WO2005115225A2 - Intraoral apparatus and method for blood and saliva monitoring & sensing - Google Patents
Intraoral apparatus and method for blood and saliva monitoring & sensing Download PDFInfo
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- WO2005115225A2 WO2005115225A2 PCT/IL2005/000542 IL2005000542W WO2005115225A2 WO 2005115225 A2 WO2005115225 A2 WO 2005115225A2 IL 2005000542 W IL2005000542 W IL 2005000542W WO 2005115225 A2 WO2005115225 A2 WO 2005115225A2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
- A61B5/6813—Specially adapted to be attached to a specific body part
- A61B5/6814—Head
- A61B5/682—Mouth, e.g., oral cavity; tongue; Lips; Teeth
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C13/00—Dental prostheses; Making same
- A61C13/225—Fastening prostheses in the mouth
- A61C13/26—Dentures without palates; Partial dentures, e.g. bridges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C13/00—Dental prostheses; Making same
- A61C13/225—Fastening prostheses in the mouth
- A61C13/267—Clasp fastening
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
- A61C8/0048—Connecting the upper structure to the implant, e.g. bridging bars
Definitions
- the present invention relates to body fluids sensing and monitoring, and more particularly, to oral devices and methods that provide sampling method and monitoring of blood, saliva, other oral fluids, such as sputum and crevicular fluid, and various internal body fluids, and manners of clinical sampling and analyzing.
- the present invention relates generally to blood and oral fluids diagnostics and specifically to a method and a test kit for non-invasive (or minimally invasive), blood and oral fluids sampling in a human subject utilizing the collection of blood and oral fluids from the oral tissues and cavity of the patient.
- Blood and oral fluids are obtained from the tissues using mainly reverse drug delivery techniques such as iontophoresis, sonophoresis, RF microchanneling techniques.
- the sample is taken out to an external sampling analyzer and/or analyzed by built-in sensors and the results are transmitted to an extraoral monitoring device or to a controlled drug delivery system or other therapeutic system, such as an electrostimulator to deliver the appropriate dosage or stimulation based on the sensing results.
- Electrotransport refers to at least one, and possibly a combination of transport mechanisms, which supplement the naturally occurring transfer modes.
- Electroosmosis involves the movement of a solvent with the agent through a membrane under the influence of an electric field. Electrophoresis is based on migration of charged species in an electromagnetic field. Ions, molecules, and particles with charge carry current in solutions when an electromagnetic field is imposed. Movement of a charged species tends to be toward the electrode of opposite charge. The voltages for continuous electrophoresis are rather high
- Electroporation is the process in which a biological barrier is subjected to a high voltage alternating-current (AC) surge, or pulse.
- the AC pulse creates temporary pores in the biological membrane, specifically between cells. The pores allow large molecules, such as proteins, DNA, RNA, and plasmids to pass through the biological barrier.
- Iontophoresis is a method of transdermal local drug delivery using electrical current. A charged, ionic drug is placed on the skin with an electrode of the same charge, allowing direct current to drive the drug into the skin
- Reverse iontophoresis is a process that uses electric current to draw biologically important species (such as glucose) from the sub-tissue space to the skin/tissue surface.
- Sonophoresis is a transport method based on the use of ultrasonic means. By applying ultrasound vibrations (a low frequency of between 20 kHz and less than 1.5
- Radio-frequency-driven micro-channeling increasing the skin penetration for selected drugs using a microelectronic device based on ablation of outer layers of tissues (skin, mucosa) using radiofrequency high-voltage currents. These radiofrequency currents created an array of microchannels (across the stratum corneum deep into the epidermis in the skin).
- Membrane-coated collecting container consists of core coated by a substantially insoluble polymer, for example, polyvinyl chloride, wherein the coating is mixed with a water soluble, pore-forming compound.
- Micro-needles a process for the fabrication of out-of-plane hollow microneedles in silicon.
- the fabrication method consists of a sequence of deep-reactive ion etching (DRIE), anisotropic wet etching and conformal thin film deposition, and allows needle shapes with different, lithography-defined tip curvature.
- Reverse micro-needles array for extracting blood samples through the tissues. Vacuum may be applied inside the capsule in synchronization to the activation of other permeability enhancer such as iontophoresis and/or sonophoresis, attracting the egress fluids into the reservoir.
- Sampling and blood monitoring in Veterinary Medicine The use of blood and oral fluid sampling in veterinary medicine presents several challenges: i. there is a multitude of animals of different size and character, and there are anatomical, physiological and behavioral constrains particular to different animals; ii.
- FIG. 1 is a cross-sectional view of a tooth 10, as taught, for example, by www.dentalreview.com/tooth anatomv.htm. As seen in the figure, the basic parts of a tooth are: a crown 12, the portion of tooth above a gum 14, and a root or roots 16, which anchor the tooth in a jawbone 15.
- a pulp 18 is arranged within a pulp chamber 20 and within a root canal or root canals 22.
- Crown 12 is formed of an inner structure of dentine 26 and an external layer of enamel 24, which defines a chewing surface 28.
- Each has an external layer of cement 30, inner structure of dentine 26, and one root canal 22.
- Pulp 18 is formed of tiny blood vessels, which carry nutrients to the tooth, and nerves, which give feeling to the tooth. These enter root canals 22 via accessory canals 32 and root-end openings 34.
- Tooth 10 may define a cylindrical coordinate system of a longitudinal axis x, and a radius r.
- a coronal or incisal end 36 may be defined as the end above gum 14 and a apical end 38 may be defined as the end below it.
- Various intraoral devices and dental reconstruction and repair methods that relate to the present invention are reviewed in conjunction with Figures 2A - 7C, hereinbelow.
- Bridge A bridge may be used to fill a gap of up to four teeth, where there are healthy natural teeth on either side of the gap.
- Figures 3 A - 3F illustrate an application of a three-unit bridge 60 between two healthy teeth 62 and 64. As seen in Figures 3A - 3B, the dentist will prepare teeth 62 and 64 on either side of the gap by removing portions of the enamel and dentin, leaving stumps 66 and 68.
- FIG. 3C - 3D illustrates impressionions or molds of stumps 66 and 68 and the gap between them. In the meantime, a temporary bridge is applied to protect the exposed stumps and provisionally restore the missing teeth.
- the dentist then fits bridge 60, which includes a prosthetic tooth crown 70, over stumps 66 and 68. If the fit is good, he cements bridge 60 into place, restoring function to the area.
- Figures 3E - 3F illustrate an alternative technique: a bridge 72 may be formed of prosthetic tooth crowns 70 and anchors 74, adapted to clamp onto healthy teeth 62 and 64. Unlike bridge 60 of Figures 3C - 3D, which is cemented into place, bridge 72 may be removed, for example, for cleaning.
- dental-implant-and-prosthetic- tooth-crown 80 may be used as an alternative to a bridge.
- dental-implant-and-prosthetic- tooth-crown 80 includes, for example, a dental implant or fixture 82, surgically implanted into the bone, which grows around it. Once dental implant 82 is anchored in the bone, a stump 84 is mounted on it and prepared to accept prosthetic tooth crown 70.
- Dentures When several teeth are missing, dentures 90 can be used, containing a plurality of prosthetic tooth crowns 70, as seen in Figures 5 A - 5C.
- Braces Other known dental devices include braces for orthodontics.
- Figure 7A illustrates braces 100, which include molar bands 102, arch wires 104, and brackets 106.
- Figure 7B illustrates braces 110, which includes a metal or plastic plate 112, adapted to fit against the roof of the mouth, and wires 114 and 116.
- figure 7C illustrates invisible braces 120.
- Intraoral ambient sensing device US Pat. No. 4,629,424 for a device is disclosed for intraoral ambient sensing.
- the device comprises a removable oral (Hawley) appliance containing a number of chemically sensitive electrodes and a common reference electrode at the chemical sensing sites and a telemetry unit plus power pack for signal transmission.
