JP2013539669A - Microdevices for biomedical applications and uses thereof - Google Patents

Abstract

The present invention provides microdevices for biological applications and methods of using the same, each microdevice including an outer membrane and properties, and having a size of about 1 angstrom to 5 millimeters.
[Selection] Figure 3

Description

  While significant progress has been made in the area of medicine and biology, especially genomics, over the past 10-20 years, traditional approaches to modern medicine, including prevention and treatment of diseases such as cancer, have remained essentially unchanged. Still, the focus is still mainly on macroscopic methods. For example, current disease diagnostic techniques use macroscopic data and information such as body temperature, blood pressure, scanned images, and measurement levels of chemical components in the body. Even the effectiveness of newly emerging DNA tests for the diagnosis of various diseases that are real-time, reliable, accurate, fast and cost-effective has not been established. Many diseases with high morbidity and mortality, including cancer and heart disease, are extremely difficult to diagnose early and accurately. In addition, most existing diagnostic techniques are invasive.

  The situation is worse when it comes to disease treatment. To date, many operations are still invasive, expensive, risk of complications, and require long recovery times. Some treatments even destroy healthy cells or tissues. One example is cancer treatment using radiation, which destroys not only cancer cells but also normal and healthy cells. Another example is blood related disease treatment, which is invasive and risky (eg open heart surgery), very expensive, and in many cases post-operative patients cannot return to normal active life .

  From the standpoint of preventing this problem, the causes of many diseases such as cancer are not yet known, other than the general guidelines for a healthy diet and regular exercise. This lack of knowledge about the disease directly leads to a lack of development of preventive drugs.

  Most of the above problems of prevention, diagnosis and treatment of modern medicine are, for example, lack of understanding of pathology at the microscopic level (cell biology level), effective drug delivery and efficient reaction mechanisms The lack of non-invasive and effective disease-targeted treatment methods and techniques, and lack of microscopic levels and preventive mechanisms and non-invasive monitoring with preventive approaches Many.

  In recent years, efforts have been put into the area of using nanotechnology for biological applications, mostly in vitro use. This in vitro effort has led to a slight development in the field. Pantel et al. Examined the use of microelectromechanical (MEMS) sensors to detect blood and bone marrow cancer cells in vitro (Non-Patent Document 1). Wozniak and Chen used laser tweezers and a micro needle to measure the force generated in the sample cells (Non-Patent Document 2). Kubena et al. Describes the development of MEMS for detecting biological agents in US Pat. No. 6,057,059, and Weissman et al. Describe the use of MEMS sensors for detecting biomaterial deposits in US Pat. Yes.

  Because of the above constraints, at the basic level, non-invasive treatment that minimizes microscopic detection, cancer prevention, early detection and normal tissue and organ damage in targeted treatment in vivo. Many of the problems faced by modern medicine, including those that remain unresolved. To date, however, most publications are limited to exceptions for in vitro detection, using systems that are relatively simple in construction and large systems that often have limited functionality. Highly integrated multifunctional microdevices (below 5 millimeters) have not been reported for advanced biomedical applications, particularly in vivo and at the microscopic level.

US Pat. No. 6,922,118 US6330885

Klaus Pantel et al., Nature Reviews, August 2008, 329 M.M. A. Wozniak et al., Nature Reviews, October 2009, 34

  In general, the present invention relates to a novel microdevice and its use for performing disease prevention, diagnosis or treatment at the microscopic level, and various novel functions achieved by integrating functionality at the microscopic level. And use micro device manufacturing technology of the state of the art such as integrated circuit manufacturing technology. Other manufacturing technologies include mechanical, chemical, chemical mechanical, electrochemical mechanical, electronic biochemical mechanical, biochemical, biochemical mechanical, optical, optoelectrical, optoelectromechanical, thermochemical The present invention may suitably include, but is not limited to, mechanical, thermomechanical, thermochemical mechanical circuits and integrated circuits, and semiconductor manufacturing techniques and production methods.

  In one type of application, the microdevice includes a plurality of components, each component typically ranging from a biological subcell unit size to a typical biological complete cell size (ie, 1 micron to several microns). 100 micron). Multiple components of various functions can be integrated into a single microdevice to perform various functions, such as disease detection, disease treatment and washing, usually at a microscopic level.

  Depending on the intended application, the microdevice of the present invention or the microdevice used in the present invention can be sized from 1 angstrom to 5 millimeters. Microdevice functionality includes sensing, detecting, measuring, diagnosing, monitoring, analyzing, drug delivery, selective absorption, selective adsorption, preventive procedures and performing surgical interventions or combinations thereof.

  In one aspect, the present invention provides a microdevice for use in medical applications or living biological systems.

In some embodiments, each device comprises an outer membrane, micromechanical properties, microchemical properties, microchemical mechanical properties, micro optical properties, microacoustic properties, microbiological properties, microbiochemical properties, microbiochemical machinery A microdevice comprising: a property selected from the group consisting of a property, a microelectronic biochemical mechanical property, a microelectrochemical mechanical property, a microelectromechanical property, a microelectromechanical property, a microacoustic mechanical property, and a microsuperconducting mechanical property. The size is about 1 angstrom to about 5 millimeters. For example, a microdevice with micromechanical properties can also be referred to as a mechanical device, which generally means that the mechanical properties perform the intended function of the microdevice.
In some examples of these embodiments, the microdevice is a micromechanical property, a microchemical property, a microchemical property, a micro-optical property, a microacoustic property, a microbiological property, a microelectromechanical property, a microelectromechanical property. , Including two properties selected from the group consisting of microacoustic mechanical properties and micro superconducting mechanical properties. In some other examples, the microdevice may further include a property selected from the group consisting of an attractive force related to a charged surface, chemical potential, geometric integrity, electromagnetic, and electrochemical potential. Depending on one or more other properties, the microdevice may be adsorbed to the surface of the target biological organ or cell structure.

  In some embodiments, the microdevice may be able to differentiate between normal cells and cancer cells. For example, by measuring the microscopic characteristics of cells including but not limited to biochemical properties, physical properties, electrical properties, electromagnetic properties, biochemical properties, mechanical properties, acoustic properties, thermal properties, optical properties, This function may be performed.

  In some embodiments, the microdevice measures microscopic characteristics of the organ structure and cell structure (eg, to have a detection probe), diagnoses the organ and cell structure at the microscopic level, ( Deliver the desired chemicals to the organ structure and cell structure at the microscopic level (for example, to have a microinjector or microcontainer with delivery capabilities) and the desired drug into the organ structure and cell structure at the microscopic level It may be possible to deliver and manipulate selected organ and cell structures at the microscopic level. The microdevice may perform the intended function in a non-invasive manner or in real time.

