DE60116520T2 - MICROCHIP RESERVOIR DEVICES WITH WIRELESS TRANSMISSION OF ENERGY AND DATA - Google Patents

Abstract

A method is provided for monitoring the status of a medical device implanted in a patient. The method includes the steps of implanting in a patient a medical device which comprises (i) a substrate in which two or more reservoirs are located, with each covered by a reservoir cap, (ii) a drug or sensor located in the reservoir, (iii) a power source and actuation electronics for disintegrating or permeabilizing the reservoir cap, and (iv) a telemetry system; and then using said telemetry system to wirelessly transmit to a remote controller data about the condition of the power source and/or data about which reservoirs have been or have yet to be activated to release the drug therefrom or to expose the sensor therein.

Description

background the invention

The The invention relates to miniaturized devices for controlled exposure or releasing molecules, such as. Drugs and / or auxiliary devices such as Sensors.

Microchip devices for chemical and drug delivery and controlled exposure of container contents have been described in detail US 5,797,898 . US 6,123,861 , WO 01/64344 and WO 01/35928. One group of embodiments of these microchip devices provides for actively releasing or exposing the contents of a container in the substrate of the device. "Active" is used to refer to those embodiments in which the release is initiated at a certain time by the application of a stimulus to the device or a part of the device.

A important application of these active microchip devices is as implantable Device for feeding Medicines in the body to serve humans and animals for treatment or diagnosis of diseases. Because of its small size, the microchip device in the body be implanted in various places, including, but not limited on, such under the skin and in the abdominal cavity. The device can also for the Drug delivery or content exposure along the gastrointestinal tract be taken. The flexibility of the implantation site and Job variation is especially important, for example when local Application, instead of a systemic, is desired. Currently available implantable drug delivery devices, such as Pumps, can for use in many places in the body too be great.

US 5,797,898 (Santini et al.) Describes the power supply of active microchip devices by means of pre-charged energy sources (eg pre-charged microbatteries) that can be integrated into the microchip and its associated electronics. Such precharged microbattery may be a thin film battery created on the microchip substrate itself, or it may be a separate component connected to the microchip substrate via feedthroughs and packaging. Such power sources generally need to store all of the energy needed during the operating life of the microchip device. If it can not store all the energy needed during the intended useful life of the microchip device then the depleted battery has to be replaced with a new one. However, such replacement is typically impractical or undesirable for an implanted device. Additionally, conventional measures for powering an implantable device may be inappropriate for a variety of implantable devices, particularly for all possible implant sites.

US 5,797,898 also describes the integration of a preprogrammed microprocessor into the active microchip device to control which containers are activated and when. According to the disclosure, the microprocessor is fabricated on the back side of the microchip substrate. It would be advantageous to be able to change programming after implantation in order to make the microchip device more flexible and adaptable to different applications, especially implant applications.

It is therefore an object of the invention to provide devices and methods for the need after precharged power sources for microchip devices to active Release or exclude.

It is another object of the invention to provide devices and methods to the explantation of implanted microchip devices for the purpose of replacement or Recharging the power source of the device or for the purpose of reprogramming of the device microprocessor avoid.

It It is another object of the invention to provide additional means of energy supply and communication with drug delivery and sensor microchip devices disposal to deliver.

These and other objects, features and advantages of the invention will become apparent the following detailed description of the invention in conjunction with the drawings and the attached claims seen.

Demolition of invention

Devices, systems and methods become the wireless power supply and / or communication with microchip devices, the for controlled exposure and release of container contents, such as e.g. drugs Reagents and sensors, used, are provided.

In a preferred embodiment, the system for controlled exposure of container contents (1) comprises a microchip device having a substrate with a plurality of containers containing container contents to be exposed and / or (2) a rechargeable or on demand source of energy , which has a local component that can wirelessly receive power from a remote transmitter, wherein the received energy, directly or after conversion mung, for activating this exposure or releasing the container contents is usable. Advantageously, these systems do not require an energy storage unit physically connected to or integrated with the microchip device. For example, the local component may be configured to receive energy from an electromagnetic energy source, such as radio frequency signals or a laser, and / or from a sonic energy source, such as an ultrasound generator. The system may optionally include a rechargeable energy storage unit, such as a capacitor or rechargeable battery. However, it does not have to store all of the energy needed for the lifetime of the microchip because additional power can be wirelessly transmitted and received when needed (ie, on demand). The rechargeable energy storage unit may include, for example, a coil for receiving electromagnetic energy, a photocell, a hydrophone, or a combination thereof.

