APPARATUS FOR DETECTING TUMOR CELLS
Among others, the present invention provides apparatus for detecting circulating tumor cells, comprising a system delivery biological subject and a probing and detecting device, wherein the probing and detecting device includes a first micro-device and a first substrate supporting the first micro-device, the first micro-device contacts a biologic material to be detected and is capable of measuring at the microscopic level 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 property, or a combination thereof, of the biologic subject.
1 . An apparatus for detecting tumor cells in a biological subject, comprising a system for delivering the biological subject and a probing and detecting device.
2 . The apparatus of claim 1 , wherein the probing and detecting device is capable of detecting, counting and recording the number of tumor cells in a biological subject.
3 . The apparatus of claim 2 , wherein the probing and detecting device is further capable of marking the cancer progression of a biological subject by the amount of tumor cells detected.
4 . The apparatus of claim 1 , wherein the tumor cells in the biological subject are circulating tumor cells.
5 . The apparatus of claim 1 , wherein the probing and detecting device comprises a first micro-device and a first substrate supporting the first micro-device, the first micro-device contacts the biologic subject to be detected and is capable of measuring at the microscopic level an electric, magnetic, electro-magnetic, 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, or mechanical property of the biologic subject or cells contained therein.
6 . The apparatus of claim 5 , wherein the difference in the measured property between the detected biologic subject and a standard biologic sample, or between cells contained in the detected biological subject and normal cells, is indicative of the possible existence of circulating tumor cells.
7 . The apparatus of claim 5 , wherein 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 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 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.
8 . The apparatus of claim 5 , wherein the probing and detecting device applies to the biological entity a voltage ranging from about 0.1 mV to about 10 V or from about 1 mV to about 1.0 V.
9 . (canceled)
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11 . The apparatus of claim 5 , wherein the first micro-device has a size ranging from about 1 angstrom to about 5 millimeter.
12 . The apparatus of claim 5 , wherein the probing and detecting device further comprises one or more additional micro-devices, each of which is also capable of measuring at the microscopic level 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 property, or a combination thereof, of the biologic subject.
13 . The apparatus of claim 12 , wherein each of the first and additional micro-devices comprises a conductive material, an electrically insulating material, a biological material, or a semiconductor material.
14 . The apparatus of claim 13 , wherein each of the additional micro-devices comprises a material that is the same as or different from the material of the first micro-device and is capable of measuring the same or different property of the biologic material as the first-micro-device.
15 . The apparatus of claim 12 , wherein the first micro-device and each of the additional micro-devices are capable of measuring 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; temperature or vibrational frequency; optical absorption, optical transmission, optical reflection, optical-electrical property, brightness, or fluorescent emission; radiation property is radiation emission, signal triggered by radioactive material, or information probed by radioactive material; 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; density, shape, volume, or surface area; 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; frequency, speed of acoustic waves, acoustic frequency and intensity spectrum distribution, acoustic intensity, acoustical absorption, or acoustical resonance; internal pressure, hardness, flow rate, viscosity, fluid mechanical properties, shear strength, elongation strength, fracture stress, adhesion, mechanical resonance frequency, elasticity, plasticity, or compressibility.
16 . (canceled)
17 . The apparatus of claim 14 , wherein each of the additional micro-devices has a size ranging from about 1 angstrom to about 5 millimeter.
18 . The apparatus of claim 12 , wherein the micro-devices are spaced out on the substrate by a distance of at least 10 angstroms.
19 . The apparatus of claim 18 , wherein the distance between two adjacent micro-devices ranges from about 5 microns to about 100 microns.
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22 . The apparatus of claim 5 , wherein the probing and detecting device further comprises a second substrate of the same or different material as the first substrate.
23 . The apparatus of claim 5 , further comprising a device for reading the data from measuring the property by the probing and detecting device.
24 . The apparatus of claim 4 , further comprising a fluid delivering system which comprises a pressure generator, a pressure regulator, a throttle valve, a pressure gauge, and distributing kits.
25 . The apparatus of claim 24 , wherein the pressure generator comprises a motor piston system and a bin containing compressed gas.
26 . (canceled)
27 . (canceled)
28 . The apparatus of claim 24 , wherein the fluid to be delivered is liquid.
29 . The apparatus of claim 28 , wherein the liquid is a blood sample, an urine sample, a saliva sample, a tear sample, a sweat sample, or a lymph sample.
30 . The apparatus of claim 5 , wherein the probing and detecting device further comprises a system controller which comprises a pre-amplifier, a lock-in amplifier, an electrical meter, a thermal meter, a switching matrix, a system bus, a nonvolatile storage device, a random access memory, a data processing unit, a logic unit, a processor, or a user interface.
31 . The apparatus of claim 30 , wherein the interface comprises a sensor.
32 . The apparatus of claim 31 , wherein the sensor comprises a thermal sensor, a flow meter, an optical sensor, a voltage meter, a current meter, an electrical sensor, a pH meter, a hardness measurement sensor, a thermal sensor, a flow meter, or a piezo meter.
33 . The apparatus of claim 4 , further comprising a biological interface, a system controller, a system for reclaiming or treatment medical waste.
