Apparatus for Improved Disease Detection

Abstract

The invention relates to apparatus for detecting a disease in a biological subject, which comprises a delivery system and at least two sub-equipment units which are combined or integrated in the apparatus, wherein the delivery system is capable of delivering the biological subject to at least one of the sub-equipment units and each sub-equipment unit is capable of detecting at least one property of the biological subject. Also related to the invention are methods for detecting a disease with the apparatus.

What is claimed is: 
     
         1 . An apparatus for detecting a disease in a biological subject, comprising a delivery system and at least two sub-equipment units which are combined or integrated in the apparatus, wherein the delivery system is capable of delivering the biological subject to at least one of the sub-equipment units and each sub-equipment unit is capable of detecting at least one property of the biological subject. 
     
     
         2 . The apparatus of  claim 1 , wherein at least one of the sub-equipment units comprises a first layer of material having an exterior surface and an interior surface, wherein the interior surface defines an inter-unit channel in which the biological subject flows through the sub-equipment unit. 
     
     
         3 . The apparatus of  claim 2 , wherein at least one of the sub-equipment units further comprises a first sorting unit capable of detecting a property of the biological subject at the microscopic level and sorting the biological subject by the detected property; a first detection unit capable of detecting the same or different property of the sorted biological subject at the microscopic level; wherein the first sorting unit and the first detection unit are integrated into the first layer of material and positioned to be at least partially exposed in the intra-unit channel. 
     
     
         4 . The apparatus of  claim 3 , wherein the sub-equipment further comprises a second sorting unit, wherein the biological subject flows by or through the first sorting unit before reaching the second sorting unit, and the second sorting unit is capable of detecting the same or different property of the biological subject as the first sorting unit and sorts the biological subject by the property it detects. 
     
     
         5 . The apparatus of  claim 3 , wherein the sub-equipment further comprises a second detection unit, wherein the biological subject flows by or through the first detection unit before reaching the second detection unit, and the second detection unit is capable of detecting the same or different property of the biological subject as the first detection unit. 
     
     
         6 . The apparatus of  claim 3 , wherein a portion of the biological subject flowing through the sorting unit continues to flow to the detection unit, while the rest of the biological subject is directed to another direction for separate disposal. 
     
     
         7 . The apparatus of  claim 1 , wherein each property to be detected by a sub-equipment unit or a detection unit or a sorting unit is independently a thermal, optical, acoustical, biological, chemical, physical-chemical, electro-mechanical, electro-chemical, electro-chemical-mechanical, bio-physical, bio-chemical, bio-mechanical, bio-electrical, electro-optical, bio-electro-optical, bio-thermal optical, electro-chemical optical, bio-physical-chemical, bio-electro-physical, bio-electro-mechanical, bio-electro-chemical, bio-chemical-mechanical, bio-electro-physical-chemical, bio-electro-physical-mechanical, bio-electro-chemical-mechanical, electric, magnetic, electro-magnetic, physical, or mechanical property of the biologic subject or cells contained therein. 
     
     
         8 . The apparatus of  claim 7 , wherein the thermal property is temperature or vibrational frequency; the optical property is optical absorption, optical transmission, optical reflection, optical-electrical property, brightness, or fluorescent emission; the radiation property is radiation emission, signal triggered by radioactive material, or information probed by radioactive material; the chemical property is pH value, chemical reaction, bio-chemical reaction, bio-electro-chemical reaction, reaction speed, reaction energy, speed of reaction, oxygen concentration, oxygen consumption rate, ionic strength, catalytic behavior, chemical additives to trigger enhanced signal response, bio-chemical additives to trigger enhanced signal response, biological additives to trigger enhanced signal response, chemicals to enhance detection sensitivity, bio-chemicals to enhance detection sensitivity, biological additives to enhance detection sensitivity, or bonding strength; the physical property is density, shape, volume, or surface area; the electrical property is surface charge, surface potential, resting potential, electrical current, electrical field distribution, surface charge distribution, cell electronic properties, cell surface electronic properties, dynamic changes in electronic properties, dynamic changes in cell electronic properties, dynamic changes in cell surface electronic properties, dynamic changes in surface electronic properties, electronic properties of cell membranes, dynamic changes in electronic properties of membrane surface, dynamic changes in electronic properties of cell membranes, electrical dipole, electrical quadruple, oscillation in electrical signal, electrical current, capacitance, three-dimensional electrical or charge cloud distribution, electrical properties at telomere of DNA and chromosome, capacitance, or impedance; the biological property is surface shape, surface area, surface charge, surface biological property, surface chemical property, pH, electrolyte, ionic strength, resistivity, cell concentration, or biological, electrical, physical or chemical property of solution; the acoustic property is frequency, speed of acoustic waves, acoustic frequency and intensity spectrum distribution, acoustic intensity, acoustical absorption, or acoustical resonance; the mechanical property is internal pressure, hardness, flow rate, viscosity, fluid mechanical properties, shear strength, elongation strength, fracture stress, adhesion, mechanical resonance frequency, elasticity, plasticity, or compressibility. 
     