The System may also include drive electronics, local controls and a Include telemetry system. Drive electronics, such as Multiplexer / demultiplexer, controls selectively and passes the energy on to the containers selectively to open. The local controller can control the drive electronics and can Microprocessors, ROM, RAM, clocks, analog input / output devices, digital I / O devices, programmable logic devices and combinations thereof include. A telemetry system transmits wireless Data (e.g., a signal) between the microchip device and a Remote control.

In another preferred embodiment The system provides for the controlled release or exposure of container contents (1) a microchip device, having a substrate with a plurality of containers to be released or container contents to be exposed contains and (2) a telemetry system for wireless transmission of data between the microchip device and a remote control. The system may further drive electronics for selective opening the container and a local controller (typically in wireless communication link with the remote control of the telemetry system would be) to control the drive electronics.

System, such as. external / internal transmitters or remote controls that light or use variable wavelengths.

It It should be noted that wireless energy transmission and wireless Data transfer to the microchip device sent in the same signal and then suitable in the microchip device can be separated.

The Microchip device systems can used in a variety of applications. A preferred Application is the controlled delivery of a drug, chemical Reagent or biosensor at sites in the body of a human or animal. In one example, the microchip device is for implantation on or set up in the eye of a human or animal, and remote control and / or energy source has an ophthalmic laser. In In another example, the microchip device is suitable for oral administration, and the remote control has a radio frequency transmitter.

The System also has many Uses that are not limited to implantation. For example, the container contents a sensor for detecting a chemical or biological molecule at the location where the microchip device is placed, and the telemetry system sends a sensor detection status to the remote control. Such a site could be in vivo or in vitro be. The chemical or biological molecule could be e.g. on a chemical or biological weapon, and the system in an early warning / detection system be used.

In a preferred variant of the embodiments described above every container can have one container lid have on the container over the Container contents releasing or exposing the contents of the container by diffusion through the container lid or disintegration of the same is controlled. The container lid may be an anode, so when applying an electrical potential between a cathode and the anode of the container lid is oxidized to facilitate its disintegration, eliminating the container contents to the surrounding liquid is exposed.

Of the container capacity is preferably a drug, a biosensor or a combination from that.

Summary the figures

1 is a schematic of the basic components of a system for wirelessly transferring energy or data to or from a microchip device to release or expose container contents.

2 (a) illustrates an embodiment of a configuration of a laser-equipped microchip drug delivery system for energy and data transmission, and 2 B) a process of using an ophthalmic laser for energy and data transfer to a drug delivery implant in the eye.

3 Figure 10 is a diagram illustrating how a microchip device may be activated at a particular location in the gastrointestinal tract due to the location of a drug delivery microchip device relative to an rf transmitter.

incoming Description of the invention

Devices, systems and procedures were for wireless Energy supply and / or communication with microchip devices developed, the for the controlled exposure and release of container contents, such as e.g. drugs Reagents and sensors are used.

The microchip device systems

The Systems include a microchip device, along with a means for the wireless supply of power (power) to the microchip device, a means for wireless transmission data between the microchip device and a remote control, or both.

The microchip device

The Microchip device U.S. Patent Nos. 5,797,898 and 6,123,861 (Santini et al.), and WO 01/64344, WO 01/41736, WO 01/35928 and WO 01/12157, the whole hereby be incorporated into this description by reference. each Microchip device includes a substrate having a plurality of containers, the contain container contents to be released or exposed. In a preferred embodiment every container has one on the container over the container contents located container lid, releasing or exposing the contents of the container by diffusion the container lid or disintegration of the same is controlled. The container lid may be an anode, so when applying an electrical potential between a cathode and the anode of the container lid is oxidized to facilitate its disintegration, eliminating the container contents to the surrounding liquid is exposed.

In another embodiment includes the container lid an electro- or thermo-responsive polymer, its integrity or porosity Applying electrical energy to the container lid (e.g., the electro-responsive Polymer) or an adjacent resistor (e.g., the thermo-responsive one) Polymer) (i.e., increased or humiliated). Similar can the container lid include or consist of a polymer having a porosity which by application of electrical energy, acoustic energy or a certain chemical species (e.g., for chemical propulsion), the from the microchip device or delivered to another source, can be modulated.

The Microchip reservoir contents can Essentially any chemical or miniature device. In a preferred embodiment the chemical is a therapeutic, prophylactic or diagnostic Active ingredient. (The term "drug" is here for any Type of such drug used.) Preferred Drug Delivery Applications include highly effective compositions, including both small and big (i.e., macro) molecules, such as. Hormones, steroids, chemotherapy treatments, vaccinations, Gene delivery vectors and some strong analgesic agents. One Example of a diagnostic agent is an imaging agent such as. a contrast agent. Other molecules that are released can, include perfumes and flavors.