- This device may also be used to monitor non-chemical parameters, notably pressure, temperature, and flow.
- the removable oral (Hawley) appliance contains a number of sensors to monitor the parameter of interest.
- a pressure sensor configured as an artificial uvula and mounted to the oral (Hawley) appliance emulates actual uvula pressure events.
- a pressure sensor is mounted to the oral (Hawley) appliance in such a manner that it is optimally located at an open bite location of the mouth.
- a telemetry unit mounted to the oral (Hawley) appliance transmits the intraoral ambient information as radio frequency signal bursts.
- a remotely located receiver circuit receives the radio signals which are broadcast and recovers the information encoded in them.
- an exemplary embodiment of the collection device includes a capillary tube capable of receiving or drawing a fluid sample and introducing the fluid sample into the disposable cartridge, a reservoir chamber capable of receiving a fluid sample and a capillary tube holder capable of supporting one end of the capillary tube in the reservoir chamber to draw the fluid sample by capillary action.
- Alternative embodiments of the invention are used in combination with the variety of blood collection assemblies employed by the medical industry to collect fluid samples.
- the methods of the invention may be applied to any characteristic of the mouth and/or pharynx which can be sampled by rinsing and/or gargling, retrieving the resulting fluid in a specified collection container or device and then analyzing the fluid in the collection container or device to provide a rapid or point-of-care result.
- the invention provides methods and a test kit for non-invasive, non-instrumented assessment and diagnosis of the condition of acid reflux by sampling of the pharynx through the gargling process, and rapid determination of the pH of the collected fluid.
- US patents have background relevance to the present invention:
- a device for sampling of oral fluids and blood comprising: a reservoir for collection of the specimens; and an electronic sampling mechanism, the device being adapted for insertion to an oral cavity of a subject.
- the specimens are sampled through a combination of electronic and passive mechanisms.
- the device is adapted to be removably inserted to the oral cavity of the subject.
- the device is adapted to be permanetly inserted to the oral cavity of the subject.
- the device is adapted to be permanently inserted to the oral cavity of the subject, and the device further includes a removable component, which houses at least one of the specimens' reservoir and the power source.
- the electronic sampling mechanism further includes: a control unit, for controlling the sampling rate and timing; an electro-mechanical sampling mechanism, which opens to allow the passage of the fluids, responsive to commands from the control unit; and a power source, for powering the control unit and electro-mechanical sampling mechanism.
- the electro-mechanical sampling mechanism includes a rotor.
- the control unit is selected from the group consisting of a dedicated electronic circuitry, a processor, an ASIC, a microcomputer and discrete components.
- the device for specimens sampling further includes a timing device, selected from the group consisting of a timer, a clock, a calendar, and a combination thereof.
- the device further includes at least one local sensor, integrated with the device.
- the device further includes at least two local sensors, integrated with the device.
- the at least one local sensor is a physiological sensor.
- the local physiological sensor is selected from the group consisting of a sensor for electrolyte concentration in oral fluids, a sensor for glucose concentration in oral fluids, a sensor for a metabolite concentration in oral fluids, a sensor for the pH level in oral fluids, a sensor for the temperature in the oral cavity, a heartbeat sensor, a heart rate sensor, and a snoring sensor.
- the at least one local sensor is a status sensor, for ensuring that the device is in proper operating condition.
- the local status sensor is selected from the group consisting of a sensor for specimen quantity in the reservoir, a sensor for fluid flow rate, a sensor for power source condition, and a sensor for short- circuit detection.
- the device further includes at least one communication component, selected from the group consisting of a receiver, a transmitter, and a transceiver.
- the communication component provides communication with a personal extracorporeal system.
- the personal extracorporeal system is selected from the group consisting of a remote control unit, a computer system, a telephone, a mobile phone, a palmtop, a PDA, a laptop, and a combination thereof.
- the personal extracorporeal system is adapted to provide communication between the device and a monitoring center.
- the communication component provides communication with at least one remote sensor.
- the remote sensor is selected from the group consisting of a sensor for metabolite concentration in oral fluids, a sensor for glucose concentration in the blood and oral fluids, a sensor for a metabolite concentration in the blood, a sensor for an electrolyte concentration in the blood and oral fluids, a sensor for oxygen level in the blood and oral fluids, a sensor for the pH level in the blood and oral fluids, a sensor for glucose concentration in the interstitial fluid, a sensor for a metabolite concentration in the interstitial fluid, a sensor for an electrolyte concentration in the interstitial fluid, a sensor for oxygen level in the interstitial fluid, a sensor for the pH level in the interstitial fluid, a temperature sensor, a heartbeat sensor, a heart rate
- the device further includes at least one fluid, electrolyte and metabolite-transfer component for increased fluid transfer through a biological barrier, by a process selected from the group consisting of iontophoresis, electroosmosis, electrophoresis, electroporation and sonophoresis.
- the specimens sampling mechanism provides the controlled sampling in a manner selected from the group consisting of sampling in accordance with a preprogrammed schedule, sampling at a controlled rate, delayed sampling, pulsatile sampling, chronotherapeutic sampling, closed- loop sampling, responsive to a sensor's input, sampling on demand from a personal extracorporeal system, sampling in accordance with a schedule specified by a personal extraco ⁇ oreal system, sampling on demand from a monitoring center, via a personal extraco ⁇ oreal system, and sampling in accordance with a schedule specified by a monitoring center, via a personal extraco ⁇ oreal system.
- the device further includes at least two specimens' reservoirs.
- each of the at least two specimens reservoirs is controlled independently of the other.
- the device is mounted on a dental implement, designed for the oral cavity of the subject.
- the device is mounted on a clasps attached to a tooth or several teeth, designed for the oral cavity of the subject.
- the dental implement is selected from the group consisting of a prosthetic tooth crown, a dental bridge, a dental three-unit bridge, dental implant, partial dentures, full dentures, braces, a molar band, a night guard, and a mouth guard.
- the device is mounted on an anchor that may be secured to the oral mucosa or the jawbone.
- the device is anchor- free, and is directly implanted into a tissue.
- the device is adapted for buccal sampling.
- the device is adapted for sublingual sampling.
- the device is adapted for labial mucosa sampling.
- the device is adapted for soft-palatal sampling.
- the device is adapted for salivary, crevicular or sputum fluid sampling.
- the device is adapted for oral mucosal specimen sampling.
- the device is adapted for insertion in a mouth of a human.
- the device is adapted for insertion in a mouth of an animal.
- a method of controlled specimen sampling comprising a reservoir containing the collected specimens and an electronic specimen sampling mechanism for controllably sampling the specimens.
- a device for controlled specimens sampling comprising: a reservoir containing the collected specimens; and a dental implement, designed to be inserted to the oral cavity of a subject, and adapted for supporting the specimen reservoir.
- the present invention successfully addresses the shortcomings of the presently known configurations by providing controlled-specimens-sampling oral devices, which are implanted or inserted into an oral cavity, built onto a prosthetic tooth crown, a denture plate, braces, a dental implant, or the like. The devices are replaced as needed.
- the controlled oral specimens sampling may be passive, or electro-mechanically controlled, for a high-precision, intelligent, sampling.
- the controlled sampling may be any one of the following: sampling in accordance with a preprogrammed regimen, sampling at a controlled rate, delayed sampling, pulsatile sampling, chronotherapeutic sampling, closed-loop sampling, responsive to a sensor's input, sampling on demand from a personal extraco ⁇ oreal system, sampling regimen specified by a personal extraco ⁇ oreal system, sampling on demand from a monitoring center, via a personal extraco ⁇ oreal system, and sampling regimen specified by a monitoring center, via a personal extraco ⁇ oreal system.
- Specimen sampling in the oral cavity may be assisted or induced by a transport mechanism, such as any one of, or a combination of iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, and ablation.