  In some embodiments, the microdevice has a surface charge, static potential, electrochemical potential, potential, surface wettability, contact angle, adhesion rate, temperature, density, friction force, hardness, surface tension, trace chemical concentration. It may be possible to measure at least one property selected from the group consisting of: hydrophobicity, hydrophilicity, pH, liquid flow rate, pressure, optical properties, absorption, adsorption and composition.

  The microdevice of the present invention may include a GPS, a signal transmitter, a signal receiver, a micromotor, a micropropeller, or a radio frequency (RF) communication chip. For this reason, the microdevice may be capable of local positioning, position identification, position information communication, and position adjustment.

  In some other embodiments, the microdevice is a chemical delivery function, a controlled chemical delivery function, mechanical action, controlled mechanical action, selective absorption, selective adsorption, detection at the microscopic level, electromechanical timed action Control electro-mechanical operation, control electro-chemical mechanical operation, control electro-biological operation, control electro-chemical biological operation, control electro-chemical biological operation, control electro-chemical bio-mechanical operation, by detected signal It may further include a function selected from the group consisting of operations initiated, operations initiated by external instructions. Such a function may be a result of the properties possessed by the microdevice or a particular subunit of the microdevice.

  In some other embodiments, the microdevice is pre-programmed for operation selected from the group consisting of chemical delivery to organic structures, mechanical force operation, charge injection, light emission, voltage application, cooling and heating. It may have a function. Such a function may be initiated by programming an on-chip device having memory and logic functions, e.g., an operation or series of operations is initiated when a sensing signal or response reaches a predetermined value, Executed. In some cases, the initiating function is the charge detected by the device, resting potential, potential, electrochemical potential, surface current, bulk current, surface wettability, adhesion, hydrophobicity, hydrophilicity, fluidity, electric field, magnetic field May be achieved by using from a group of parameters selected from the group consisting of: sound field, temperature, light wavelength and / or light intensity, friction force and coefficient of friction, hardness, pressure and external signal.

  In some embodiments, the microdevice has a dissolution capacity in the intended pH range (eg, 6-8 or 6.8-7.4) for 30 seconds to 3 days. That means that the microdevice may dissolve in that pH region during that period.

  In some embodiments, the microdevice comprises a material selected from the group consisting of polymers, organic materials, and inorganic materials that are relatively compatible with organic tissue. The expression “relatively compatible” means that the material is generally biologically compatible with the mammalian body and does not cause infection, disability, discomfort and other adverse effects (such as immunogenic effects). The microdevice can be manufactured using a biomaterial or using a biomaterial in combination with another material, or can be connected to or coated with a biomaterial. Biomaterials can include naturally occurring materials, synthetic materials or composite materials of naturally occurring materials (including autografts, xenografts or xenografts) and synthetic materials. Examples of such materials are silicon, silicon dioxide, polysilicon, silicon nitride, silicon oxynitride, carbon oxide and carbon nitride, polymers used for IC device packaging (predicted to be compatible due to inertness) , Lipids, peptides, hydroxyapatite (HA), calcium phosphate, calcium carbonate, magnesium phosphate, ammonium phosphate, silicates and nautilus shells.

  In some embodiments, the microdevice is from about 1 angstrom to about 100 millimeters (eg, for cell structure, DNA or bacteria related applications, for testing and analysis of human cells), from about 1 angstrom to about 100 microns ( For example, for selective deposition applications), it can be sized from about 0.01 microns to about 5 millimeters, from about 10 microns to about 2 millimeters, or from about 100 microns to about 1.5 millimeters.

  In some embodiments, the microdevice includes one material in which a plurality of subdevices are integrated in one unit with one or more functionalities. Examples of suitable materials include, but are not limited to, organic polymers, organic materials, biological materials, biochemical materials, inorganic conductors, inorganic semiconductors, inorganic insulators, and ceramics. Examples of suitable biological materials include, but are not limited to, artificial biological materials, natural biological materials, cultured biological materials, and combinations of natural biological materials and artificial biological materials.

  In some embodiments, the microdevice is from the group consisting of sensing functions, detection functions, measurement functions, calculation functions, analysis functions, diagnostic functions, logical processing (decision making) functions, transmission functions and surgical functions or surgical functions. An integrated microdevice that includes at least one selected function.

In some other embodiments, the microdevice is a voltage comparator, 4-point probe, calculator, logic circuit, memory unit, microcutter, microhammer, microshield, microdie, micropin, microknife, microneedle, Micro thread holder, micro tweezers, micro light absorber, micro mirror, micro wheeler, micro filter, micro chopper, micro shredder, micro pump, micro absorber, micro signal detector, micro drill, micro sucker, micro tester, micro container , Micro puller, signal transmitter, signal generator, friction force sensor, charge sensor, temperature sensor, hardness detector, sonic generator, light wave generator, heat generator, micro refrigerator and charge generator Further comprising a hardware that is.
These terms are well known in the art and general definitions apply to the present invention. For example, a filter can be a microdevice (or sub-microdevice) that can separate various components by size, and a cleaner can clean, polish, rub, and polish the intended surface. The pump may be a micro device that can transport an intended object from one position to another, and the shredder is a micro device that has a blade and a sharp blade that can make a large object into smaller pieces. It can be a device. Further, in some embodiments, the microdevice includes a cleaner, a filter, a shredder, an injector and a pump, and includes a polishing unit comprising a cleaner, a filter, a shredder and an injector, a polishing pad, or a sensor, for sampling Includes microchip, microarray for testing collected samples, data analysis unit and signal transmitter.

  In some embodiments, the microdevice can function as a microtester for continuous scanning and analysis of living biological systems for early detection and prevention of disease.

  Alternatively, the microdevice may be for in vitro applications outside of biological systems, such as outer membranes and micromechanical properties, microchemical properties, microchemical mechanical properties, microoptical properties, microacoustic properties, microbiological properties, It includes one or more properties selected from the group consisting of microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, and microsuperconducting mechanical properties, and has a size of about 1 angstrom to about 5 millimeters.

  The microdevice can also be used for medical applications such as arterial lavage and in vivo early cancer detection testing and prevention.