34 . The apparatus of claim 33 , wherein reclaiming and treatment of medical waste is performed by the same system or different systems.
35 . (canceled)
36 . The apparatus of claim 4 , further comprising a system for delivering the biological subject, 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.
37 . The apparatus of claim 36 , wherein the pre-processing unit comprises a filtration unit, a nutrient and respiring gas recharging unit, a constant pressure delivery unit, or a sample disturbing unit.
38 . The apparatus of claim 4 , wherein the system for delivering the biological subject comprises at least one channel inside which the biological subject travels in a certain direction; the probing and detecting device comprises at least one probing micro-device and at least one detecting micro-device, at least one probing micro-device is located before at least one detecting micro-device relative to the direction in which the biological subject travels, and the probing micro-device and the detecting micro-device can be attached to the interior or exterior wall of the channel.
39 . The apparatus of claim 38 , wherein the probing and detecting device comprises at least two detecting micro-devices capable of measuring at the microscopic level the same or different properties of the biological subject.
40 . The apparatus of claim 39 , wherein the detecting micro-devices are capable of measuring at the microscopic level 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; temperature or vibrational frequency; 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; 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; density, shape, volume, or surface area; 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; frequency, speed of acoustic waves, acoustic frequency and intensity spectrum distribution, acoustic intensity, acoustical absorption, or acoustical resonance; internal pressure, hardness, flow rate, viscosity, fluid mechanical properties, shear strength, elongation strength, fracture stress, adhesion, mechanical resonance frequency, elasticity, plasticity, or compressibility.
41 . The apparatus of claim 38 , wherein the shapes and sizes of different sections of the channel can be the same or different.
42 . The apparatus of claim 38 , wherein the width of the channel ranges from about 1 nm to about 1 mm.
43 . (canceled)
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45 . The apparatus of claim 44 , wherein the interior wall of the channel defines a circular, oval, polygon, or rectangular space.
46 . The apparatus of claim 45 , wherein the channel s a circular carbon nano-tube.
47 . The apparatus of claim 46 , wherein the carbon nano-tube has a diameter from about 0.5 nm to about 1 micron and a length from about 5.0 nm to about 10 mm.
48 . The apparatus of claim 38 , wherein the interior wall of the channel has at least one concave that may be in the same section as a probing or detecting micro-device.
49 . (canceled)
50 . The apparatus of claim 48 , wherein the concave groove is a depth of from about 10 nm to about 1 mm.
51 . The apparatus of claim 38 , wherein a disturbing fluid is injected into the channel, either before or after the biological subject passes a probing micro-device, to aid the traveling or separation of the biological subject inside the channel.
52 . The apparatus of claim 51 , wherein the distribution fluid is injected into the channel through a distribution fluid channel connected to an opening in the channel wall.
53 . The apparatus of claim 38 , wherein the apparatus is for detecting circulating tumor cells in two or more biological subjects, and the channel comprises a device located therein for separating or dividing the biological subjects based on different levels of a same property of the biological subjects.
54 . The apparatus of claim 53 , wherein the separating or dividing device is a slit and separates or divides biological subjects based on their surface charges.
55 . The apparatus of claim 38 , further comprising a filtering device for removing irrelevant objects from the biologic subject for detection.
56 . The apparatus of claim 4 , further comprising a unit for delivering the biological subject, a channel, a pre-processing unit, a re-charging unit, a detection unit, a data storage unit, a data analysis unit, a central control unit, a biological sample recirculation unit, a waste disposal unit, a global positioning system, a motion device, a signal transmitter, a signal receiver, a sensor, a logic processing unit, an application specific chip, a micro-electro-mechanical device, a multifunctional device, or a micro-instrument to perform surgery, drug delivery, cleaning, or medical function.
57 . The apparatus of claim 56 , wherein the apparatus is integrated on a single device or a board.
58 . The apparatus of claim 56 , wherein the pre-processing unit comprises a filtration unit, a nutrient and respiring gas recharging unit, a constant pressure delivery unit, or a sample disturbing unit.
59 . The apparatus of claim 1 , wherein the tumor cells are from prostate cancer, lung cancer, colon cancer, breast cancer, brain cancer, cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, leukemia, liver cancer, ovarian cancer, skin cancer, testicular cancer, thyroid cancer, pancreatic cancer, endometrial cancer, esophageal cancer, or uterine cancer.
60 . An apparatus for interacting with a biological subject to detect circulating tumor cells therein, comprising one device for sending a signal to the biological subject and optionally receiving a response to the signal from the biological entity.
61 . The apparatus of claim 60 , wherein the interaction with the biological subject is probing, detecting, analyzing, sorting, communicating with, treating, correcting, or modifying with 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 property, or a combination thereof, of the biologic subject.
62 . The apparatus of claim 60 , wherein the device comprises multiple surfaces coated with one or more elements or combinations of elements, and a control system for releasing the elements.
63 . (canceled)
64 . (canceled)
65 . The apparatus of claim 60 , wherein the device comprises a first component for storing or releasing one element or a combination of elements onto the surface of the cell or into the cell; and a second component for controlling the release of the elements.