- a transport mechanism such as any one of, or a combination of iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, and ablation.
- the oral devices require replacement at different intervals of minutes, hours, days, weeks or months, maintain a desired sampling rate in the oral cavity, for diverse periods, and by being automatic, ensure adherence to a prescribed sampling regimen.
- the oral devices and methods for controlled specimen sampling apply to humans and animals. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
- FIG 1 is a cross-sectional view of a tooth, as known;
- FIGs. 2A - 2G schematically illustrate the steps in root canal therapy, as known;
- FIGs. 3 A - 3F schematically illustrate the application of a dental bridge, as known;
- FIGs. 4A - 4C schematically illustrate the application of a dental implant, as known;
- FIGs. 5A - 5C schematically illustrate the dentures, as known;
- FIGs. 6 A - 6C schematically illustrate the application of a dental crown, as known;
- FIGs. 7A - 7C schematically illustrate the braces, as known;
- FIGs. 8A - 8D schematically illustrate dental bridges, which include devices for specimens sampling, in accordance with preferred embodiments of the present invention;
- FIG. 9 A - 9B schematically illustrate electronic devices for specimens sampling, in accordance with preferred embodiments of the present invention
- FIG. 10 schematically illustrates electro-mechanical specimens sampling mechanisms, operative with the electronic devices for specimens sampling
- FIGs. 11A - 11D schematically illustrate dentures, which include at least one device for specimens sampling, in accordance with another preferred embodiment of the present invention
- FIGs. 12A - 12H schematically illustrate dental braces, which include at least one device for specimens sampling, in accordance with another preferred embodiment of the present invention.
- FIGs. 13 A - K schematically illustrates, which include at least one method for specimens sampling, in accordance with another preferred embodiment of the present invention.
- FIG. 10 schematically illustrates electro-mechanical specimens sampling mechanisms, operative with the electronic devices for specimens sampling
- FIGs. 11A - 11D schematically illustrate dentures, which include at least one device for specimens sampling, in accordance with another preferred embodiment of the present invention
- FIGs. 12A - 12H schematically illustrate
- FIG. 14 schematically illustrates a block diagram, which include at least one method for specimens sampling, in accordance with another preferred embodiment of the present invention.
- FIG. 15 schematically illustrates a block diagram, which include at least one method for specimens sampling, and its extracorporal device for communication, control and data logging and/or controlled drug delivery device in which the delivered dosage is influenced by the sensing mechanism in accordance with another preferred embodiment of the present invention.
- FIG. 16 schematically illustrates an example of the intraoral device shape, which includes at least one method for specimens sampling, in accordance with another preferred embodiment of the present invention.
- the present invention is of oral specimens sampling devices, which are implanted or inserted into an oral cavity, built onto a prosthetic tooth crown, a denture plate, braces, a dental implant, or the like. Specimens sampling may be passive or electro-mechanically controlled, for a high-precision, intelligent sampling.
- specimens sampling may be any one of the following: sampling in accordance with a preprogrammed regimen, sampling at a controlled rate, delayed sampling, pulsatile sampling, chronotherapeutic sampling, closed- loop sampling, responsive to a sensor's input, sampling on demand from a personal extraco ⁇ oreal system, sampling regimen specified by a personal extraco ⁇ oreal system, sampling on demand from a monitoring center, via a personal extraco ⁇ oreal system, and sampling regimen specified by a monitoring center, via a personal extraco ⁇ oreal system.
- Specimens sampling in the oral cavity may be assisted or induced by a transport mechanism, such as any one of, or a combination of iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, and ablation.
- a transport mechanism such as any one of, or a combination of iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, and ablation.
- Figures 8A - 8B schematically illustrate a device 140, for controlled specimens sampling, mounted on a dental bridge 150, in accordance with a preferred embodiment of the present invention.
- dental bridge 150 is removable, constructed in the manner taught in Figures 3E - 3F, hereinbelow.
- Device 140, for controlled specimens sampling is designed as a prosthetic tooth crown 160, and mounted on dental bridge 150, for insertion in the gap between teeth 62 and 64, with clamps 74.
- Prosthetic tooth crown 160 preferably includes a hard outer shell 154, for example, of metal or porcelain, having a coronal side 151 and an apical side 153, wherein the coronal surface is adapted for chewing.
- An inner space of prosthetic tooth crown 160 includes a specimen's reservoir 156, in a dosage form adapted for passive, controlled sampling.
- passive specimens sampling relates to controlled sampling, which is not governed by an electronic device. Passive specimens sampling includes for example, the methods of dosage form preparation described hereinbelow, in items 1 - 14.
- hard outer shell 154 includes at least one, and preferably several perforations 157 for the specimens sampling.
- a semi- pervious membrane 159 may be used, for example on apical side 153.
- one or several perforations 157 and (or) semi-pervious membrane 159 may be operative in the controlled sampling of the specimens.
- the specimens Once placed in the oral cavity, the specimens are sampled in a controlled manner, by a natural phenomenon.
- Two or more dental bridges 150 may be prepared for a patient, in order to maintain a steady sampling of specimens.
- Figures 8C - 8D schematically illustrate a device 142, for passive, controlled specimens sampling, mounted on a three-unit bridge 155, analogous to that taught in Figures 3A - 3D, hereinbelow, in accordance with another preferred embodiment of the present invention.
- the dentist prepares teeth 62 and 64 on either side of a gap by removing portions of the enamel and dentin, leaving stumps 66 and 68. Impressions or molds of stumps 66 and 68 and of the gap between them are taken for the construction of bridge 155.
- three-unit bridge 155 includes device 142, for passive, controlled specimens sampling, designed as a prosthetic tooth crown 165.
- Prosthetic tooth crown 165 has a hard outer shell 161, for example, of metal or porcelain, adapted as a chewing surface.
- Hard outer shell 161 includes a removable component, such as a drawer 167, for refilling, or for replacement.
- Drawer 167 includes specimens' reservoir 156, in a form adapted for passive, controlled sampling, similar, for example, to that of Figures 8A - 8B.
- hard outer shell 161 includes at least one, and preferably several or a plurality of perforations 163 for the specimens sampling, or another manner of opening, for the specimens sampling.
- FIGS 9A - 9C schematically illustrate devices 144 for electronic, controlled specimens sampling, for high-precision, intelligent specimens sampling, in accordance with another preferred embodiment of the present invention.
- device 144 is mounted on a dental bridge 170.
- Dental bridge 170 is preferably, removable, constructed in the manner taught in Figures 3 E - 3 F, hereinbelow.
- Device 144 for electronic, controlled specimens sampling is designed to fit within an inner space of a prosthetic tooth crown 180, for insertion in a gap between teeth 62 and
- dental bridge 170 is adapted for a specific patient.
- Prosthetic tooth crown 180 preferably includes a hard outer shell 174, adapted as a chewing surface.
- the electronics of device 144 may be encased within filler 172, for example, silicon.
- Prosthetic tooth crown 180 includes a specimens reservoir 176, having an orifice controlled by an electro-mechanical sampling mechanism, such as a solenoid 178. It will be appreciated that specimens reservoir 176 may be in a specimens sampling form for a controlled collection, for example, collection at a controlled rate, delayed collection, and (or) pulsatile collection, which may operate in combination with the electronically controlled sampling. It will be appreciated that several specimens' reservoirs 176 may be inco ⁇ orated into a single device 144.
- a specimen's reservoir may contain a different specimen, and each specimen may be collected independently, in accordance with a different regimen.
- a power source 182 provides prosthetic tooth crown 180 with power.
- a control unit 184 controls the operation of electro-mechanical sampling mechanism 178, for the collection of specimens to the oral cavity and (or) oral tissue, in a controlled manner.
- Control unit 184 may be any one of a dedicated control circuitry 184, a processor 184, an Application Specific Integrated Circuit (ASIC) 184, or a microcomputer 184, as known, and may further include built-in intelligence.