The container contents can also catalysts (e.g., zeolites, enzymes), one or more reagents, or a combination of them. In another embodiment includes the contents of the container an auxiliary device such as. a sensor or a sensor component, e.g. a biosensor. examples for Sensor components include components used in the measurement or Analysis of the presence, absence or modification of a chemical or ionic Species, electromagnetic or thermal energy (e.g., light) or one or more physical properties (e.g., pH, Pressure) can be used at one point. The contents can either from the container be released or remain immobilized therein, depending from the particular application. Individual containers can contain several types of chemicals, several types of devices or combinations of devices and contain chemicals.

The microchip devices can be produced and constructed by means of microfabrication methods known from the prior art, in particular those in US 5,797,898 and US 6,123,861 (Santini et al.), And WO 01/64344, WO 01/41736, WO 01/35928 and WO 01/12157.

Wireless power supplies / energy sources Desire

medium for powering active-release microchip devices the use of a pre-charged energy source (the whole for operation over the Lifetime of the microchip device needed Contains energy), a source that can be recharged periodically, and one on demand working energy source. The two latter sources of energy are favored.

The Microchip device typically includes a converter to receive wirelessly the device transmitted energy, circuits for supplying or converting the received energy into a usable or storable form and, if storable, a storage device, such as a rechargeable Battery or capacitor. That's why the system involves being controlled Releasing or exposing container contents in preferred embodiments a microchip device and a rechargeable or on demand source of energy. The on demand working energy source demands more favorably Do not imply that an energy storage unit is physically connected to the microchip device or integrated into it. The rechargeable energy source (i.e. the rechargeable energy storage unit) can store energy, but advantageously does not need the whole for the service life of the microchip needed Save energy. The rechargeable source of energy and on demand working energy sources can both in a single microchip device be included as it is for a system common is that an on-demand power source is an energy storage unit, such as. includes a capacitor or a battery.

The Systems described herein are preferably provided with a means for monitoring the state of any energy storage unit equipped. While Energy consumed or emptied from the energy storage device can be extra If necessary, power to the rechargeable energy storage unit wirelessly be sent and received by this. Rechargeable energy sources provide a means to increase the operating life of the microchip device over those In addition, those with pre-charged memory cells or non-rechargeable Systems possible is to extend.

Wireless transmission systems and methods that may be adapted for use with the microchip devices described herein are, for example, US 6,047,214 (Mueller et al.), US 5,841,122 (Kirchhoff), US 5,807,397 (Barreras) and US 5,324,316 disclosed. The systems typically involve a receiver and a transmitter of one or more types of energy. The rechargeable or on-demand power source preferably includes a local component that can wirelessly receive power from a remote transmitter. In this disclosure, the term "local" refers to being local to the microchip device (rather than remotely) and includes, but is not limited to, the local component being attached to the microchip device, such as by fabrication on the substrate.

The Local component can receive energy via a variety of means be furnished. For example, the local component can do this be set up, energy from an electromagnetic (EM) energy source, or an acoustic (i.e., sonic) energy or other mechanical To receive energy source. Electromagnetic energy refers on the entire spectral range from X-ray to infrared. Representative examples useful EM energy types include radio frequency signals and Laser light. One representative An example of a useful type of acoustic energy is ultrasound. In various embodiments For example, the rechargeable energy storage unit may be e.g. a coil for receiving electromagnetic energy or a means for forming other types of energy, such as a photocell, a hydrophone or a combination of these. Additional components can be added Energy conversion means, e.g. a rectifier, a Energy storage unit, such as a battery or a capacitor, and control of electrical potential / current (i.e., potentiostat / galvanostat) include.

The microchip device may also include a component for converting mechanical or chemical energy from the human or animal body into energy / power that may be utilized to activate the release or exposure of the container contents. For example, accelerometer and gyroscope components can be used to convert body movements into electrical energy. Similarly, an implanted transducer can convert heartbeats into usable energy, as is currently done in some pacemaker designs. See eg US 5,713,954 , In another embodiment, energy is generated / converted from a chemical energy source. For example, the microchip device may include a biofuel cell that generates the energy from the chemical reaction of a molecule present in the body. Examples of these fuel cells are in Palmore u. Whitesides, "Microbial and Enzymatic Biofuel Cells", Enzymatic Conversion of Biomass for Fuel Production, Enzymatic Conversion of Biomass for Fuel Production, ACS Symposium Series 566: 271-90 (1994), Kano et al. Ikeda, "Fundamentals and Practices of Mediated Bioelectrocatalysis", Analytical Sci., 16 (10): 1013-21 (2000) and Wilkenson, Autonomous Robots 9 (2): 99-111 (2000 ). In a typical embodiment, the implanted device would have an immobilized enzyme that reacted with a biological molecule to induce electron transfer and thus the flow of an electrical current. Possible useful biological molecules include triphosphates, such as ATP, and hydrocarbons, such as sugars like glucose.