  Accordingly, the present invention also provides a method of using the microdevice of the present invention to wash biological material. Each method includes using the step of contacting the microdevice with a biological material, the microdevice comprising an outer membrane, a micromechanical property, a microchemical property, a microchemical property, a micro optical property, a micro acoustic property, a micro Biological characteristics, micro biochemical characteristics, micro biochemical mechanical characteristics, microelectronic biochemical mechanical characteristics, microelectrochemical mechanical characteristics, microelectromechanical characteristics, microelectromechanical characteristics, microacoustic mechanical characteristics, and microsuperconducting mechanical characteristics The microdevice is about 1 angstrom to about 5 millimeters in size, including characteristics selected from the group. Examples of biological material to be washed include, but are not limited to, mammalian veins or arteries. This cleaning can be performed, for example, by mechanical polishing, mechanical friction, chemical mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, polishing by chemical dissolution, laser cutting or a combination thereof.

  In some embodiments, the method of claim 38 includes delivering the microdevice to a general area of biological material, and optionally, local temperature, local pressure, local friction force, local surface charge, local static potential, local Measuring the potential, local surface properties, local composition or local liquid flow rate, optionally initiating the cleaning function, performing the cleaning, and optionally collecting and debris from the micro-collector cleaning Transporting and removing, and optionally collecting the debris with a microfilter and transporting and removing the debris.

  In some other embodiments, the method includes delivering the microdevice to a vein, optionally detecting and analyzing the collected data, eg, local pressure, and optionally the target location of the vein. Starting the cleaning function when reaching the target, cleaning the plaque and deposits from the vein wall at the target location, and optionally injecting the desired chemical into the occlusion site to be cleaned Softening, preventing the formation of large debris by cutting the plaque, minimizing possible damage to the veins, and optionally dissolving the microdevice after washing or filtration by hemofiltration; Optionally filtering microdevices and debris by hemofiltration during and after washing, and optionally by microdevices Further comprising the step of carrying out the purification workup.

  Yet another aspect of the invention provides a method for delivering multiple doses of an agent to a target location in vivo, each method comprising transporting a microdevice to the target location, and a first to the target location. And delivering a second dose of the drug to the target location at a desired time interval from the delivery time of the initial delivery, the microdevice comprising an outer membrane, micromechanical properties, microchemistry Characteristics, micro chemical mechanical properties, micro optical properties, micro acoustic properties, micro biological properties, micro biochemical properties, micro biochemical mechanical properties, micro electronic biochemical mechanical properties, micro electro chemical mechanical properties, micro electro mechanical properties, micro Including a property selected from the group consisting of an electromagnetic mechanical property, a microacoustic mechanical property, and a micro superconducting mechanical property; Vice is about 5 millimeters to about 1 Å in size.

  In some embodiments, each dose delivers different agents at different doses. In some other embodiments, the drug is a variety of chemicals, and delivery of the first drug increases binding selectivity with the second drug.

  Alternatively, the present invention also provides a method of using a microdevice for medical purposes, the microdevice comprising an outer membrane and micromechanical properties, microchemical properties, microchemical mechanical properties, microoptical properties, microacoustic properties, From microbiological properties, microbiochemical properties, microbiochemical mechanical properties, microelectronic biochemical mechanical properties, microelectrochemical mechanical properties, microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, and microsuperconducting mechanical properties The microdevice is from about 1 angstrom to about 5 millimeters in size, and the medical purpose is at the cellular structure or micro-organ level of the target area (up to about 500 micron scale) Drug delivery function, cutting function, removal function, polishing function, transport function, bonding machine , Diagnostics, detection function, selective protection, a target removal function, measurement function, therapeutic function of a cancer or blood-related disease is selected from the group consisting of medical auxiliary function.

  In some embodiments, the method is for cancer treatment, selectively attaching a microdevice comprising a drug delivery function to a cancer cell, and initiating an injection function of the microdevice; Injecting the drug into the cancer cells. Alternatively, the method removes unhealthy cells by selectively attaching microdevices with high light reflectance to healthy cells, performing laser treatment to destroy unhealthy cells, and processing by exposure to laser. Including the step of.

  In some embodiments, the microdevice used in these methods can include a characteristic selected from the group consisting of a signal sensing unit, a memory unit, a logic processing unit, a signal transmitter, and a microsurgery. The device performs a diagnostic, detection or measurement function, the method comprising: delivering a microdevice to a measurement target site; performing a measurement at the target site; and recording data in a memory unit. Optionally, using a logic processing function to initiate an operation; optionally performing a procedure using the microdevice; recovering the microdevice; and analyzing the recorded data Including.

  In some other embodiments, the microdevice can perform the function of diagnosing, sensing or measuring the target site, the microdevice for signal sensing unit, memory unit, signal transmitter, field decision making and microsurgery A logic unit for delivering a microdevice to a target site, performing a diagnostic function, a sensing function or a measurement function at the target site, recording data in a memory unit, and recording by the microdevice Analyzing the processed data, determining the process and type of micro-manipulation based on data analysis by the micro device and pre-programmed logic decisions, and performing the micro-manipulation at the target site.

  In still other embodiments, the microdevice includes an electrical property measurement unit and is capable of detecting cancer cells at the target site, the method comprising delivering the microdevice to the target site; Measuring one or more characteristics selected from the group consisting of surface charge, charge density, resting potential, potential, electrochemical potential, surface current, bulk current and current density at the target site. The microdevice may further include, for example, a voltage comparator having a voltage measurement sensitivity higher than 1 mV.

  In some other embodiments, the method can be used for cell detection of cancer at a target site, delivering a microdevice to the target site, and surface charge, resting potential, electrochemical potential, potential, surface current. From the group consisting of, bulk current, surface wettability, contact angle, adhesion rate, temperature, density, friction force, hardness, surface tension, trace chemical concentration, pH, liquid flow rate, pressure, optical properties, absorption, adsorption and composition Measuring one or more selected parameters on the target site.

  The microdevice of the present invention is a method known in the art, for example, an integrated circuit manufacturing method, a semiconductor manufacturing method, a mechanical manufacturing method, a chemical processing method, a synthesis method, an electrochemical processing method, a biological method. It can be produced by one or more methods selected from the group consisting of processing methods, biochemical processing methods and laser processing methods.

  Accordingly, another aspect of the present invention is the use of a microdevice to obtain real-time data and information at the cellular structure level in a non-invasive manner, for example a micro voltage comparator for measuring cell surface charges Use four-point probes and other circuit designs. Distinguishing cell surface charges can be an important factor in determining the health or unhealthy state of a cell and determining its appropriate treatment if necessary. One example is the use of such devices to measure surface electrical properties and / or bulk electrical properties, including resting potential and surface charge, to differentiate between normal cells and cancer cells.