- a memory unit 186 may be integrated with it. It will be appreciated that control unit 184 may control both the timing for specimens sampling and the sampling rate.
- power source 182 may be any power source, for example, a battery or a solid-electrolyte fuel cell.
- control unit 184 has a built-in timing device, which preferably includes a timer, a clock and a calendar, and is operative to perform chronotherapy.
- a receiver 188 which may further operate as a transceiver, provides communication with a personal extraco ⁇ oreal system 208, for example, as described in conjunction with Figures 13A - 13K, hereinbelow. It will be appreciated that a separate transmitter may be used.
- Transceiver 188 may operate by RF, IR or ultrasound. It may further utilize any one of Bluetooth, Wi-Fi, W-LAN, 802.11, CDMA, GSM protocols.
- device 144 for electrically controlled specimens sampling may further include at least one specimens-transfer component for increased specimens transfer through a biological barrier, to enhance buccal, sublingual, labial mucosa and soft-palatal direct sampling.
- the specimens transfer mechanism may include iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, ablation.
- the at least one specimens-transfer component may be, for example, at least one electrode or several electrodes, for an electrotransport mechanism including electric ablation, an ultrasound transducer, for sonophoresis, a microwave coil, for microwave ablation, an RF coil, for RF ablation, or a laser diode, for laser ablation, as known. Additionally, a combination of these may be employed. These mechanisms may be controlled by control unit 184. Additionally or alternatively, they may be controlled remotely, by personal extraco ⁇ oreal system 208 ( Figures 13A - 13K), such as remote- control unit 190, computer system 200, telephone 202, mobile phone 206, palmtop 207, laptop 209, or any other remote-control unit, as known.
- Device 144 may further include at least one and preferably several sensors 185, inco ⁇ orated to device, and thus termed "local sensors," to distinguish them from remote sensors, located elsewhere in the body.
- Local sensors 185 may be divided into two groups: i. physiological sensors 185, for measuring, for example, an analyte concentration in the saliva, glucose concentration in the saliva, a metabolite concentration in the saliva, an electrolyte concentration in the saliva, the pH level in the saliva, a concentration level of food, alcohol, or tobacco, the temperature in the oral cavity, and any other physiological parameter or parameters, preferably having a bearing on the specimens sampling schedule; and ii.
- Physiological sensor 185 may be, for example, an electrochemical glucose sensor, such as a enzymatic biosensor taught in www.cfdrc.com/applications/biotechnology/biosensor.html, which utilizes the biospecificity of an enzymatic reaction, along with an electrode reaction that generates an electric current or a potential difference for quantitative analysis.
- the enzymatic oxidation of glucose produces hydrogen peroxide, which in turn generates electrons by electrode reaction.
- the current density is used as a measure of glucose in a sample, for example, in interstitial fluid. Additionally or alternatively, glucose levels may be monitored for example, as taught by US Patent 6,201,980, to Darrow, et al., dated March 13, 2001, entitled, 'Implantable medical sensor system," whose disclosure is inco ⁇ orated herein by reference.
- Darrow, et al. disclose an implantable chemical sensor system for medical applications, which permits selective recognition of an analyte using an expandable biocompatible sensor, such as a polymer, that undergoes a dimensional change in the presence of the analyte.
- the expandable polymer is inco ⁇ orated into an electronic circuit component that changes its properties (e.g., frequency) when the polymer changes dimension.
- an external interrogator transmits a signal transdermally to the transducer, and the concentration of the analyte is determined from the measured changes in the circuit.
- the implantable chemical sensor system may be used for minimally invasive monitoring of blood glucose levels or interstitial fluid glucose levels in diabetic patients.
- physiological sensors 185 may be, for example, as taught by US Patent 6,058,331, to King, dated May 2, 2000, and entitled, "Apparatus and method for treating peripheral vascular disease and organ ischemia by electrical stimulation with closed loop feedback control," whose disclosure is inco ⁇ orated herein by reference.
- King discloses techniques for therapeutically treating peripheral vascular disease, wherein a sensor is employed for sensing the extent of blood flow in a patient's limb or ischemic pain and generating a response, based on the sensor's reading.
- physiological sensors 185 may be based on Ambri's Ion Channel
- ICSTM Ambri Ion Channel Switch
- sensors of different types may be used.
- Device 144 may further include at least one, and preferably several remote physiological sensors 185, implanted or otherwise placed elsewhere in the body, each having its own power supply and transmitter or transceiver.
- a remote sensor module 185 of several physiological sensors may be employed, wherein the several sensors share a power supply, a transmitter or transceiver, and possibly a control unit.
- the remote sensor module may further include a remote status sensor 185, for reporting the remote-sensor power source condition.
- Examples of remote physiological sensors 185 may include a sensor for analyte concentration in the blood, a sensor for glucose concentration in the blood, a sensor for a metabolite concentration in the blood, a sensor for an electrolyte concentration in the blood, a sensor for oxygen level in the blood, a sensor for the pH level in the blood, a sensor for alcohol level in the blood, a sensor for specimens concentration in the interstitial fluid, a sensor for glucose concentration in the interstitial fluid, a sensor for a metabolite concentration in the interstitial fluid, a sensor for an electrolyte concentration in the interstitial fluid, a sensor for oxygen level in the interstitial fluid, a sensor for the pH level in the interstitial fluid, a sensor for alcohol level in the blood, a sensor for specimens concentration in the sweat, a temperature sensor, a heartbeat sensor, a blood pressure sensor, a heart rate sensor, and a snoring sensor.
- Remote sensors 185 may be intraco ⁇ oreal, implanted under the skin, for example, in the chest or under the arm, for measuring, for example, interstitial fluid specimens' concentration level, interstitial fluid glucose level, tissue temperature, blood pressure, and heart rate. Additionally or alternatively, remote sensors 185 may be intraco ⁇ oreal, implanted on stents, in blood vessels, for measuring, for example, blood specimens' concentration level, blood glucose level, or blood oxygen level. Additionally or alternatively, remote sensors 185 may be extraco ⁇ oreal, for example, attached to the skin.
- the extraco ⁇ oreal sensors may include piezoelectric patches that may be attached to the skin, by adhesives, for measuring heart rate, patches for measuring body temperature, and (or) sensors that measure concentration levels of the specimens, or of other chemicals, such as glucose, in the sweat.
- extraco ⁇ oreal, remote sensors 185 may be similar to those taught by Lin, G., and Tang, W., "Wearable Sensor Patches for Physiological Monitoring," NASA's Jet Propulsion Laboratory, Pasadena, California, which may be found at www.nasatech.com/Briefs/Feb00/NPO20651.html, or in NASA Tech Briefs: NPO-20651, which may be obtained from Technology Reporting Office, JPL, Mail Stop 122-116, 4800 Oak Grove Drive, Pasadena, CA 91109, (818) 354-2240.
- the wearable sensor patches formed as miniature biotelemetric units, may be employed for measuring temperature, heart rate, blood pressure, and possibly other physiological parameters.
- the sensor patches are designed small and may be mass-produced inexpensively by use of state-of-the-art techniques for batch fabrication of integrated circuits and microelectromechanical systems.
- Each patch may be a few centimeters on a side, comparable in size to an ordinary adhesive bandage.
- the patch may even be held on the wearer's skin by the same adhesive as that used on bandages.
- the patch may contain a noninvasive microelectromechanical sensor integrated with electronic circuitry operative to process the sensor output and transmit a radio signal modulated by the processed sensor output.
- a plurality of miniature sensors of a same type may be employed, to increase the accuracy of the measurements. Additionally or alternatively, sensors of different types may be used.