     
         9 . The apparatus of  claim 2 , wherein at least one of the sub-equipment units comprises a first sensor positioned to be partially in the inter-unit channel of the sub-equipment unit and capable of detecting a property of the biological subject at the microscopic level. 
     
     
         10 . The apparatus of  claim 9 , wherein the sorting unit and the detection unit each comprise one or more sensors positioned to be partially in the inter-unit channel and capable of detecting a property of the biological subject at the microscopic level, wherein the property to be detected by the sensors in the sorting unit and the detection unit can be the same or different; and
 wherein each sensor is optionally a thermal sensor, optical sensor, acoustical sensor, biological sensor, chemical sensor, electro-mechanical sensor, electro-chemical sensor, electro-optical sensor, electro-thermal sensor, electro-chemical-mechanical sensor, bio-chemical sensor, bio-mechanical sensor, bio-optical sensor, electro-optical sensor, bio-electro-optical sensor, bio-thermal optical sensor, electro-chemical optical sensor, bio-thermal sensor, bio-physical sensor, bio-electro-mechanical sensor, bio-electro-chemical sensor, bio-electro-optical sensor, bio-electro-thermal sensor, bio-mechanical-optical sensor, bio-mechanical thermal sensor, bio-thermal-optical sensor, bio-electro-chemical-optical sensor, bio-electro-mechanical optical sensor, bio-electro-thermal-optical sensor, bio-electro-chemical-mechanical sensor, physical sensor, mechanical sensor, piezo-electrical sensor, piezo-electro photronic sensor, piezo-photronic sensor, piezo-electro optical sensor, bio-electrical sensor, bio-marker sensor, electrical sensor, magnetic sensor, electromagnetic sensor, image sensor, or radiation sensor;   wherein the thermal sensor comprises a resistive temperature micro-sensor, a micro-thermocouple, a thermo-diode and thermo-transistor, and a surface acoustic wave (SAW) temperature sensor; the image sensor comprises a charge coupled device (CCD) or a CMOS image sensor (CIS); the radiation sensor comprises a photoconductive device, a photovoltaic device, a pyro-electrical device, or a micro-antenna; the mechanical sensor comprises a pressure micro-sensor, micro-accelerometer, flow meter, viscosity measurement tool, micro-gyrometer, or micro flow-sensor; the magnetic sensor comprises a magneto-galvanic micro-sensor, a magneto-resistive sensor, a magneto diode, or magneto-transistor; the biochemical sensor comprises a conductimetric device, a bio-marker, a bio-marker attached to a probe structure, or a potentiometric device.   
     
     
         11 . The apparatus of  claim 9 , wherein at least one sensor is a probing sensor and can apply a probing or disturbing signal to the biological subject. 
     
     
         12 . The apparatus of  claim 11 , wherein at least another sensor, different from the probing sensor, is a detection sensor and detects a response from the biological subject upon which the probing or disturbing signal is applied. 
     
     
         13 . The apparatus of  claim 3 , wherein the sorting unit or the detection unit comprises two panels, at least one of the two panels is fabricated by microelectronic technologies and comprises a read-out circuitry and a sensor, and the sensor is positioned on the interior surface which defines the inter-unit channel. 
     
     
         14 . The apparatus of  claim 13 , wherein the sorting unit or the detection unit further comprises two micro-cylinders that are placed between and bonded with the two panels, wherein each of the micro-cylinders is solid, hollow, or porous, and optionally fabricated by microelectronics technologies;
 the micro-cylinders are solid and at least one of them comprises a sensor fabricated by microelectronics technologies;   the sensor in the micro-cylinder applies a probing signal to the biological subject; or   at least one of the micro-cylinders comprises at least two sensors fabricated by microelectronics technologies, every two of the at least two sensors are so located in the micro-cylinder to form an array of the sensors on the panel, and optionally the two sensors in the micro-cylinder are optionally apart by a distance ranging from 0.1 micron to 500 microns, from 0.1 micron to 50 microns, form 1 micron to 100 microns, from 2.5 microns to 100 microns, or from 5 microns to 250 microns, and optionally at least one of the panels comprises at least two sensors that are arranged in at least two arrays each separated by at least a micro sensor in a cylinder.   
     