Lots of these components (except the external energy transfer source) can on the microchip ("on-chip" components) by means of known MEMS production techniques, e.g. in Madou, Fundamental of Microfabrication (CRC Press 1997), or by known microelectronic process techniques, the e.g. in Wolf u. Tauber, Silicon Processing for the VLSI Era (VLSI-era silicon processing) (Lattice Press 1986) are. Each of these components (except the external energy transfer source) Also available as a discrete, off-the-shelf microelectronic Components exist with the microchip devices using hybrid electronic components or multi-chip modules (MCM) are connected. An active-release microchip device with the Ability, Energy over Receiving wireless media may also be a combination of on-chip and off-the-shelf components consist.

Of the The specific energy requirement of the microchip device depends on the application and specific Design of the microchip device from. examples for Design factors include size requirements and expected Operating life of the device. The special devices and methods of energy transfer hang probably from the for the microchip device and the remote transmitter selected Places off. For example, affects an implanted microchip the body tissue the energy transfer from an outside located transmitter. For example, inductive coupled penetrates electromagnetic energy the body tissues typically to a limited extent; however, sound energy, e.g. Ultrasound, easily transmitted through tissues and body fluids. As another example, although (visible) light is generally not transmitted through tissue It can easily be due to the humor aquosus and humor vitreus des To be transmitted to the eye. However, other electromagnetic radiation, e.g. X-rays, easily transmitted through tissue become dependent primarily on the wavelength the radiation.

In In one form, the system provides remote charging of a battery for power a microchip device ready.

In an embodiment with an in vivo rechargeable energy storage unit is the Energy storage unit from the other electrical in vivo components disconnects and communicates with them via wire or in vivo telemetry. See, e.g. the implantable ones described in PCT WO 01/37926 and WO 01/28629 Cardiac apparatus and energy transmission systems.

The System may further include a telemetry system to wirelessly Data (e.g., a signal) between the microchip device and a Remote control or to transfer between components of the microchip device.

Wireless communication media / telemetry systems

medium for sending and receiving data using wireless technology the for the wireless energy transfer described similarly. In a preferred embodiment includes the system for controlled release or exposure of container contents a microchip device and a telemetry system for the wireless data transfer between the microchip device and a remote control. In general, the telemetry system includes a transmitter and a receiver. A transmitter can be in the remote control, the microchip device or both be included when transmitting data in both directions (to / from the microchip device) be when the receiver in the microchip device, contained in the remote control or in both. In this revelation can the "remote control" therefore a transmitter, receiver or both.

In general, telemetry (ie, transmission and reception) is achieved by means of a first coil for inductively coupling electromagnetic energy to a matching / corresponding second coil. Means for this are well known, with different modulation schemes such as amplitude or frequency modulation to transmit the data on a carrier frequency. The choice of carrier frequency and modulation scheme depends on the location of the device and the bandwidth required, among other factors. Other data telemetry means are also usable. Examples include optical communication, wherein the receiver is designed as a photocell, photodiode and / or phototransistor, and the transmitter as an LED or laser. For example, an LED could be fabricated on the silicon microchip substrate, either inside or outside the container, using or adapting methods such as those described in Barillo, et al., "A porous silicon LED based on a standard BCD technology". "A Porous Silicon LED Based on Standard BCD Technique"), Optical Materials 17 (1-2): 91-94 (2001), optical telemetry methods are further described in, for example, US Pat US 6,243,608 described. For soft tissue telemetry of the body, acoustic (ie, sonic) energy, such as ultrasound energy, may be used as the means of communication. See eg US 6,140,740 , One skilled in the art can adapt these known telemetry means for use with a microchip device to optimize energy and data exchange. For example, you can use an Impedan Adaptation to tissue and reception field and other factors to optimize ultrasound transmission.