- sensor modules 185 may be used, at different locations in the body. Communication between remote sensors 185 and prosthetic tooth crown 180 of device 144 is preferably by ultrasound, but may be by IR or RF, and may employ communication protocols, such as any one of Bluetooth, Wi-Fi, W-LAN, 802.11, CDMA, RFID, GSM protocols. It will be appreciated that other protocols may also be used. Additionally or alternatively, remote sensors 185 may communicate with one or more personal extraco ⁇ oreal systems 208, as described in conjunction with Figures 13 A - 13K, hereinbelow, preferably by IR or RF, and may employ communication protocols, such as any one of Bluetooth, Wi-Fi, W-LAN, 802.11, CDMA, RFID, GSM protocols.
- Communication may be on a continuous basis, at intervals, in reply to interrogation, or when a sudden change in a measured physiological parameter is observed.
- the remote sensors do not have power sources, but respond to interrogation, which further provides them with power for measuring and responding, as known, for example, as described in any one of U.S. Patent Application No.
- prosthetic tooth crown 180 may also be designed on a three-unit bridge, in a manner analogous to prosthetic tooth crown 165 of Figures 8C - 8D, wherein parts that need replacement, such as specimens reservoir 176 and possibly also power source 182 are located in a drawer, analogous to drawer 167 there.
- device 144 for electronic, controlled specimens sampling is designed as a dental-implant-and-prosthetic-tooth-crown 210.
- Device 144 for electronic, controlled specimens sampling has a permanent portion 220, located in the post and a removable portion 230, in the crown.
- Removable portion 230 in the crown of device 144, includes a specimen's reservoir 216, whose specimens sampling is controlled by an electro-mechanical sampling mechanism 218.
- a power source 222 provides power. These are encased within filler 212, for example silicon.
- a hard shell 214 provides the chewing surface. Preferably, impressions have been taken so that removable portion 230 is adapted for a specific patient. Additionally, two or more removable portions 230 may be made, so that one is in operation while the other is being refilled.
- Permanent portion 220, in the post may include a control unit 224, such as a processor 224, for controlling the operation of electro-mechanical sampling mechanism 218, preferably also a memory unit 226, and a transmitter-receiver 228.
- At least one sensor 215 may be located on the interface between the post and the crown, and may be attached to either. Alternatively, at least one sensor 215 may be located within the post or within the crown. Alternatively, the sensor or sensors may be located elsewhere in the body. Electro-mechanical sampling mechanism 218 may be located in the post or in the crown of device 144.
- the operation of the present embodiment is similar to that of the embodiment of Figures 9A - 9B, save for the advantage that only the portions of the electronic device that need replacement, namely the specimens reservoir and the power source, are adapted for removing. It will be appreciated that a similar construction of a permanent portion and a removable portion may be used in conjunction with a root canal ( Figures 2 A - 2G).
- the permanent portion may be located in the canal, and the removable portion may be located in the crown.
- the crown of device 144 may also be designed in a manner analogous to prosthetic tooth crown 165 of Figures 8C - 8D, wherein parts that need replacement, such as specimens reservoir 176 and possibly also power source 182 are located in a drawer, analogous to drawer 167 there.
- Figures 10A - 10F schematically illustrate electro-mechanical sampling mechanisms 178, operative with the electronic devices for controlled specimens sampling of FIGs. 9A - 9C, in accordance with embodiments of the present invention.
- electro-mechanical sampling mechanism 178 may be designed as a Vane engine 175 A, having a housing 171, a rotor 173, an inlet 177 and an outlet 179, wherein inlet 177 is in communication with specimens' reservoir 176, and outlet 179 leads to the oral cavity.
- inlet 177 opens, allowing specimens from specimens' reservoir 176 to enter an inner cavity 141 of engine 175A, and be pushed out through outlet 179.
- inner cavity 141 may be designed so as to avoid specimens compression during the cycle.
- Device 144 for • electronic, controlled specimens sampling may include one or several specimens' reservoirs 176, each in communication with one inlet 177 and one rotor arrangement.
- Control unit 184 ( Figures 9A - 9C) may translate the amount of specimens to be collected into specimens reservoir 176 to a number of rotor revolutions, so that, with each revolution, a predetermined amount of specimens is issued to the specimens reservoir and collected from the oral cavity.
- Figures 11 A - 1 ID schematically illustrate full dentures, which include at least one device for controlled specimens sampling, in accordance with another preferred embodiment of the present invention. It will be appreciated that partial dentures may similarly be used.
- dentures 240 includes a plurality of prosthetic tooth crowns 70, as taught in conjunction with Figures 5A - 5C, hereinbelow. Additionally, dentures 240 include a device 148 for controlled specimens sampling, designed as a prosthetic tooth crown 242. Prosthetic tooth crown 242 may be adapted for passive controlled specimens sampling, as taught in conjunction with Figures 8A - 8D.
- prosthetic tooth crown 242 may be adapted for electronically controlled specimens sampling, as taught in conjunction with Figures 9 A - 9B, and preferably operate with any one of or a combination of personal extraco ⁇ oreal systems 208, described hereinbelow, in conjunction with Figures 13A - 13K, and with a monitoring center 500 described hereinbelow, in conjunction with Figure 13G.
- dentures 250 includes a plurality of prosthetic tooth crown 70, as taught in conjunction with Figures 5A - 5C, hereinbelow. Additionally, dentures 250 include devices 147 and 149, designed as prosthetic tooth crowns 252 and 254, for controlled specimens sampling.
- prosthetic tooth crowns 252 and 254 may form a single device for electronically controlled specimens sampling, wherein prosthetic tooth crown 252 may form a removable portion, which includes the specimens reservoir and power source, which must be replaced periodically, while prosthetic tooth crown 254 may include the permanent components, as taught in conjunction with Figure 10, hereinbelow.
- Figures 11C and 11D illustrate front and back sides of full dentures 260, which include a plate 264, which may be fitted under the tongue, for bottom dentures, or against the roof of the mouth, for top dentures.
- the backside ( Figure 11D) further includes a device 262, for controlled specimens sampling. In this manner, soft-palatal and (or) sublingual, labial mucosa and buccal administration may be enhanced.
- FIG. 12A - 12H schematically illustrate dental braces, which include at least one device for controlled specimens sampling, in accordance with another preferred embodiment of the present invention. While Figure 12A schematically illustrates conventional braces 100, having molar bands 102, as taught in conjunction with Figure 7 A, hereinbelow, Figures 12B illustrates braces 270, which include a device 272 for controlled specimens sampling, in accordance with a preferred embodiment of the present invention. Device 272 is attached to molar bands 102 with wires 276. Additionally, Figure 12C illustrates braces 280, which include devices 282 and
- Devices 282 and 284 are attached to molar bands 102 with wires 286.
- Figures 12D illustrates an arrangement 290, in which a device 292 for controlled specimens sampling is attached to a molar band 298, with wires 296, in accordance with a preferred embodiment of the present invention.
- Figure 12E schematically illustrates conventional braces 110, having a plate
- Figures 12F illustrates braces 300, which include a device 302 for controlled specimens sampling, arranged on the back side of plate 112, in accordance with a preferred embodiment of the present invention.
- device 302 is adapted for enhanced buccal and sublingual administration.
- Figure 12G schematically illustrates conventional invisible braces 120, as taught in conjunction with Figure 7C, hereinbelow
- Figures 12H illustrates braces 310, which include a device 312 for controlled specimens sampling, arranged on an added invisible portion 314.
- a mouth guard or a night guard may be used, for attaching a device for controlled specimens sampling.
- Devices 272, 282, 284, 292, 302 and 312 for controlled specimens sampling may be passive or electronically controlled.
- a dentist may examine the mouth of the person. If the patient has a dental implement, such as a crown, a prosthetic tooth crown, a bridge, dentures, braces, a night guard or a mouth guard, any one of these may be replaced with devices in accordance with the present invention.
- the patient may be in need of a dental implement, such as a crown, a prosthetic tooth crown, a bridge, dentures, braces, a night guard or a mouth guard, the needed implement may be prepared so as to include a device in accordance with the present invention.