  Yet another aspect of the present invention is the use of a microdevice to deliver a drug to a target location within the human body, distinguishing between healthy cells and unhealthy cells (eg, cancer). This can be achieved on healthy or unhealthy cells (such as cancer cells) by selective absorption or selective adsorption of microdevices. For example, to remove some of the unhealthy organs by laser surgery, microdevices with high light reflectivity can be used to selectively adsorb healthy cells, thereby removing good cells by laser treatment And / or prevent peeling.

  As used herein, the expression “or” is intended to include both “and” and “or”.

  As used herein, the term “a” and the noun include the meaning of the plural nouns.

  As used herein, a “microdevice” can be any of a wide range of materials, properties, shapes, complexity and integrations, or combinations thereof, as desired. The term has a general meaning for the application of very complex devices, from single materials to multiple subunits and multiple materials with multiple functions. The complexity envisaged by the present invention ranges from a very small single particle with the desired set of properties to a very complex integrated unit containing various functional units. For example, a simple microdevice can be a single spherical particle having a desired hardness, a desired surface charge, or a desired organic chemical that is absorbed at the surface and having a particle size on the order of 100 angstroms. A more complex microdevice can be a 1 millimeter device with all sensors, simple calculators, memory units, logic units and cutters integrated. In the former case, the particles can be formed by fume processing or colloidal precipitation processing, while devices with various components integrated can be manufactured using various integrated circuit manufacturing processes.

  The microdevice of the present invention or the microdevice used in the present invention can be sized from about 1 angstrom unit to about 5 millimeter units (eg, diameter). For example, for small target biomolecules, entities or compositions such as cell structures, DNA, bacteria, microdevices with a size of about 10 angstroms to 100 microns can be used in the present invention. Alternatively, microdevices sized about 1 micron to 5 millimeters can be used in the present invention to target relatively large biological materials such as parts of human organs. By way of example, a simple microdevice as defined herein may be a single particle having a diameter of less than 100 angstroms, and has the desired surface properties (preferential absorption or preferential adsorption on the target cell type) ( For example, surface charge or chemical coating).

  The term “absorbing” usually means a physical bond between a surface and a substance attached (in this case absorbed) to the surface. On the other hand, the word “adsorption” generally means a stronger chemical bond between the two. These properties are targeted by the desired microdevice for (a) measurements at the microscopic level, (b) target removal of unhealthy cells and (c) protection of healthy cells during treatments such as laser surgery. It is very important for the present invention because it can be used effectively against the resulting adhesion.

  As used herein, the term “chemical” generally refers to a specific active chemical (eg, a large or small compound) or a compound capable of reacting with a targeted delivery region substance.

  New microdevices, their new combinations, integration and integrated operational process flows can solve many problems in today's medicine. In particular, according to the present invention, microdevices can be used in “washing” living organs, such as veins, to prevent heart attacks, strokes and vascular occlusions due to intravenous plaque and fatty deposits.

It is a perspective view of the microdevice which can function as a microinjector, and shows the microdevice before and after the injection process is completed. Perspective view of a micro device that functions as a micro polisher A perspective view of a micro device functioning as a micro polishing machine, micro filter, micro injector, micro sensor, and micro shredder Perspective view of a microdevice that functions as a microknife Perspective view of a microdevice that functions as a microfilter Perspective view of a micro device that functions as a micro shield Perspective view of microdevice in blood vessel near plaque in blood vessel wall A perspective view of a microdevice in a blood vessel that senses a change in pressure around the plaque and initiates a microdevice cleaning function Perspective view of microdevice in blood vessel after cleaning plaque from vessel wall Enlarged perspective view of healthy cells and unhealthy (cancer) cells It is a perspective enlarged view of a healthy cell group and an unhealthy (cancer) cell group, and shows that a microdevice acts on both cells as a voltage comparator. Enlarged perspective view of healthy cells and unhealthy (cancer) cells It is a perspective enlarged view of a healthy cell group and an unhealthy (cancer) cell group, and shows that a microdevice is adsorbed or absorbed only on healthy cells. An enlarged perspective view of an integrated microdevice comprising various subunits, a microcutter, a microneedle, a memory unit, a unit for analysis and logic processing, a microsensor and a signal transmitter. A perspective view of a microdevice comprising a detection unit, a logic unit and a microinjector

  The present invention is expected to provide new microdevices for biological applications and to solve many critical problems in modern medical efforts. These problems include, for example, the pathology and prevention of many life-threatening diseases, non-invasive, microscopic and effective diagnosis of various medical conditions, and life-threatening diseases such as cancer. Includes a lack of understanding with effective targeted drug delivery systems and treatments.

  The microdevices of the present invention can be sized from about 1 angstrom to about 5 millimeters (eg, from about 1 angstrom to about 100 microns or from about 100 microns to 5 millimeters). Small microdevices (eg, about 1 angstrom to about 100 microns) obtain information and data at the cellular structure level or molecular (eg, DNA, RNA, or protein) level, especially for detection, measurement, and diagnostic purposes While large microdevices (eg, about 100 microns to about 5 millimeters) can be used for mechanical or surgical manipulation of human organs or tissues, except for manipulation at the cellular structure level. .

  As described herein, the general term “microdevice” refers to a wide range of materials, properties, shapes, complexity and integration, or combinations thereof. The complexity envisaged by the present invention ranges from a very small single particle with the desired set of properties to a very complex integrated unit containing subunits of various functions. For example, a simple microdevice can be a single spherical particle having a desired hardness, a desired surface charge, or a desired organic chemical that is absorbed at the surface and having a particle size on the order of 100 angstroms. More complex microdevices can be 1 millimeter devices that are all integrated with sensors, simple calculators, storage units, logic units and cutters. In the former case, the particles can be formed, for example, by fume processing or colloidal precipitation, while devices in which various components are integrated can be manufactured using various integrated circuit manufacturing processes.

  The microdevice of the present invention can have various designs, structures and functionalities. The micro device is, for example, a voltage comparator, a four-point probe, a calculator, a logic circuit, a storage device, a micro cutter, a micro hammer, a micro shield, a micro die, a micro pin, a micro knife, a micro needle, a micro thread holder, a micro tweezer, Micro light absorber, micro mirror, micro wheeler, micro filter, micro chopper, micro shredder, micro pump, micro absorber, micro signal detector, micro drill, micro sucker, micro tester, micro container, signal transmitter, signal generation , A friction force sensor, a charge sensor, a temperature sensor, a hardness detector, a sound wave generator, a light wave generator, a heat generator, a micro refrigerator, and a charge generator.