In various embodiments is the microchip device with a receiver equipped, the Commands and data from the remote control and can be used become a container too actuate, State information about to request the status of the system or an event log or that Re-program the control operating system (i.e., the internal firmware). In one embodiment, at the microchip device implanted in a human or animal can be the remote control a means for displaying and / or driving, by the doctor or patients for Operation or monitoring of the microchip device is usable. For example, the microchip device may be connected to a a receiver having, remote control information about the battery condition and wirelessly transmit the location and number of used and remaining containers. additional Auxiliary circuits can be used for interfaces to biosensors or other device types such as. Pacemakers or defibrillators are used.

Other components and Characteristics of the systems

It It should be noted that wireless energy transmission and wireless Data transfer to the Microchip device transmitted in the same signal and then can be separated in a suitable manner in the microchip device.

The here described systems further include drive electronics and local controls. drive electronics controls selectively and supplies energy to the desired containers. The drive electronics contains Circuits to bring the energy into a shape that opens to the Container is needed. For example, you can these circuits include signal generators / oscillators, voltage or power sources, amplifiers and / or switches. For metal film container lids includes the Drive electronics preferably a potentiostat. Representative Types of drive electronics include potentiostats / voltage sources, Galvanostats / current sources, multiplexers and demultiplexers. In a preferred embodiment the drive electronics preferably include a demultiplexer, to direct the power supply to the desired containers. The demultiplexer can be integrated on the microchip or a separate chip or be electrical component.

The local controller can control the drive electronics and is typically responsible for the operation of the device. The complexity of the control depends on the particular application on the microchip. The controller is generally either a microprocessor-based system or a dedicated logic device with a finite number of operating states. In the case of the microprocessor based system, there is preferably a microprocessor, memory (ROM and RAM), clock, analog input / output devices and digital input / output devices. The memory generally includes a set of instructions for execution by the microprocessor. These commands may include routines for driving the containers, receiving commands or data from the remote control, sending information to the remote control, and measuring and interpreting signals from devices such as sensors. A control based on a dedicated logic device can be controlled by receiving commands or data in the form of a coded (voltage) signal. See eg US 5,324,316 which describes the use of a dedicated logic device as the controller of an implantable microstimulator. The components of the control system may be integrated as part of the microchip on the same substrate or be separate local components.

use the microchip devices and systems

The Microchip device systems are useful in a wide variety of applications. The applications can ex vivo or in vitro, but more preferred are in vivo Applications, especially as a result of non-invasive or minimally invasive implantation.

preferred Applications for the use of the devices and systems involve the controlled delivery of a drug (i.e. a therapeutic, prophylactic or diagnostic agent) in places in the body of a human or animal, biosensory feeling or a combination from that. The microchip systems are particularly useful in drug therapies useful in which the control of the exact amount, rate and / or Time of drug delivery desired is. Preferred drug delivery applications involve delivery highly effective compositions, including both small and large molecules, e.g. Hormones, Steroids, Chemotherapy Treatments, Vaccinations, Gene Delivery Vectors and some strong analgesic agents.

The microchips can be implanted with a surgical procedure or injection, or swallowed, and can deliver many different medications, with varying rates and varying times. In one example, the microchip device is adapted for implantation on or into the eye of a human or animal, and the remote control includes an ophthalmic laser. In another example, the microchip device is set up for oral administration and the remote Control includes a radio frequency transmitter.

In another preferred embodiment includes the microchip device one or more biosensors (which may be sealed in containers until she for the use needed) for detecting and / or measuring of signals in the body of the patient are. In this disclosure, the term "biosensor" includes sensor devices, the chemical potential of an analyte of interest in one transform electric signal, as well as electrodes, the electrical Signals directly or indirectly (e.g., by converting mechanical or measuring thermal energy in an electrical signal) without looking at it limited to be. For example, the biosensor may be intrinsic electrical Signals (ECG, EEG or other neural signals), pressure, temperature, pH or stress of tissue structures at various in vivo Measuring places. The electrical signal of the biosensor can then be measured be, e.g. from a microprocessor / controller, then the information to a remote control, another local controller, or both can. For example, the system can be used to provide information about the Life functions of the patient or the implant environment, such as e.g. Blood gases, drug concentration or temperature, pass or record.

The System also has a variety of uses that are not based on implantation are limited. For example, you can the container contents a sensor for detecting a chemical or biological molecule at the Place where the microchip is located, and transmit the telemetry system a state of sensor detection to the remote control. Such Site may be in vivo or in vitro. The chemical or biological molecule can e.g. related to a chemical or biological weapon, and the system will be in an early warning / detection system used.

active Microchip devices can controlled by local microprocessors or via remote control become. Biosensor information can be used by the control input to determine the time and mode of activation by automatic means, by human Intervene or provide a combination thereof. The microchip devices have numerous in vivo, in vitro and commercial diagnostic applications. The microchips are capable of delivering precisely measured quantities of molecules, and are so for useful in vitro applications, such as analytical chemistry and medical diagnostics, as well as biological applications like the supply of factors to cell cultures.