- a wisdom tooth may be missing either because it has not yet emerged, or because it has been extracted, and that space may be used for a device in accordance with the present invention, for example, attached to a molar band, as taught in conjunction with Figure 12D.
- a device may be mounted on a braces plate, even where braces need not be used, for dental reasons, as taught in conjunction with Figure 12F.
- a device may be mounted on a night guard or a mouth guard, even where it need not be used for dental reasons. It will be appreciated that a combination of the above may be used.
- Figure 14 depicts a typical system block diagram. The final device may exclude some blocks or include any combination thereof.
- Device 801 - generates a vacuum in the samples accumulation chamber directing the flow inwards toward the chamber.
- Device 802 includes an add-on hyd ⁇ philic substance to assist in the direction and accumulation of fluids toward the chamber.
- Device 803 a power source, batteries (primary, secondary, paper type).
- Device 804 the electronic based control module based on a microprocessor, ASIC, discrete ICs or any combination thereof.
- Device 805 communication module for bi-directional or uni-directional communication from the device to the extraporal devices. Communication is based on Infra Red or radio frequency using proprietary protocol or standard protocol like Bluetooth, WiFi, RFID or combination thereof.
- Device 806 - reverse iontophoresis applies electrical current to the intraoral tissue.
- Device 807 - reverse RF microchanneling creates an array of microchannels in the tissue by applying an RF energy.
- Device 808 - reverse sonophoresis - increase the permeability of the tissue by applying a low frequency (20KHz to 3MHz) over the tissue.
- Device 809 includes tissue permeability enhancers chemicals.
- Item 810 represents the intraoral tissue itself, gingival, buccal, mucosa, sublingual, palate or any combination thereof.
- Device 811 represents the chamber that accumulate the extracted fluids and substances to be analyzed locally or by external device.
- Device 812 includes interconnecting bus connecting electronically and mechanicallys the various devices comprising the final element.
- Figure 15 depicts the basic system block diagram. The final device may exclude some blocks or include any combination thereof.
- Device 852 is the sample analyzer, analyzing the samples and measure its components in a quantified manner.
- Device 853 - a controlled drug delivery device that releases and delivers the selected drugs in a controlled manner in accordance with the sample sensing results.
- Device 854 - an extraporal device to receive, log, control and communicate with the intraoral sensors. It will be appreciated that the electronic device for controlled specimens sampling may be mounted on any anchor that may be secured to the oral mucosa or the jawbone.
- the electronic device for controlled specimens sampling may be directly implanted into a tissue without a specific anchoring element.
- Figure 16 depicts an example of the proposed device.
- Sub-module 871 is the sampling reservoir.
- Sub-module 872 are the electrophoresis electrodes.
- Sub-module 873 inlets for sampled specimens.
- Sub-module 874 the clasps attached to the teeth.
- Other elements such as power supply, electronics, communication are embedded inside the device.
- the inlet opening is facing the buccal tissue and touching it as the mouth is close. The device can be easily inserted or removed. .
- the device for controlled specimens sampling may be implanted or inserted in animals, such as pets, for example, dogs, and cats, farm stock, such as sheep, goats, cows, horses, pigs, and the like, or fowl, such as chickens, ducks, geese, turkeys, and other fowl.
- animals such as pets, for example, dogs, and cats, farm stock, such as sheep, goats, cows, horses, pigs, and the like, or fowl, such as chickens, ducks, geese, turkeys, and other fowl.
- EXAMPLE 1 - Passive, Controlled specimen sampling Device 140 designed as prosthetic tooth crown 160 ( Figures 8 A - 8B) for passive, controlled specimen sampling, or another device for passive, controlled specimen sampling may include specimen reservoir 156 and a semi-permeable membrane, which is formed of hydrophobic polymers, such as cellulose acetate, or ethocel, mixed with water soluble additives, such as sugar, PEG'S, and the like. Upon collection, the soluble additives dissolve and a semipermeable membrane is created.
- a semi-permeable membrane which is formed of hydrophobic polymers, such as cellulose acetate, or ethocel, mixed with water soluble additives, such as sugar, PEG'S, and the like.
- EXAMPLE 2 - Delayed, Passive, Controlled specimen sampling Device 140 designed as prosthetic tooth crown 160 ( Figures 8 A - 8B) for passive, controlled specimen sampling, or another device for passive, controlled specimen sampling may include several specimen reservoirs 156, wherein a first reservoir is adapted for passive, controlled delivery, for example, by diffusion and erosion, and a second specimen reservoir, which is coated by a special functional coating, designed to halt the sampling into the second reservoir until the first reservoir is full. In this manner, the interval between replacements may be extended.
- EXAMPLE 3 Pulsatile, Passive, Controlled specimen sampling Device 140, designed as prosthetic tooth crown 160 ( Figures 8 A - 8B) for passive, controlled specimen sampling, or another device for passive, controlled specimen sampling may include a specimen reservoir 156, which includes a multi-layer coating, designed for pulsatile passive controlled sampling, which may be synchronized, for example, with circadian cycles, for a desired chronotherapy.
- EXAMPLE 4 Passive, Controlled specimen sampling
- Prosthetic tooth crown 160 ( Figures 8 A - 8B) for passive, controlled specimen sampling, or another device for passive, controlled specimen sampling may include specimen reservoir 156 specimens, inco ⁇ orated into pellets or minitabs. The collection mechanism is diffusion or erosion. The specimens are replaced once a week.
- EXAMPLE 5 Electronic and Passive Controlled specimen sampling
- Electronic, controlled specimen sampling device 460 may include two or more specimen reservoirs, such as 411 A, 411 B, and 411C of specimens, inco ⁇ orated into pellets or minitablets, of a passive, controlled collection, which may last varying periods of time.
- electro-mechanical sampling mechanism 416 opens first specimen reservoir 411 A, and controlled collection by diffusion takes place.
- status sensor 412B informs control unit 410, and control unit 410 instructs electro-mechanical sampling mechanism 416 to open second specimen reservoir 41 IB. After a certain period of time, second reservoir is full, and third specimen reservoir 411C is opened.
- EXAMPLE 6 Electromechanically Controlled specimen sampling
- Device 144 ( Figures 9 A - 9C) for electronic, controlled specimen sampling may include one or several specimen reservoirs
- Control unit 176 each in communication with one inlet 177 and one rotor arrangement.
- Figures 9A - 9C may translate the amount of specimen to be sampled into specimen reservoir 176 to a number of rotor revolutions, so that, with each revolution, a predetermined amount of specimen is issued into the specimen reservoir and collected from the oral cavity.
- EAMPLE 7 Controlled specimen sampling for Buccal, Sublingual, Labial Mucosa, and Soft-Palatal collection, with a Transport Mechanism
- the present invention is adapted for specimen abso ⁇ tion from any one of buccal, sublingual, labial mucosa, and (or) soft-palatal sites, which may be further assisted by a mechanism for increased specimen transfer through the biological barrier, for example, by a mechanism such as reverse iontophoresis, electroosmosis, electrophoresis, electroporation, sonophoresis, ablation and RF micro-channeling.
- device 144 (figures 9 A - 9C) for electrically controlled specimen sampling may include at least one specimen-transfer component for increased specimen transfer through a biological barrier.
- the location of the device for controlled specimen sampling may determine the main collection route.
- sublingual and labial mucosa specimen abso ⁇ tion may be achieved by placing the device for controlled specimen sampling on a bottom-denture plate ( Figures 11C - 11D), or on a bottom-braces place (Figure 12F), or on a bottom plate of a night guard or a mouth guard;
- soft-palatal specimen abso ⁇ tion may be achieved by placing the device for controlled specimen sampling on a top-denture plate ( Figures 11C - 1 ID), or on a top-braces place (Figure 12F), or on a top plate of a night guard or a mouth guard;
- buccal specimen abso ⁇ tion may be achieved by placing the device for controlled specimen sampling on a prosthetic tooth crown, ( Figures 8A - 8D).