  As disclosed herein, the functionality and range of applications using microdevices can be very broad due to various properties, high flexibility, and integration and miniaturization capabilities.

  In addition, it should be noted that advances in manufacturing technology are now extremely feasible and cost-effective for manufacturing various microdevices and integrating various functions in microdevices. . A typical human cell size is about 10 microns. Using state-of-the-art integrated circuit fabrication techniques, the minimum feature size defined by a microdevice can be as small as 0.1 microns. Thus, the microdevice of the present invention is ideal for biological applications.

  Regarding materials for microdevices, the general principle is a material that is compatible with biological material. The microdevice of the present invention or any subunit thereof is manufactured because the contact time with biological material (eg, biomolecules such as DNA, RNA or protein, cells, groups of cells, tissues or organs) may vary depending on the application. In order to do so, it is possible to select various materials. In some cases, the material may be dissolved at a specific pH in a controlled manner and thereby selected as a suitable material. Other considerations include cost, simplicity, ease of use and practicality. With significant advances in microfabrication technology such as integrated circuit manufacturing technology, highly integrated devices with a minimum feature size on the order of 0.1 microns are now cost-effective and can be marketed. One example is the design and manufacture of microelectromechanical devices (MEMS), which are currently used in various applications in the integrated circuit industry.

  The following description includes some examples of the use of various types of microdevices of the present invention that can be used for novel biological applications.

Detection, measurement and diagnosis:
Prior to the present invention, it appears that there were no probes that measured microscopic properties in real time at the cellular level of living organs (in vivo). The novel microdevice provided by the present invention can measure the cell characteristics of a living organ. Information from measurements is required to be searched in real time for use as a diagnostic tool.

  For example, the microdevice of the present invention can be used to detect cancer cells in a living organ by a non-invasive method. FIG. 10 shows a region of the human body with many healthy (or normal) cells “a” 39 and many unhealthy (or abnormal) cells “b” 40. Electrical properties such as the charge and resting potential of the healthy cell “a” 39 are different from the unhealthy cell “b” 40. Initially, a microdevice with a voltage comparator is calibrated by measuring the surface charge (or voltage) on known healthy cells. Next, as shown in FIG. 11, for a region containing healthy cells 39 and unhealthy cells 40, a microdevice 41 comprising a voltage comparator 42 is used to scan that region. Unhealthy cells 40 can be easily differentiated from healthy cells 39 by comparing cell surface voltages (differences in charge or potential). Such a microdevice 41 can be easily expanded to differentiate cancer cells by integrating a voltage comparator, a logic circuit unit, and a microinjector (needle) capable of specifically delivering an anticancer agent to the cancer cells. The function of measuring and treating can be performed.

Drug delivery:
So far, laboratory tests using mice may have been successful, but many cancer therapeutics have not shown the promising results expected in human clinical trials. There may be significant problems with successful and effective drug delivery to target cancer cells. Since such drugs are often administered to the human body by tablet or injection, it is believed that there are significant problems with drugs that reach the targeted cancer site. Even if the drug can reach the target site, its potency (concentration) and chemical composition will change, which may be partially or totally ineffective. Increasing the amount of drug delivered in this way can increase side effects and cause increased mortality.

  In the present invention, a new effective targeted drug delivery system allows for the correction of the above problems. As shown in FIG. 15, a micro device 64 including a detection unit 62, a logic unit 63, and a micro injector 61 is used. The microdevice 64 is designed to selectively preferentially absorb (or preferentially adsorb) only unhealthy cells. Alternatively, the sensor 62 can detect unhealthy cells according to measurements of desired physical, chemical, electrical, and biological properties of the cells being scanned and is attached to the detected unhealthy cells. When the microdevice 64 adheres to an unhealthy cell, the microinjector 61 injects one or more anticancer agents into the cancer cell. In order to ensure that healthy cells are not injected due to an attachment error, logic unit 63 can be used to make a correct decision based on data received from the attached cells by detection unit 62. Since this method is a targeted method using an anticancer agent delivered directly to unhealthy cells, its effectiveness is expected to greatly improve the standard treatments conventionally used for current cancer treatment.

Washing:
Another main area of focus of the present invention is a new kind of microdevice for biological “washing”, in particular for “washing” of human arteries and veins. FIG. 7 shows the vessel wall 30, the microdevice 32 moving in the direction 33, the thrombus 36, the diastolic blood pressure P1 34 and the diastolic blood pressure P2 35. In this type of application, the present invention is a microdevice 32 having at least one cleaner to be deposited. A more complete microdevice consists of at least one sensor, one cleaner, one microfilter, one injector, one shredder and one pump.

  As shown in FIG. 8, the microdevice 32 with integrated sensing (for local pressure measurement) and lavage 37 functions can be used for arterial and venous lavage applications. In this case, the local pressure is even higher and the plaque 36 is located at P2 35 within the vessel wall 30. The device is moving in the direction 33 towards the plaque 36 in the vessel wall 30. As device 32 approaches the plaque, it senses this increase in local pressure and begins to deploy cleaning function 37.

  FIG. 9 shows the blood vessel wall 30 after the microdevice 32 with the cleaning function 37 has cleaned the plaque from the region 38 in the blood vessel wall 30. This is just one of many examples, and the microdevice disclosed in this application can be used as a “high performance” device for non-invasive, real-time biological applications.

In FIG. 3, a more precise micro device 17 is disclosed, which comprises a cleaner arm 8, a cleaner 9, a sensor 15, micro filters 13 and 14, a micro shredder 11 and a micro injector 16.
This design is aimed at facilitating the cleaning process and ensuring that the debris is cleaned up into smaller pieces that are completely removed and do not cause thrombi in other areas of the human body. Cleaners are usually abrasive or frictional, and filters are used to filter washed debris and move it to other parts of the human body without causing thrombus problems. The injector is used to dispense a lysing agent that dissolves debris from the cleaner portion of the microdevice and can also deliver the drug to facilitate a “cleaning” (polishing) process. The micro-shredder 11 can be used to break up relatively large pieces from the cleaning (if any) operation. More specifically, the cleaning unit may be a polishing pad 9 made from a polymer material of the desired roughness for polishing or rubbing. In order to reduce the mechanical force and prevent the plaque from being cut into large pieces, the polishing solution can be added to the micropolishing site using the injector 16. In a preferred method, the plaque is polished in a layer-by-layer process (several monolayers having a thickness of about 10 angstroms) while controlling the removal rate. A balanced chemical mechanical polishing process is preferred, and when surface chemical reactions and surface mechanical wear are present, the mechanical wear is controlled to a sufficiently low level so as not to cause plaque cutting. On the other hand, the microfilters 13 and 14 are used to ensure that no large debris remains in the cleaning area and areas that cause damage to other parts of the human body. For patients whose deposits tend to increase in veins, they need to be cleaned using the method disclosed regularly to reduce the risk of heart attacks and strokes and reduce the difficulty of subsequent cleaning procedures.