The Invention may best be understood by reference to the following non-limiting Examples are understood.

Example 1: Microchip for chemical release with electrochemical drive and RF energy transfer

An electrochemically actuated microchip with containers covered by gold-thin-film container lids can be made with the in US 6,123,861 be prepared described methods. The containers contain drug or other release molecules. Applying an electrical potential of about 1.0 V (with respect to a saturated calomel reference electrode) in the presence of chloride ions would cause the container lids to oxidize and disintegrate and release the material stored in the container. An on-demand power control system would include a rf generating and a transmission source into an external control unit. The microchip device would include a receiver coil (ie an inductor), an optional energy converter (rectifier, regulator), an energy storage unit (eg a capacitor, microbattery), optional potentiostat or galvanostat circuit (if modulation of electrical potentials or currents is needed), a demultiplexer, a timer and a microprocessor include.

If releasing from a particular container is desired, becomes an RF signal (wireless) to the container containing microchip device Posted. The RF signal would induce an alternating electrical current in the receiver coil. This rf-generated alternating current can be rectified to dc and led to a unit for energy storage, or, if the behavior of the container lid is well characterized in terms of electrical current / corrosion, then the power can go directly to the anode tank lid which covers the particular container from the release required is. In some cases the energy received is through a galvanostat or potentiostat directed to modulate the current or a specific electrical Potential (relative to a reference electrode) on the container lid to create. The electric current or the voltage is applied to the correct container passed through a microprocessor-controlled demultiplexer. Of the Microprocessor can with memory (memory) and be coupled to a timer to schedule on-chip dose schedules to save.

The microprocessor may then route energy from the energy storage unit or directly from the rectifier to the correct container in a particular release pattern programmed in memory. The sharing pattern could also be on be controlled wirelessly by commands sent by a remote control via a telemetry system. Alternatively, the release of the drug or other molecules could be controlled by feedback from a biosensor located on or near the microchip device and having an interface to the controller.

This example may be better in reference to 1 which is a scheme representing the major components and energy and data flow in a wireless microchip system.

Example 2: Microchip for selectively exposing container contents to thermal Activation and RF energy transfer

One Microchip device, similar to that described in Example 1, may be formed with containers, the catalysts for Reactions and / or sensors for the detection of chemical and biological agents containing wireless energy transmitted to open the Container, to selectively expose the contents can be used. In this embodiment Electromagnetic energy is sent to a receiver coil, which itself on the microchip device is or is connected to it. The induced alternating current can rectified to DC, to a storage battery or to charge a capacitor, or sent directly to resistors which are located on, near or in the containers to be opened. Flowing through the resistance Power causes a temperature increase in the resistance and surrounding area. The increase in temperature may disintegrate the container lid material, melt or change phase and selectively select the sensor or catalyst expose. Alternatively, a temperature rise in the container can Pressure increase in the tank revealed that the container lid tear leaves, what the contents of the container exposed to the environment. As in Example 1, the supply of the Power to the true tank by using one of a pre-programmed microprocessor, a remote control or a biosensor controlled demultiplexer achieved.

Example 3: Microchip to release a drug into the eye by laser drive

laser are routinely included Eye surgery and other eye procedures for the treatment of states such as diabetic retinopathy, retinal detachment and age-related macular degeneration used. Some states, especially macular degeneration, are through regular drug administration treatable to the eye; currently available Means for such as. Injections, however, are difficult. To these difficulties to overcome, For example, an implantable microchip device may be provided to receive a extended period of time cans of one or more types of medication on a regular basis to the eye. As the energy demand in electrochemically actuated silicon microchip devices with Gold thin film container lids sufficiently small, the energy can be delivered wirelessly, for example about an ophthalmic laser. The ophthalmic laser can also do this can be used to communicate commands wirelessly to the implanted microchip device. Both energy and data can to be sent, e.g. by modulating the energy carrying one signal; to communicate the modulation information [to] to the implanted microchip device.