- a transport mechanism for example, iontophoresis may be inco ⁇ orated.
- two biocompatible electrodes may be placed against the buccal tissue, for applying a current of up to 0.5 mA to the buccal surface.
- the current may be applied in pulses, which may vary by time, or modulating frequency, or as a DC current.
- the transfer tissue may be any one of sublingual, labial mucosa, and (or) soft-palatal tissue.
- another transport mechanism for example, sonophoresis may be used.
- a piezoelectric tranducer may be placed against any one of the buccal, sublingual, labial mucosa, and (or) soft-palatal tissue, and adapted to resonate at a frequency of between 20KHz and 1.5Mhz. Additionally, the resonation may vary in power, frequency, modulation, duration and pulse width.
- EXAMPLE 8 Controlled specimen sampling for Veterinary Use
- controlled monitoring by devices implanted in the mouth cavities of the cows, may be used, to be informed that the plurality of cows ovulate at about the same time, for breeding management. It will be appreciated that many other veterinary uses are possible.
- any one of device 400, 440, 450, or 460, for electronic, controlled specimen sampling to synchronize the therapy may be pre-programmed for clock operated specimen sampling, for example, of chemotherapy, for chronotherapy.
- specimen sampling may be synchronized with either predetermined patterns or real-time measurements of physiological parameters.
- the cancer patient will receive the cancer drugs in an effective way, with minimal side effects and waste.
- chronotherapy may be useful in the treatment of arthritis. People with osteoarthritis tend to have less pain in the morning and more at night; while those with rheumatoid arthritis, have pain that usually peaks in the morning and decreases throughout the day. Chronotherapy for all forms of arthritis using
- NSAIDs such as ibuprofen may be timed to ensure that the highest blood levels of the drug coincide with peak pain.
- Devices 400 or 460, for electronic, controlled specimen sampling ( Figures 14A and 14D), may be pre-programmed for clock-operated specimen sampling, synchronized to the circadian rhythm of the disease, based on the patient's history, for chronotherapy.
- Chronotherapy may be supplemented by remote control operation, from personal extraco ⁇ oreal system 420, preferably by the patient, for example, from remote-control unit 402, palmtop 407, or another remote-control unit, when a patient feels pain.
- Specimen sampling for Diabetes Glucose levels vary throughout the day, to some extent in a cyclic manner. Additionally, there is a rise in glucose level shortly after eating.
- Devices 400 or 460, for electronic, controlled specimen sampling may be pre- programmed for clock operated specimen sampling, synchronized to the circadian rhythm of the glucose, for chronotherapy. Preferably, the synchronization is based on the patient's history of glucose level cyclic variations.
- Chronotherapy may be supplemented by remote control operation, from personal extraco ⁇ oreal system 420, preferably by the patient, for example, from remote-control unit 402, palmtop 407, or another remote-control unit, when a patient is about to eat, since he knows that glucose levels will rise then.
- remote control operation may be performed, responsive to a report from one or several sensors 413, that glucose levels in the blood or in the interstitial fluid have risen.
- the remote control operation from personal extraco ⁇ oreal system 420, may be by the patient, for example, from remote- control unit 402 or palmtop unit 407, upon the patient's seeing the glucose level measurement on display. Additionally or alternatively the patient may forward the measurement to monitoring center, for example, via remote-control unit 402 or palmtop unit 407, or another remote-control unit, for the monitoring center's decision, for example of computer , on a specimen sampling schedule.
- chronotherapy may be useful in the treatment of asthma, since asthmatic patients tend to have attacks during the early hours of the morning, for example, between 3 and 5 AM.
- Devices 400 or 460, for electronic, controlled specimen sampling may be pre-programmed for clock operated specimen sampling, synchronized to the circadian rhythm of the disease, for chronotherapy, which at times may be further supplemented by remote control operation. Synchronization may be performed on a case by case basis, by preprogramming the device, based on the patient history of the disease. Additionally or alternatively, the specimen sampling rate may be increased a little before the expected time for the attack.
- Chronotherapy may be supplemented by remote control operation, from personal extraco ⁇ oreal system 420, preferably by the patient, for example, from remote-control unit 402 or palmtop unit 407, or another remote-control unit, when a patient feels the onset of an attack.
- EXAMPLE 13 Sensor- Activated Specimen sampling for Snoring and other Sleeping Disorders
- Sensors 412 may be piezo-electric transducers, which sense sound, such as snoring, or heartbeat. The determination and demand for monitoring may be made directly by control unit 410, based on its built-in intelligence and algorithms, for monitoring responsive to the communicated measurements.
- the communicated measurement may be the sound of snoring.
- the communicated measurement may be the rate of heartbeat, indicating whether the patient is asleep or awake.
- EXAMPLE 14 - Remote Control Specimen sampling for Mental Diseases Devices 400 or 460, for electronic, controlled specimen sampling may be used by patients suffering from mental conditions such as depression or hypertension. When the situation deteriorates, either the patient, or a caretaker such as a parent may initiate specimen sampling, for example, via remote-control unit 202, palmtop
- sensors 412 or 413 may further include a global positioning device, and these may also be mounted on remote-control unit 202, and (or) palmtop 407, or another remote-control unit, for reporting both the location of the patient and of the remote-control unit to the monitoring center.
- EXAMPLE 15 - Sexual Dysfunction Devices 400 or 460 for electronic, controlled hormonal monitoring may be used for sexual dysfunction, wherein when wishing to be aroused, a person uses remote-control unit 402 or palmtop 407, or another remote-control unit, for monitoring.
- EXAMPLE 16 Narcotic Rehabilitation When using device 400 or 460, having status sensors, to determine and report the amount of specimen remaining in the specimen reservoir, for example, on display on remote-control unit 402 or palmtop 407, or another remote-control unit, the user may observe and actively participate in the specimen sampling rate.
- EXAMPLE 17 Taking blood samples from people with mental disturbance
- Anorexia Nervosa is defined as a serious, potentially life-threatening eating disorder characterized by self-starvation and excessive weight loss.
- Conventional, orally administered specimen treatment may include citalopram (Selective Serotonin Reuptake
- an oral device for controlled specimen sampling and a method for controlled specimen sampling may be applied in conjuction with the treatment.
- Bulimia Nervosa is defined as a serious, potentially life-threatening eating disorder, characterized by a cycle of bingeing and compensatory behaviors such as self- induced vomiting designed to undo or compensate for the effects of binge eating.
- Conventional, orally administered drug treatment may include Fluoxetine (60 mg/day).
- an oral device for controlled specimen sampling and a method for controlled specimen sampling may be applied.
- the controlled sampling rate which aims at maintaining a substantially constant specimen concentration in the blood by proper drug delivery, may be more effective at preventing binges and purges, then conventional, orally administered drug.
- the ability to program the oral device for controlled specimen sampling for chronotherapeutic delivery may be applied, to program the device functioning according to the known times of binges, or of purges. 3.
- Obesity, or overweight are conventionally treated by L-tryptophan (essential amino acid, 1 - 3 g administered 1 h before a plated meal), Sibutramine (serotonin- noradrenaline reuptake inhibitor, 10-20 mg daily), and (or) bitter substances like nicotine.
- L-tryptophan essential amino acid, 1 - 3 g administered 1 h before a plated meal
- Sibutramine sibutramine (serotonin- noradrenaline reuptake inhibitor, 10-20 mg daily)
- bitter substances like nicotine in accordance with the present invention, an oral device for controlled specimen sampling and a method for controlled specimen sampling, as taught in conjunction with any one of Figures 8 A - 14D may be applied, with advantages similar to those cited in item (2). 4.