     
         15 . The apparatus of  claim 2 , wherein the interior surface defines at least one additional inter-unit channel for transporting and sorting or detecting the biological subject, and at least one of the sub-equipment units has numerous inter-unit channels for transporting and sorting or detecting the biological subject, and the inter-unit channel has a diameter or height or width ranging from 0.1 micron to 150 microns, from 0.5 micron to 5 microns, from 1 micron to 2.5 microns, from 3 microns to 15 microns, from 5 microns to 25 microns, from 5 microns to 50 microns, from 25 microns to 50 microns, or from 50 microns to 80 microns; and the inter-unit channel has a length ranging from 0.5 micron to 50,000 microns. 
     
     
         16 . The apparatus of  claim 3 , wherein the sub-equipment unit or the sorting unit or the detection unit comprises and is capable of releasing a bio-marker, an enzyme, a protein, a light emitting component, an radio-active material, a dye, a polymer component, an organic component, a catalyst, an oxidant, a reducing agent, an ionic component, a nano-particle, a magnetic particle, or a nano-particle attached to a bio-marker, or a combination thereof, for mixing with and sorting or detecting the biological subject. 
     
     
         17 . The apparatus of  claim 16 , wherein the nano-particle attached to a bio-marker is a magnetic nano-particle; and one or more magnetic nano-particles are mixed with the biological subject for separating and detecting the biological subject, or
 the bio-marker is attached with a light emitting item and mixed with the biological subject, wherein the light emitting item optionally comprises a florescence generating component; the mixed biological subject flows through an inter-unit channel; a signal of the mixed biological subject is detected and collected by a sensor in a sorting or detection unit; and the signal is an electrical, magnetic, electromagnetic, thermal, optical, acoustical, biological, chemical, electro-mechanical, electro-chemical, electro-optical, electro-thermal, electro-chemical-mechanical, bio-chemical, bio-mechanical, bio-optical, bio-thermal, bio-physical, bio-electro-mechanical, bio-electro-chemical, bio-electro-optical, bio-electro-thermal, bio-mechanical-optical, bio-mechanical thermal, bio-thermal-optical, bio-electro-chemical-optical, bio-electro-mechanical-optical, bio-electro-thermal-optical, bio-electro-chemical-mechanical, physical or mechanical signal, or a combination thereof.   
     
     
         18 . The apparatus of  claim 3 , wherein the biological subject flows through the first inter-unit channel and, after the sorting unit, is separated into a suspected component and an unsuspected component, and the two components continue to flow through the inter-unit channel in two different directions. 
     
     
         19 . The apparatus of  claim 18 , wherein the sub-equipment unit further comprises one or more additional inter-unit channels each of which is defined by the interior surface of the first or additional layer of material and is integrated to the first channel, and the separated suspected component or unsuspected component flows through the additional channel(s) for further separation; and wherein the sub-equipment unit optionally comprises a sorting unit or a detection unit attached to the interior surface defining the inter-unit channel, and the biological subject flows through these multiple inter-unit channels simultaneously and are sorted and separated therein. 
     
     
         20 . The apparatus of  claim 19 , wherein the first inter-unit channel is centrally positioned in the sub-equipment unit as compared to the other additional inter-unit channels and is connected to at least two other inter-unit channels; and a designed component injected into the first inter-unit channel flows from this first inter-unit channel to the other connected inter-unit channels; and wherein the designed component is optionally a bio-marker, a nano-particle, a magnetic particle, an enzyme, a protein, a light emitting component, an radio-active material, a dye, a polymer component, an organic component, a catalyst, an oxidant, a reducing agent, an ionic component, or a nano-particle attached to a bio-marker, a disturbing fluid, or a combination thereof. 
     
     
         21 . The apparatus of  claim 3 , wherein the sub-equipment unit further comprises a probing unit which is capable of applying a probing signal to the biological subject or a media in which the biological subject is contained, thereby changing the nature or value of a property of the biological subject or of the media; or wherein the sub-equipment unit further comprises a pre-screening unit which is capable of pre-screening a diseased biological subject from a non-diseased biological subject based on the difference in a property between a diseased biological subject and a non-diseased biological subject. 
     
     
         22 . The apparatus of  claim 1 , wherein the delivery system comprises a layer of material having an interior surface, wherein the interior surface defines an intra-unit channel in which the biological subject flows to the inter-unit channel or inter-unit channels of one or more desired sub-equipment units;
 wherein the sub-equipment unit or the sorting unit or the detection unit optionally further comprises an optical device, imaging device, camera, viewing station, acoustic detector, piezo-electrical detector, piezo-photronic detector, piezo-electro photronic detector, electro-optical detector, electro-thermal detector, electrical detector, bio-electrical detector, bio-marker detector, bio-chemical detector, chemical sensor, thermal detector, ion emission detector, photo-detector, x-ray detector, radiation material detector, electrical detector, or thermal recorder, each of which is integrated into the a panel or a micro cylinder; or   wherein the apparatus further comprises a system for distributing the biological subject, a distribution channel, a pre-processing unit, a re-charging unit, a detection device, a global positioning system, a motion device, a signal transmitter, a signal receiver, a sensor, a memory storage unit, a logic processing unit, an application specific chip, a unit for recycling and reclaiming the biological subject, a micro-electro-mechanical device, a multi-functional device, or a micro-instrument to perform surgery, drug delivery, cleaning, or medical function.   
     