  Since the diameter of the main artery is usually a few millimeters (diameter about 2 mm to 4 mm), the size of the microdevice for this type of cleaning application (main artery cleaning) is about 10 microns to less than 2 mm For example, from about 100 microns to about 1.5 millimeters.

Targeted treatment:
The microdevice disclosed in the present invention is ideally suited for targeted therapies that remove or destroy unhealthy cells or organ parts while minimizing damage to healthy cells or organ parts. This can be done very selectively, is non-invasive and can be done in a microscopic manner.

  FIG. 12 shows a region of the human body with many healthy cells 39 and many unhealthy cells 40. In FIG. 13, for use in laser surgery using an optical cutting process, healthy cells 39 are first covered with a microdevice 43 (referred to as a microshield) with high light reflectivity. Next, unhealthy cells 40 such as cancer cells are removed by optical cutting, while healthy cells 39 are protected by a microshield 43. This selective attachment of the microshield 43 to the healthy cells is due to the surface adsorption between the microdevice and the healthy cells by the microdevice that senses the desired properties such as processing and / or charge attraction of the microdevice (or Surface absorption). For example, the microdevice can be designed or programmed to attach only to healthy cells by surface charge measurements, subsequent logic decisions and operations, as shown above and described in detail in FIG.

  Another embodiment of the present invention for targeted therapy is the use of an integrated microdevice with sensing, logic processing and injection functions. The microdevice first uses a sensing function that indicates the target. The microdevice then attaches to the target. Ultimately, the microdevice injects an anticancer agent into the cancer cells.

Micro surgery:
As described herein, a variety of microdevices that can perform a wide range of surgical functions can be used to achieve well-defined goals. Some examples of microdevices that can perform microsurgery are shown in FIGS.

  FIG. 1 shows a microdevice 6 before the microsurgery is started and a microdevice 7 after the microsurgery is started. The device 6 consists of an outer membrane 1, a detection unit 2, a lower plate 3 and a region 4, and can store various drugs before the start of microsurgery. The device 7 in which the microsurgery has started has a region 5 which is emptied when the lower board 3 is pushed vertically to release the contents of the region 4. FIG. 2 shows a microdevice 10 with a polishing / scrubber function 9 attached to an extension arm 8 outside the outer membrane 1. FIG. 4 shows a microdevice 20 comprising an outer membrane 1 and a vertical fastener 19 having a blade tip 18. FIG. 5 shows a microdevice 25 comprising a top surface 24, an outer membrane 21, and a series of openings 22 in the top surface 24, the openings 22 extending into a conduit 23 extending to the bottom surface 26 throughout the microdevice 25. FIG. 6 shows a micro device 29 including a main body 27, and a reflection portion 28 is attached to the upper portion of the main body 27.

  It should be emphasized that for practical surgical applications, an integrated microdevice with multiple functional elements and functionality is the preferred choice and is the most effective universal instrument for surgery. The obvious advantages of these “high performance” devices disclosed in the present invention are that they perform surgery at a microscopic level in a minimally invasive manner, are highly accurate, highly selective, and provide healthy cells and organs. To minimize damage.

An example of an integrated microdevice is at least one sensor, one memory unit, one logic processing unit, one signal transmitter, one signal receiver, at least one microinjector, a plurality of microknives, a plurality of micros Including a needle, at least one microtweezers and at least one microthread holder. Such integrated microdevices can perform several basic surgeries. An example of an integrated microdevice is shown in FIG.
FIG. 14 shows an integrated microdevice 43 comprising an outer membrane 44 and a detection unit 47 attached to a detection arm 48 connected to the memory unit 50 via a path 49, the memory unit 50 being a signal transmitter 45. Connected via a path 51 to an analysis / logic unit 52 mounted via a path 46 to the path 52, the unit 52 is routed 53 to a microneedle unit 55 reaching the outside via a needle 54 extending through the outer membrane 44. And is attached via a path 56 to a microcutter unit 57 comprising an extension arm 58 having a cut end 59.

  In accordance with the invention disclosed herein, a microdevice for the detection, treatment, and prevention of biological diseases, particularly at the microscopic level, for biological applications, is provided and described in detail herein. It is clear that the needs and advantages to be fully met. While particular embodiments have been presented herein, those skilled in the art will recognize that all modifications and variations can be made without departing from the spirit of the invention. Accordingly, the present invention is not intended to be limited by the description herein. Any combination of the microdevices disclosed in the present invention and any obvious extension of the microdevice for biological applications is within the scope of the present invention. In addition, any integration of the disclosed microdevices for treatment including disease detection, prevention and treatment of the human body is also disclosed herein. Accordingly, the present invention is intended to embrace all configurations suitable for achieving the same objective, and all such variations and modifications within the scope of the claims.

  The contents of all documents filed at the same time as the present specification and published together with the present specification are hereby incorporated by reference. All features disclosed in this specification (including the claims, abstract and drawings) of this application may be replaced by other features serving the same, equivalent or similar purposes unless otherwise specified. Thus, unless expressly stated, each feature disclosed is one example of a set of common equivalent or similar features.

  Any element of a claim that does not specify a “means for performing” a particular function or a “step for performing” a particular function or a “step” for performing a particular function is claimed in US Pat. It is not interpreted as a form of “means” or “process” defined in the sixth paragraph of 112 shape.

  All publications referenced above are incorporated herein by reference in their entirety.