- Binge Eating Disorder and (or) Compulsive Overeating relate to any one of the following: i. eating in a manner which is out of control; ii. eating an unusually large amount of food;
- Binge eating disorder is conventionally treated with antidepressants, and zonisamide (antiepileptic drug, 100-600 mg/day).
- an oral device for controlled specimen sampling and a method for controlled specimen sampling as taught in conjunction with any one of Figures 8 A - 14D may be applied, with advantages similar to those cited in item (2). 5.
- Eating Disorders Not Otherwise Specified which are defined as variants of anorexia nervosa or bulimia nervosa, as they do not meet the diagnostic criteria for anorexia nervosa or bulimia nervosa, but require treatment, nonetheless. Examples include women who would meet the criteria for anorexia nervosa, save for the fact that they continue to menstruate, individuals who regularly purge but do not binge eat, and individuals who nearly meet criteria for bulimia nervosa, but binge eat less than twice a week. EDNOS can be a serious, potentially life-threatening eating disorder.
- an oral device for controlled specimen sampling and a method for controlled specimen sampling may be applied, with advantages similar to those cited in item (2).
- an oral device for controlled specimen sampling smoke sensing and a method for controlled specimen sampling and smoke sensing may be used for providing a controlled dose of nicotine or bupropion hydrochloride to assist a person trying to quit smoking.
- a desired level of bupropion hydrochloride in the blood stream may be achieved and the noradrenergic and dopaminergic pathways in the brain are stimulated.
- the sense of boredom and latency which causes people to light a cigarette, is satiated by bupropion hydrochloride.
- EAMPLE 20 - Treatment of Alcoholism Conventional treatment of alcohol may use, for example, orally administered ondansetron
- an oral device for controlled specimen sampling and a method for controlled specimen sampling may be used for providing a controlled dose of ondansetron to assist a person trying to overcome a dependence on alcohol.
- EXAMPLE 21 Bad Breath Treatment Anearobic bacteria on the surface of tongue and the throat cause bad breath, by breaking down proteins at a very high rate.
- a controlled treatment regimen may include a controlled delivery of any one of 0.2% chlorhexidine solution, chlorhexidin 0.05% plus etylpyridinium chloride 0.05% plus zinc lactate 0.14%, Zinc Gluconate, OXYD-8, or a mint flavoring.
- EAMPLE 22 - Personalized Specimen Collection Based on DNA Analysis Specimen sampling schedule may be based on DNA reconstruction and analysis, to match each patient's DNA. DNA parameters may be processed prior to the specimen collection, or during it, to define the best specimen collection policy for a particular patient.
- A-DNA dependent delivery schedule may occur, for example, in consequence to a determination that the patient's DNA includes a gene that makes that patient more susceptible to certain diseases, such as, breast cancer, or heart attacks.
- EAMPLE 23 - Personalized Specimen Collection Based on physical parameters and personal history Specimen sampling schedule may be based on physical-parameters and personal- history analyses, so as to be tuned to a specific patient.
- Physical-parameters and personal- history analyses may include patient's weight, height, age, gender, physiological history, medical status, other medication administrated simultaneously, blood pressure, blood analysis and the like. These parameters may be processed prior to the specimen collection, or during it, to define the specimen collection policy that will achieve best results for a particular patient.
- the buccal epithelium is similar in structure to other stratified epithelia of the body, and enhancers used to improve specimen permeation in other abso ⁇ tive mucosae have been shown to work in improving buccal specimen penetration as well. (Shojaei, A.
- permeation enhancer examples include 23-lauryl ether, Aprotinin, Azone, Benzalkonium chloride, Cetylpyridinium chloride,
- EDTA Sodium glycocholate, Sodium glycodeoxycholate, Sodium lauryl sulfate, Sodium salicylate, Sodium taurocholate, Sodium taurodeoxycholate, Sulfoxides.
- Various alkyl glycosides It is expected that during the life of this patent many relevant oral devices and methods of controlled specimen sampling will be developed and the scope of these terms is intended to include all such new technologies a priori.
- the term "about” refers to ⁇ 30 %. Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting.
- EAMPLE 25 - Veterinary use A device similar to a device shown in figure 16, and adopted to the specific animal oral structure can be placed inside the animal oral cavity monitoring the animal health in a timely and fully controlled manner. The results are logged inside the device built-in memory and/or transmitted in real-time to the farmer's supervising center.
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Abstract
Description
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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EP05743964A EP1765150A2 (en) | 2004-05-27 | 2005-05-26 | Intraoral apparatus and method for blood and saliva monitoring & sensing |
US11/603,897 US20070106138A1 (en) | 2005-05-26 | 2006-11-24 | Intraoral apparatus for non-invasive blood and saliva monitoring & sensing |
Applications Claiming Priority (2)
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US60/574,562 | 2004-05-27 |
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US11/603,897 Continuation-In-Part US20070106138A1 (en) | 2005-05-26 | 2006-11-24 | Intraoral apparatus for non-invasive blood and saliva monitoring & sensing |
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WO2005115225A2 true WO2005115225A2 (en) | 2005-12-08 |
WO2005115225A3 WO2005115225A3 (en) | 2006-04-13 |
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PCT/IL2005/000542 WO2005115225A2 (en) | 2004-05-27 | 2005-05-26 | Intraoral apparatus and method for blood and saliva monitoring & sensing |
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Cited By (10)
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WO2013049327A2 (en) * | 2011-09-28 | 2013-04-04 | University Of Florida Research Foundation, Inc. | Multifunctional oral prosthetic system |
CN105148734A (en) * | 2015-08-28 | 2015-12-16 | 安徽中烟工业有限责任公司 | Selective regulation method of ammonium ion in papermaking method reproduced tobacco leaf extract liquor |
WO2017054396A1 (en) * | 2015-09-29 | 2017-04-06 | 京东方科技集团股份有限公司 | Intelligent tooth jewellery and usage method thereof |
US10058283B2 (en) | 2016-04-06 | 2018-08-28 | At&T Intellectual Property I, L.P. | Determining food identities with intra-oral spectrometer devices |
EP2259714B1 (en) * | 2008-02-22 | 2019-09-11 | NanoMed Diagnostics B.V. | Device for detecting a medical condition or disease |
US10517525B2 (en) | 2013-01-14 | 2019-12-31 | University Of Florida Research Foundation, Inc. | Smart diagnostic mouth guard system |
US10952674B2 (en) | 2015-05-13 | 2021-03-23 | University Of Florida Research Foundation, Incorporated | Wireless battery-free diagnostic mouth guard |
US11109808B2 (en) | 2015-10-23 | 2021-09-07 | University Of Florida Research Foundation, Inc. | Intelligent fitness and sports mouthguard |
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US10517525B2 (en) | 2013-01-14 | 2019-12-31 | University Of Florida Research Foundation, Inc. | Smart diagnostic mouth guard system |
US10952674B2 (en) | 2015-05-13 | 2021-03-23 | University Of Florida Research Foundation, Incorporated | Wireless battery-free diagnostic mouth guard |
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WO2017054396A1 (en) * | 2015-09-29 | 2017-04-06 | 京东方科技集团股份有限公司 | Intelligent tooth jewellery and usage method thereof |
US11109808B2 (en) | 2015-10-23 | 2021-09-07 | University Of Florida Research Foundation, Inc. | Intelligent fitness and sports mouthguard |
US10321875B2 (en) | 2016-04-06 | 2019-06-18 | At&T Intellectual Property I, L.P. | Determining food identities with intra-oral spectrometer devices |
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US11064945B2 (en) | 2016-04-06 | 2021-07-20 | At&T Intellectual Property I, L.P. | Determining food identities with intra-oral spectrometer devices |
US11504060B2 (en) | 2017-06-23 | 2022-11-22 | Martha Ann Keels | Dental retainer with pH sensor |
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Also Published As
Publication number | Publication date |
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WO2005115225A3 (en) | 2006-04-13 |
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