     
         23 . The apparatus of  claim 1 , further comprising a central control unit that is connected to each sub-equipment unit, and capable of controlling the biological subject to be transported to and detected by one or more desired sub-equipment units, and reading and analyzing the detected data from each sub-equipment unit,
 wherein the central control unit further comprises a controlling circuitry, an addressing unit, an amplifier circuitry, a logic processing circuitry, an analog device, a memory unit, an application specific chip, a signal transmitter, a signal receiver, or a sensor; the central control unit optionally comprises a pre-amplifier, a lock-in amplifier, an electrical meter, a thermal meter, a switching matrix, a system bus, a nonvolatile storage device, or a random access memory; and the sensor optionally comprises a thermal sensor, a flow meter, an optical sensor, an acoustic detector, a current meter, an electrical sensor, a pH meter, a hardness measurement sensor, an imaging device, a camera, a piezo-electrical sensor, a piezo-photronic sensor, a piezo-electro photronic sensor, an electro-optical sensor, an electro-thermal sensor, a bio-electrical sensor, a bio-marker sensor, a bio-chemical sensor, a chemical sensor, an ion emission sensor, a photo-detector, an x-ray sensor, a radiation material sensor, an electrical sensor, a magnetic sensor, an electro-magnetic sensor, a voltage meter, a thermal sensor, a flow meter, or a piezo-meter.   
     
     
         24 . The apparatus of  claim 2 , wherein the layer of that defines the inter-unit or intra-unit channel comprises a biocompatible material on its interior surface; and the biocompatible material is optionally a synthetic polymeric material, phosphate based material, carbone based material, carbone oxide based material, carbone oxynitride based material, or naturally occurring biological material. 
     
     
         25 . The apparatus of  claim 1 , wherein the disease is a cancer, optionally selected from the group consisting of breast cancer, lung cancer, esophageal cancer, intestine cancer, cancer related to blood, liver cancer, stomach cancer, cervical cancer, ovarian cancer, rectum cancer, and circulating tumor cells. 
     
     
         26 . A method for detecting a disease in a biological subject, comprising contacting the diseased biological subject with a detection apparatus which comprises:
 a first sub-equipment unit for detecting a property of the biological subject;   at least one additional sub-equipment unit for detecting the same or different property of the biological subject as the first sub-equipment unit;   a delivery system comprises at least one intra-unit channels for transporting the biological subject to one or more desired sub-equipment units;   optionally, a central control system that is connected to each sub-equipment unit and the delivery system, and capable of controlling the biological subject matter to be transported to one or more desired sub-equipment units and reading, analyzing or displaying the detected property of the biological subject from each sub-equipment unit;   optionally, a reclaiming or treatment system that is connected to each sub-equipment unit for reclaiming or treatment medical waste from each sub-equipment unit;   
       wherein each sub-equipment unit optionally comprises an inter-unit channel, a sorting unit, a detection unit, a probing unit, or a pre-screening unit; and the sub-equipment units, the delivery system, the central control system when present, and the reclaiming or treatment system when present are all combined and integrated in the detection apparatus;
 and processing the data on the detected property of the biological subject by the first sub-equipment unit and the additional sub-equipment unit to obtain information about the disease to be detected. 
 
     
     
         27 . The method of  claim 26 , wherein the diseased biological subject is cells, a sample of an organ or tissue, DNA, RNA, virus, or protein. 
     
     
         28 . The method of  claim 27 , wherein the cells are circulating tumor cells or cancer cells, wherein the cancer is optionally selected from the group consisting of breast cancer, lung cancer, esophageal cancer, intestine cancer, cancer related to blood, liver cancer, stomach cancer, cervical cancer, and ovarian cancer. 
     
     
         29 . The method of  claim 28 , wherein each property to be detected by a sub-equipment unit or a detection unit or a sorting unit is independently a thermal, optical, acoustical, biological, chemical, physical-chemical, electro-mechanical, electro-chemical, electro-chemical-mechanical, bio-physical, bio-chemical, bio-mechanical, bio-electrical, bio-physical-chemical, bio-electro-physical, bio-electro-mechanical, bio-electro-chemical, bio-chemical-mechanical, bio-electro-physical-chemical, bio-electro-physical-mechanical, bio-electro-chemical-mechanical, physical, an electric, magnetic, electro-magnetic, or mechanical property of the biologic subject or cells contained therein.