Claims (53)

A microdevice for use in biological systems,
Outer membrane, micro mechanical property, micro chemical property, micro chemical mechanical property, micro optical property, micro acoustic property, micro biological property, micro bio chemical property, micro bio chemical mechanical property, micro electron bio chemical mechanical property, micro electron A property selected from the group consisting of chemical mechanical properties, microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, microthermomechanical properties, microthermoelectric properties, microthermoelectromechanical properties and microsuperconducting mechanical properties The microdevice is about 1 to 5 millimeters in size. Micro mechanical properties, micro chemical properties, micro chemical mechanical properties, micro optical properties, micro acoustic properties, micro biology properties, micro electro mechanical properties, micro electro mechanical properties, micro acoustic mechanical properties, micro thermo mechanical properties, micro thermo chemical machinery The microdevice according to claim 1, comprising two characteristics selected from the group consisting of characteristics, microthermoelectric characteristics, microthermoelectromechanical characteristics, and microsuperconducting mechanical characteristics. Includes properties selected from the group consisting of charged surfaces, potentials, chemical potentials, geometric integrity, electromagnetics, ion gradients, thermal gradients, surface tensions, mechanical forces, electrochemical potentials, attractive forces related to physical forces The microdevice according to claim 1. The microdevice according to claim 1, wherein normal cells and cancer cells can be differentiated. Measure the microscopic characteristics of organ structure and cell structure, diagnose organ and cell structure at microscopic level, deliver desired chemicals to organ structure and cell structure at microscopic level, microscopically The microdevice according to claim 1, wherein a desired drug can be delivered to the organ structure and cell structure at a level, and the selected organ structure and cell structure can be manipulated at a microscopic level. The microdevice according to claim 5, wherein the function is performed in a non-invasive manner. The micro device according to claim 5, wherein the function is executed in real time. Surface charge, static potential, electrochemical potential, potential, surface wettability, contact angle, adhesion rate, temperature, density, friction force, hardness, surface tension, trace chemical concentration, hydrophobicity, hydrophilicity, pH, liquid flow rate The microdevice according to claim 5, wherein at least one characteristic selected from the group consisting of pressure, optical characteristics, absorption, adsorption and composition can be measured. The microdevice according to claim 1, comprising a satellite positioning system (GPS), a signal transmitter, a signal receiver, a micromotor, a micropropeller, an RF communication chip, a logic circuit, and a memory circuit. Chemical delivery function, controlled chemical delivery function, mechanical motion, controlled mechanical motion, selective absorption, selective adsorption, detection at microscopic level, electromechanical timed motion, controlled electromechanical motion, controlled electrochemical mechanical motion Controlled electronic biological action, Controlled electrochemical biological action, Controlled electrochemical biological action, Controlled electrochemical biomechanical action, Action initiated by detected signal, Action initiated by external command The microdevice according to claim 1, comprising a function selected from the group consisting of: The microdevice of claim 1 having a preprogrammed initiation function for an operation selected from the group consisting of chemical delivery to organic structures, mechanical force operation, charge injection, light emission, voltage application, cooling and heating. The initiating functions are: charge detected by the device, resting potential, potential, electrochemical potential, surface current, bulk current, surface wettability, adhesion, hydrophobicity, hydrophilicity, fluidity, electric field, magnetic field, sound field The microdevice according to claim 11, wherein the microdevice is used by using from a group of parameters selected from the group consisting of: temperature, light wavelength and / or light intensity, friction force and coefficient of friction, hardness, pressure and external signal. The microdevice according to claim 1, wherein the microdevice has a dissolution ability in a target pH range for 30 seconds to 3 days. The microdevice according to claim 1, comprising a material selected from the group consisting of polymers, organic materials and inorganic materials that are relatively compatible with organic tissue. The microdevice according to claim 1, wherein the size is about 1 to 100 millimeters. The microdevice according to claim 1, wherein the size is about 1 to 100 microns. The microdevice according to claim 1, comprising one material in which a plurality of subdevices are integrated in one unit having at least one functionality. The microdevice according to claim 1, comprising a material selected from the group consisting of a polymer, an organic substance, a biological substance, a biochemical substance, an inorganic conductor, an inorganic semiconductor, an inorganic insulator, and a ceramic. The micro device according to claim 18, wherein the biological material is selected from the group consisting of artificial biological material, natural biological material, cultured biological material, and a combination of natural biological material and artificial biological material. The microdevice according to claim 17, wherein the size is about 0.01 micron to 5 millimeters. Integrated micro comprising one function selected from the group consisting of detection function, detection function, measurement function, calculation function, analysis function, diagnosis function, logic processing (decision making) function, transmission function and surgical function or surgical function The microdevice according to claim 1, which is a device. Voltage comparator, 4-point probe, calculator, logic circuit, memory unit, micro cutter, micro hammer, micro shield, micro die, micro pin, micro knife, micro needle, micro thread holder, micro tweezers, micro light absorber, micro Mirror, Micro Wheeler, Micro Filter, Micro Chopper, Micro Shredder, Micro Pump, Micro Absorber, Micro Signal Detector, Micro Drill, Micro Suction Cup, Micro Tester, Micro Container, Micro Puller, Signal Transmitter, Signal Generator, Friction Force sensor, charge sensor, temperature sensor, hardness detector, sound wave generator, light wave generator, thermomechanical device, thermochemical mechanical device, thermoelectromechanical device, heat generator, micro refrigerator, micro signal transmission The micro device according to claim 1 including a hardware selected from the group consisting of micro-signal receiver and a charge generator. Selected from the group consisting of integrated circuit manufacturing methods, semiconductor manufacturing methods, mechanical manufacturing methods, chemical processing methods, synthesis methods, electrochemical processing methods, biological processing methods, biochemical processing methods and laser processing methods. The microdevice according to claim 1 manufactured by a method. The micro device according to claim 1, comprising a cleaner, a filter, a shredder, an injector, and a pump. The microdevice according to claim 1, comprising a cleaner, a filter, a shredder, or an injector. The micro device according to claim 1, further comprising a polishing unit including a polishing pad. The microdevice according to claim 1, wherein the size is 10 microns to 2 millimeters. The microdevice according to claim 1, wherein the size is 100 microns to 1.5 millimeters. The microdevice according to claim 1, wherein the microdevice is a microtester for continuously scanning and analyzing a living biological system for early detection and prevention of a disease. The microdevice according to claim 1, comprising a sensor, a microchip for sampling, a microarray for testing the collected sample, a data analysis unit, or a signal transmitter. The microdevice according to claim 1, wherein the size is about 1 to 100 microns. The microdevice according to claim 1, wherein the size is about 10 microns to 5 millimeters. The microdevice according to claim 1, wherein the size is about 2 angstroms to 500 microns. The microdevice according to claim 1, which is used for arterial washing. The microdevice according to claim 1, which is used for early cancer detection test and prevention in vivo. A method of using a microdevice to wash biological material, comprising:
Contacting the microdevice with the biological material;
The microdevice is composed of an outer membrane, micromechanical properties, microchemical properties, microchemical mechanical properties, microoptical properties, microacoustic properties, microbiological properties, microbiochemical properties, microbiochemical mechanical properties, microelectronic biochemistry. Mechanical properties, microelectrochemical mechanical properties, microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, microthermomechanical properties, microthermochemical mechanical properties, microthermoelectric properties, microthermoelectromechanical properties and microsuperconducting machinery A method selected from the group consisting of properties, wherein the size is between about 1 angstrom and 5 millimeters. 37. The method of claim 36, wherein the biological material is a mammalian vein or artery. Delivering the microdevice to the general area of the biological material, and optionally, local temperature, local pressure, local friction, local surface charge, local static potential, local potential, local surface properties, local composition or local liquid Measuring the flow rate, optionally initiating the cleaning function, performing the cleaning, optionally collecting, transporting and removing debris from the microcollector cleaning, and optionally microfiltering Collecting the debris and transporting it away. Delivering a microdevice to the vein, optionally detecting and analyzing the collected data, eg, local pressure, and optionally initiating a lavage function upon reaching the target location of the vein Washing plaque and deposits from the vein wall at the target location, and optionally injecting the desired chemical into the occlusion site to be washed, softening the plaque to be washed, and cutting the plaque Preventing the formation of large debris and minimizing possible damage to the veins, and optionally lysing the microdevice after washing or after filtration by hemofiltration, and optionally during washing And filtering the microdevice and debris by blood filtration after washing, and optionally after washing by the microdevice The method of claim 36 including the step of implementing the management. The cleaning is performed by mechanical polishing, mechanical friction, chemical mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, polishing by chemical dissolution, laser cutting, or a combination thereof. Method. A method for delivering multiple doses of a drug to a target location in vivo comprising:
Transporting a microdevice to the target location; delivering a first agent to the target location; and delivering a second dose of the agent to the target location at a desired time interval from a delivery time of the initial delivery. Including the steps of:
The microdevice is composed of an outer membrane, micromechanical properties, microchemical properties, microchemical mechanical properties, microoptical properties, microacoustic properties, microbiological properties, microbiochemical properties, microbiochemical mechanical properties, microelectronic biochemistry. Mechanical properties, microelectrochemical mechanical properties, microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, microthermomechanical properties, microthermochemical mechanical properties, microthermoelectric properties, microthermoelectromechanical properties and microsuperconducting machinery A method selected from the group consisting of properties, wherein the size is between about 1 angstrom and 5 millimeters. 42. The method of claim 41, wherein each dose delivers a different drug at a different dose. 42. The method of claim 41, wherein the drug is a variety of chemicals and delivery selectivity of the first drug increases binding selectivity with the second drug. A method of using a microdevice for medical purposes,
The microdevice is composed of an outer membrane, micromechanical properties, microchemical properties, microchemical mechanical properties, microoptical properties, microacoustic properties, microbiological properties, microbiochemical properties, microbiochemical mechanical properties, microelectronic biochemistry. Including a property selected from the group consisting of mechanical properties, microelectrochemical mechanical properties, microelectromechanical properties, microelectromechanical properties, microacoustic mechanical properties, and microsuperconducting mechanical properties, and having a size of about 1 angstrom to 5 millimeters And
The medical purpose includes a drug delivery function at a cell structure or a micro-organ level in a target region, a cutting function, a removing function, a polishing function, a transporting function, a joining function, a diagnostic function, a detecting function, a selective protecting function, a target removing function, The method is selected from the group consisting of a measurement function and a medical assistance function. The method comprises the steps of selectively attaching to a cancer cell a microdevice having a drug delivery function used for cancer treatment, initiating an injection function of the microdevice, and injecting a drug into the cancer cell. 45. The method of claim 44, comprising: Selectively attaching a micro device with high light reflectance to healthy cells; performing laser treatment to destroy unhealthy cells; and removing unhealthy cells by treatment by exposure to the laser. 45. The method of claim 44. The microdevice includes a characteristic selected from the group consisting of a signal sensing unit, a memory unit, a logic processing unit, a signal transmitter, and a microsurgery, the microdevice performing a diagnostic, sensing or measuring function, The method includes delivering the microdevice to a measurement target site, performing a measurement at the target site, recording data in a memory unit, and optionally performing operations using the logic processing function. 45. The method of claim 44, comprising the steps of: initiating; optionally, performing a surgery using the microdevice; retrieving the microdevice; and analyzing the recorded data. The micro device performs a function of diagnosing, sensing or measuring a target site, and the micro device includes a signal detection unit, a memory unit, a signal transmitter, a logic unit for field decision making and micro surgery, A method of delivering the microdevice to the target site, performing a diagnostic function, a sensing function or a measuring function at the target site; recording data in a memory unit; and the data recorded by the microdevice 45. determining a process and type of micro manipulation based on data analysis by the micro device and pre-programmed logic determination; and performing micro manipulation on the target site. The method described in 1. The microdevice includes an electrical property measurement unit and is capable of detecting cancer cells at a target site, the method comprising delivering the microdevice to the target site; and a surface charge at the target site; 45. Measuring the one or more properties selected from the group consisting of charge density, resting potential, potential, electrochemical potential, surface current, bulk current and current density. 50. The method of claim 49, wherein the microdevice further comprises a voltage comparator. 51. The method of claim 50, wherein the voltage comparator has a voltage measurement sensitivity greater than 1 mV. The method is used for cell detection of cancer at a target site, delivering the microdevice to the target site, surface charge, resting potential, electrochemical potential, potential, surface current, bulk current, surface wettability. , Contact angle, adhesion rate, temperature, density, friction force, hardness, compression rate, rigidity rate, acoustic properties, surface tension, trace chemical concentration, pH, liquid flow rate, pressure, optical properties, absorption, adsorption and composition 45. measuring one or more parameters selected from a group on the target site. A microdevice for use outside a biological system,
Outer membrane, micro mechanical properties, micro chemical properties, micro chemical mechanical properties, micro optical properties, micro acoustic properties, micro biological properties, micro electro mechanical properties, micro electro mechanical properties, micro acoustic mechanical properties, micro superconducting mechanical properties A microdevice characterized in that it has one characteristic selected from the group consisting of and has a size of about 1 angstrom to 5 millimeters.

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