsule including a marker membrane, or receptor, characterized as identifying predetermined detectable information, a bio-sensor that alters its electronic properties in the presence of specific information obtained by the marker membrane, a low frequency transducer that sends a signal of the changed electronic properties to outside the body, and a miniature battery for powering the transducer. The bio-sensor is responsive to an electrical signal that is produced when the marker membrane, or receptor, interacts with the substance of interest in the tested sample. This change in electrical signal is recognized by the transducer, which submits a signal to a receiver positioned external the body. Brief Description of the Drawings

FIG. 1 illustrates a cross-sectional view of an ingestible capsule according to the present invention; and

FIG. 2 illustrates a simplified schematic circuit diagram of the ingestible capsule according to the present invention.

Detailed Description of the Preferred Embodiments

During the course of this description, like numbers are used to identify like elements according to the different figures that illustrate the invention. Accordingly, FIG. 1 illustrates in simplified cross-sectional view an ingestible capsule according to the present invention. More specifically, illustrated in FIG.l, is an ingestible capsule, designated 10 and the manner in which the components housed with ingestible capsule 10 are interrelated in general. Ingestible capsule 10 typically comprises a chemical marker membrane 12, an electronic bio-sensor 14, a transducer 16 and a power source 18, such as a miniature battery power source. Components 12, 14, 16 and 18 are interrelated to provide for the detection of a predetermined factor or condition, such as the presence of an enzyme, antigen, antibody, specific pH level, or the like.

During typical operation, ingestible capsule 10 is swallowed by a "patient" similar to a conventional pill/capsule and propelled through the alimentary canal by natural contractions, called peristalsis. Marker membrane 12 is fabricated to detect the presence of a specific condition, such as a level of enzyme, antigen, antibody, pH, etc.. Bio-sensor 14 is interrelated with the marker membrane 12 and is characterized as altering its electronic properties in the presence of specific information obtained by the marker membrane 12 and submits an electrical signal which turns on power source 18. Low frequency transducer 16 is then switched on by the change in electrical properties and the power source and is characterized as sending a signal of the changed electronic properties to outside the body. This signal of changed electronic properties, meaning the presence of a predetermined factor or condition, is transmitted by the transducer, in the form of a radio frequency signal, to a receiver 22 that is positioned external the body.

Capsule 10 is fabricated small enough to be easily swallowed by a human or animal. Typically capsule 10 is fabricated less than 11x30mm, or approximately less

than 1" long, by less than " wide and is fabricated of a sealed, non-digestible outer

shell 20, having exposed marker membrane 12, that is shaped so as to easily pass through the alimentary canal. While it is stated that marker membrane 12 is exposed to the surrounding environment within the alimentary canal, it should be understood that anticipated by this disclosure is the initial covering of marker membrane 12 with a dissolvable material. More particularly, it is anticipated that marker membrane 12 can be initially covered by a dissolvable membrane (not shown), characterized as dissolving to expose marker membrane 12 at a specific time/point relative to the alimentary canal. Capsule 10 does not include any external wires, fibers, optical bundles or cables, although it is anticipated that capsule 10 can additionally include optical components, etc., to further aid in diagnosing. As previously stated, capsule 10 is propelled by peristalsis, or natural contractions, through the gastrointestinal tract and does not require any pushing force to propel it through the bowel.

The premise for operation of capsule 10 is biosensing. Typically biosensing involves a device that contains biological materials, such as enzymes, cells, antibodies, antigens, or the like, immobilized in conjunction with a transducer which is able to produce an electrical signal when the biological material (receptor) interacts with the substance of interest in the tested sample. There are several ways to achieve this sensing which can be utilized in capsule 10 of the present invention. More particularly, in capsule 10 of the present invention, marker membrane 12 is utilized to detect the existence of certain pre-identified condition or material. Marker membrane 12 is disclosed as including a chemical marker, and formed such as ion sensitive field effect transistors (ISFETs) in which marker membrane 12 is formed as a functionalized membrane that is deposited on the gate of the transistor. The membrane is responsive to a specific chemical that is sought to be detected, such as that indicative of a cancer precursor. Once the chemical is detected, it will trigger a certain response from the ISFET that can be detected. In particular, the interaction between the membrane 12 and the chemical causes the electrical behavior of the FET to change. This change of response of the FET, is monitored to determine the presence of the appropriate chemical, such as glucose, ascorbic, citric acids, or pH measurements. Examples of chemical markers which can be utilized are found in the following articles: "Glucose, Ascorbic and Citric Acids Detection by two-ISFET Multienzyme Detector", N. Noltsky, Ν. Kim, Sensors and Actuators, B 49 (1998), 253-257; "H+ ISFET - Based Biosensor for Determination of Penicillin", J. Liu, L. Liang, G. Li, R. Han, K. Chen, Biosensors and Bioelectronics, 13 (1998), 1023-1028; and "pH Measurements with an ISFET in the Mouth of Patients with Xerostomia", L.L. Nisch, P. Bergveld, W. Lamprecht, and E.J. Gravenmade, IEEE Transactions on Biomedical Engineering, Vol. 38, No. 4 (1991), 353-356.