Such an implantable wireless eye delivery system would typically include (1) the drug-retaining microchip with its local control, external interfaces, power conversion electronics and drive electronics, and (2) the ophthalmic laser. The external interface and power conversion electronics would typically include a photocell for receiving incident light energy, circuitry for generating the required voltage, storage means such as a capacitor or a battery, and circuitry for decoding information transmitted by modulating the laser input. The controller would typically be a microprocessor with associated auxiliary circuitry, such as a memory memory and a clock, although a dedicated IC may operate in certain embodiments. Electronics needed to drive electrochemical microchips would typically include means for controlling the electrode potential, such as a potentiostat or galvanostat, and a demultiplexer for supplying the potential to the desired container. If desired, the system would provide feedback, for example to confirm the successful delivery of a dose. This information may be sent back to the operator or a computer monitoring system, either optically by means of an LED or in other ways of wireless transmission such as RF. 2A represents a possible design of the microchip device configuration, wherein the microchip device 10 a series of containers containing drug to be released 12 , Energy conversion, drive electronics and local control area 14 , Photocell 16 , LED or wireless telemetry transmitter 18 includes.

An ophthalmologist could initiate release of the drug and initiate communication with eye-implanted microchips by directing an ophthalmic laser onto the appropriate area of the microchip in the patient's eye. Please refer 2 B . the one eye 20 with optical nerve 21 represents, wherein the microchip device 28 implanted on the inside of the eye at the back. An ophthalmic laser 30 conducts energy and data via laser light 32 through the cornea 22 , Lens 24 and humor vitreus 26 , for power supply and communication with the implanted microchip device 28 , Many ophthalmologists are already experienced in using such lasers, so this procedure is easy to perform.

Example 4 Orally administered Microchips for drug delivery with proximity actuation

One potential Advantage of orally administered drug delivery microchips or sensors is that they are at specific time or at specific sites in the gastrointestinal tract can be activated. Such control of time and place of release is using pre-programmed microprocessors, remote control systems (e.g., wireless systems) or biosensors. A procedure, to drug release or exposure of a sensor to a initiate a special site in the gastrointestinal tract, the Using a wireless remote control system that is high location-dependent is. For example, could a patient who is swallowing an orally administered microchip has a small RF transmitter on his belt wear. The field generated by the RF transmitter would be designed to absorb the energy to localize to a specific site in the gastrointestinal tract. Multiple coils or antennas could be used to make the field more accurate locally set up so that its signal detectable only at the desired location is. The microchip would through the gastrointestinal tract (GI tract) to hike to a place reaches where it detects the signal from the transmitter.

As in example 1 would The microchip received energy from the RF transmitter and could be drug release or expose internal sensors. The position of release or exposure in the gastrointestinal tract would be due to the nature of the RF transmitter incoming signal (i.e., signal strength) Arrangement of the transmitter (e.g., its position on the patient's belt) and the Distance between microchip and transmitter (which depends on how far the microchip has migrated in the gastrointestinal tract).

This process is in 3 shown a microchip device 50A at a first location (namely the mouth) in the GI tract, the microchip device 50B in a second place (namely, the large intestine) and the RF transmitter 54 with a rf signal range according to the dashed line 56 represents. When passing through the GI tract, the device moves from place 50A that are outside the rf signal range 56 lies, to the spot 50B that are in the rf signal range 56 lies and from the signal of the rf-transmitter 54 can be supplied with energy.

Example 5: To minimize medical error designed microchips

The Including a microprocessor, memory and timer can also help the opportunity a drug overdose or Administration of wrong medication to patients. security protocols can stored in the memory and constantly checked by the microprocessor, um (i) releasing too much drug to a patient via certain time interval and / or (ii) the simultaneous release of two or more incompatible Prevent medication. additionally can the microchip in memory storage the exact amount of the supplied Store medication, its delivery time and the amount of microchip remaining drug. This information can be obtained using wireless technology (for implants) or using standard computer connections (for external, inline or intravenous systems) to the doctor or a central monitoring system be transmitted on a real-time basis. This allows the physician remote monitoring the condition of the patient.

amendments and variants of the methods and apparatus described herein one skilled in the art from the foregoing detailed description. Such modifications and variations are intended as falling within the scope of the appended claims.

Claims (35)