Another type of marker that can be utilized in conjunction with membrane 12 is through the impedimetric measurements on functionalized electrodes. In this case, platinum, gold, or other metal electrodes are coated with molecules that are sensitive to the chemical or biological material that is trying to be sensed. When the reaction happens, the molecule present on the electrode binds to the chemical that is being sensed causing a change in the impedance (i.e. conductivity) through the electrode. This can be sensed through the electronics of bio-sensor 14 and a signal is produced by transducer 16. Examples of this time of marker are further discussed in the following articles: "Impedimetric Measurements on Polarized Functionalized Platinum Electrodes: Application to Direct Immunosensing", S. Ameur, H. Maupas, C. Martelet, N. Jaffrezic-Renault, H. Ben Ouada, S. Cosnier, P. Labbe, Materials Science Engineering, C5, (1997), 111-119; and "Sensitive Electrochemical Detection of Antigens Using Gold Electrodes Functionalized with Antibody Moieties", S. Ameur, C. Martelet, J.M. Chovelon, H. Ben Ouada, N. Jaffrezic-Renault, D. Barbier, Proceedings of the 12^th European Conference on Solid State Transducers and the 9^th UK Conference on Sensors and their Applications (1998) Vol., 2, 797-800. These two types are the most commonly used electrochemical sensing devices utilizing certain biological markers. In addition, traditional methods of biological targeting are anticipated for use in the ingestible capsule of the present invention, such as, where biological targets are tagged with fluorescent or radioactive molecules and are then imaged through MRI, scopes, or any other optical detection method.

Once the chemical marker membrane 12 detects the presence of an identified antigen, antibody, or condition selective to a disease that is sought to be detected, a signal is generated by the bio-sensor 14. This signal is transmitted to transducer 16 which submits a radio frequency signal to external receiver 22, either at an ultrasonic frequency or dependent upon a range of detection and sensitivity of the included receiver, from an audio to microwave frequency range. Transducer 16 is described as being a miniature transducer that is fabricated on a ceramic or plastic material.

Transducer 16 is fabricated to utilize a very low voltage on the order of 1.5-3.0 volts.

During operation, the electrical property such as conductivity or potential across bio-sensor 14 changes. This change of electrical property turns on a switch that in turn provides power from power source 18 to transducer 16. Transducer 16 in turn emits a signal as it travels through a region that has activated chemical marker membrane 12. As the ingestible capsule 10 moves away from the region in which chemical marker membrane 12 is responsive, the switch is turned off. Accordingly, as the degree of responsiveness increases, as the severity increases. It should be understood that it is anticipated by this disclosure that numerous marker membranes 12 can be utilized with differing chemical markers, thereby serving as a diagnostic tool for a plurality of conditions, simultaneously. Additionally, a positioning indicator (not shown) can optionally be included for the purpose of determining the exact position of the capsule 10 at any given time in the alimentary canal.

Referring now to FIG. 2, illustrated is a simplified electronic schematic circuit diagram of the ingestible capsule of the present invention. Illustrated by dashed lines, is a sensing circuit 30, including marker membrane 12 and bio-sensor 14, a driver circuit 32, including power source 18, and a transducer circuit 34, including transducer 16. During operation, in the absence of detection by sensor circuit 30 thus the generation of a signal, there is not enough voltage across transducer 16 to turn it "ON". When biosensor circuit 30 is turned "ON", due to the reaction of marker membrane 12 with the detection of an identified material, the transducer circuit 34 is turned "ON" to produce enough voltage to drive transducer 16 and thus submit a signal to receiver 22.

Thus, an ingestible capsule including a small power source, such as a battery, that is connected to a transducer through a bio-sensor switch is disclosed. When the electrical property such as the conductivity or potential across the bio-sensor changes, it turns on the switch that in turn provides power to the transducer. The transducer then emits the signal to an externally located receiver as it travels through the region in which a predetermined substance of interest has been identified.

Claims

What is claimed is:

1. An ingestible capsule for determining medical information from within the alimentary canal of a human or an animal comprising: a non-digestible outer shell that is configured to pass through the alimentary canal, the non-digestible outer shell housing within; a marker membrane exposed through a portion of the non-digestible outer shell, the marker membrane characterized as identifying predetermined detectable information; a bio-sensor that alters its electronic properties in the presence of specific information obtained by the marker from within the alimentary canal; a low frequency transducer that sends a signal of the changed electronic properties to outside the body; and a power source for powering the transducer.

2. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the marker membrane includes a chemical marker.

3. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the chemical marker reacts to a pre-identified condition, characterized as a level of enzyme, antigen, or antibody.

4. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 3 wherein the bio-sensor submits an electrical signal in response to the chemical marker which turns on the power source.

5. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the power source is a miniature battery.

6. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the transducer is a miniature transducer formed on a ceramic or a plastic material.

7. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the transducer emits a radio frequency signal to an externally remote receiver.

8. An ingestible capsule for determining medical information in the body of a human or an animal as claimed in claim 1 wherein the transducer emits an audible signal to an externally remote receiver.

9. An ingestible capsule for determining medical information from within the alimentary canal of a human or an animal comprising: a non-digestible outer shell that is configured to pass through the alimentary canal, the non-digestible outer shell housing within; a marker membrane including a chemical marker and being exposed through a portion of the non-digestible outer shell, the marker membrane characterized as identifying predetermined detectable information; a bio-sensor that alters its electronic properties in the presence of specific information obtained by the chemical marker membrane from within the alimentary canal; a low frequency transducer that sends a signal of the changed electronic properties to a remote receiver positioned outside the body; and a miniature battery for powering the transducer.

10. A method for obtaining diagnostic medical information comprising the steps of: ingesting a capsule including a marker membrane including a chemical marker, the marker membrane characterized as identifying predetermined detectable information, the capsule further including a bio-sensor that alters its electronic properties in the presence of specific information obtained by the chemical marker membrane, a low frequency fransducer that sends a signal of the changed electronic properties to outside the body, and a miniature battery for powering the transducer; and remotely positioning a receiver characterized as receiving the signal from the transducer.