System for controlled exposure or release container contents, With - one Microchip device comprising a substrate having a plurality of containers, contain the container contents to be exposed or released; and - one rechargeable or on demand working energy source, the one local component that has wireless power from a remote Can receive broadcasters, being the energy received, directly or after transmission, to enable exposure or release of container contents is usable. The system of claim 1, wherein the remote Transmitter transmits electromagnetic energy or mechanical energy. The system of claim 2, wherein the electromagnetic Energy from the radio frequency signals, microwave signals, infrared light, visible Light and ultraviolet light group is selected. A system according to claim 2 or 3, wherein the mechanical Energy contains acoustic energy. A system according to any one of claims 1 to 4, wherein the Power source has a rechargeable energy storage unit. The system of claim 5, wherein the chargeable Energy storage unit a capacity or a rechargeable battery having. A system according to claim 5 or 6, wherein the chargeable Energy storage unit further comprises a coil for receiving electromagnetic Energy, a photocell, a hydrophone or a combination thereof having. A system according to any one of claims 1 to 7, wherein the Power source has an on demand working power supply. A system according to any one of claims 1 to 7, wherein the Both a source of energy supply on demand and a rechargeable energy storage unit. A system according to any one of claims 1 to 9, further comprising Drive electronics for the selective control and forwarding of Energy for selective opening the container. The system of any one of claims 1 to 10, further comprising Telemetry system for wireless data transmission between the microchip device and a remote control. The system of any one of claims 1 to 9, further comprising - one Drive electronics for the selective control and forwarding of Energy to selectively open the Container, - one local control for controlling the drive electronics, and - one Telemetry system for wireless data transmission between the microchip device and a remote control. System for controlled exposure or release container contents, With - one Microchip device comprising a substrate having a plurality of containers, contain the container contents to be exposed or released; and - one Telemetry system for wireless data transmission between the microchip device and a remote control. The system of claim 13, further comprising drive electronics for selective opening the container. A system according to claim 10, 12 or 14, wherein the drive electronics components from the multiplexer, demultiplexer, Signal generators, signal oscillators, amplifiers, switches, potentiostats and Combinations thereof comprising group. The system of claim 10, 12, 14 or 15, further with a local control for controlling the drive electronics. The system of claim 17, wherein the local Control components from the microprocessors, ROM memory, RAM memory, Timers, analog input / output devices, digital input / output devices, programmable Logic blocks and combinations thereof comprising group. A system according to claim 16 or 17, wherein the Local control wirelessly with the remote control of the telemetry system Can exchange information. A system according to any one of claims 11 to 18, wherein the data transmission achieved by means of a first coil in the microchip device, inductively electromagnetic energy to a corresponding Coupling coil in the remote control. A system according to any one of claims 11 to 19, wherein the remote control an LED, a laser or an ultrasonic transmitter having. A system according to any one of claims 11 to 20, wherein the microchip device comprises a receiver with a component comprising photocells, photodiodes, phototransistors and ultrasound receivers Group has. A system according to any one of claims 1 to 21, wherein the Tank content a drug, a sensor or a combination thereof. A system according to any one of claims 1 to 22, wherein each container one on the container above the Container capacity arranged container lid has, and in which exposing or releasing the container contents by diffusion through the container lid or whose decay is controllable. The system of claim 23, wherein the microchip device further comprising a cathode, at least one container lid is an anode and an electric potential between the cathode and the anode for Oxidizing the container lid and exposing the container contents can be applied to an ambient fluid. System according to one of claims 1 to 24, in which the microchip device is suitable for implantation on or into a human or animal eye, wherein the container contents comprise a medicament and / or a sensor and the remote control contains an eye laser. A system according to any one of claims 1 to 25, wherein the Microchip device is suitable for administration in vivo, wherein the container content Drug and / or have a sensor and the remote control contains a radio frequency transmitter. A system according to any one of claims 11 to 26, wherein the container contents contain a sensor for detecting a chemical or biological molecule, wherein the telemetry system has a status of this detection of the Sensor transmits to the remote control. The system of claim 27, wherein the chemical or biological molecule refers to a chemical or biological weapon. The system of claim 28, wherein the container contents also an antidote for have the chemical or biological molecule. The system of any one of claims 11 to 29, further comprising rechargeable or on demand working energy source, the one local component that has wireless power from a remote Sender can receive. A microchip device for controlled exposure or release container contents in one Human or animal, with - one Substrate having a plurality of containers to be exposed or container contents to be released contain; and - one Component that releases mechanical or chemical energy from the body of the body Turns humans or animals into energy that activates the exposure or releasing the container contents is. A microchip device according to claim 31, wherein the component one upon movement of the body or part of the body transferred mechanical force into energy. A microchip device according to claim 31 or 32, wherein in which the component comprises a biofuel cell containing the Energy generated by the chemical reaction of a molecule present in the body. Method of controlled exposure or release of container contents a microchip device in one place, with the following steps: - Procure the system according to one of the claims 1 to 30, wherein the microchip device at a first location in vitro and the remote transmitter or remote control a second location distal to the first location; and - wireless transmission of energy from the remote transmitter or remote control the microchip device in one to activate the exposure or releasing the container contents sufficient amount. The method of claim 34, wherein the container contents a therapeutic, prophylactic or diagnostic agent exhibit.