66 . The apparatus of claim 65 , wherein the second unit is a circuitry for controlling the release of the elements.
67 . The apparatus of claim 65 , wherein the element is a biological component, a chemical compound, ions, catalysts, a bio-chemical component, Ca, C, Cl, Co, Cu, H, I, Fe, Mg, Mn, N, O, P, F, K, Na, S, Zn, or a combination thereof.
68 . The apparatus of claim 60 , wherein the signal is in the form of a released element or combination of elements.
69 . The apparatus of claim 68 , wherein the signal is carried in a liquid solution, gas, or a combination thereof.
70 . (canceled)
71 . The apparatus of claim 60 , wherein the signal is at a frequency ranging from about 1×10 −4 Hz to about 100 MHz.
72 . The apparatus of claim 60 , wherein the signal comprises the oscillation of a biological component, a chemical compound, ions, catalysts, a bio-chemical component, Ca, C, Cl. Co, Cu, H, I, Fe, Mg, Mn, N, O, P, F, K, Na, S, Zn, or a combination thereof.
73 . The apparatus of claim 72 , wherein the signal comprises the oscillation of Ca, C, Cl, Co, Cu, H, I, Fe, Mg, Mn, N, O, P, F, K, Na, S, Zn, or a combination thereof at an oscillation frequency ranging from about 1×10 −4 Hz to about 100 Hz.
74 . The apparatus of claim 72 , wherein the signal comprises the oscillation of Ca, C, Cl, Co, Cu, H, I, Fe, Mg, Mn, N, O, P, F, K, Na, S, Zn, or a combination thereof at an oscillation concentration ranging from about 1.0 nmol/L to about 10.0 mmol/L.
75 . The apparatus of claim 60 , wherein the response from the biological entity comprises 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 property, or a combination thereof.
76 . The apparatus of claim 60 , wherein the response from the biological entity comprises a chemical compound, a biological component, an element, ions, catalysts, or a combination thereof.
77 . The apparatus of claim 60 , wherein the response from the biological entity is at oscillating frequencies.
78 . The apparatus of claim 60 , wherein the device is coated with a biologically compatible film.
79 . The apparatus of claim 60 , wherein the device comprises components for generating a signal to be sent to the biological entity, receiving a response to the signal from the biological entity, analyzing the response, processing the response, interfacing between the device and the biological entity, communicating with the biological entity, modifying certain aspects of the biological entity, or correcting certain aspects of the biological entity.
80 . The apparatus of claim 60 , wherein the signal to be sent to the biological entity is in the form of oscillating element, compound, chemical compound, ions, catalysts, bio-chemical component, or biological component density outside or inside cell membrane, and a response to the signal from the cell is in the form of oscillating element, a compound, ions, catalysts, or a biological component density outside or inside cell membrane.
81 . The apparatus of claim 60 , wherein the device comprises a probe and the probe is able to move the biological subject.
82 . The apparatus of claim 81 , wherein the probe comprises a flexible supporting structure to extend or contract the probe to move the biological subject.
83 . The apparatus of claim 60 , wherein the device comprises a probe and the probe is connected to the controlling circuit.
84 . The apparatus of claim 60 , wherein the biological subject is a blood sample, a lymphocyte sample, a bone marrow sample, a urine sample, a saliva sample, a tear sample, a sweat sample, a lymph sample, or a treated solution thereof.
85 . The apparatus of claim 60 , further comprising a unit for delivering the biological subject, a channel, a pre-processing unit, a re-charging unit, a detection unit, a data storage unit, a data analysis unit, a central control unit, a biological sample recirculation unit, a waste disposal unit, a global positioning system, a motion device, a signal transmitter, a signal receiver; a sensor, a logic processing unit, an application specific chip, a micro-electro-mechanical device, a multifunctional device, or a micro-instrument to perform surgery, drug delivery, cleaning, or medical function.
86 . The apparatus of claim 85 , wherein the pre-processing unit comprises a filtration unit, a nutrient and respiring gas recharging unit, a constant pressure delivery unit, or a sample disturbing unit.
87 . (canceled)
88 . The apparatus of claim 60 , wherein the tumor cells are from prostate cancer, lung cancer, colon cancer, breast cancer, brain cancer, cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, leukemia, liver cancer, ovarian cancer, skin cancer, testicular cancer, thyroid cancer, pancreatic cancer, endometrial cancer, esophageal cancer, or uterine cancer.
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122 . An apparatus for detecting circulating tumor cells in a biological subject, comprising a pre-processing unit, a re-charging unit, a probing and detecting unit, a signal processing unit, and a disposal processing unit.
123 . The apparatus of claim 122 , wherein the pre-processing unit comprises a sample filtration unit, a nutrient and respiring gas recharging unit, a constant pressure delivery unit, or a sample pre-probing disturbing unit.
124 . The apparatus of claim 123 , wherein the sample filtration unit comprises an entrance channel, a disturbing fluid channel, an accelerating chamber, and a slit.
125 . The apparatus of claim 124 , wherein a bio-compatible fluid is injected into the disturbing fluid channel to separate the biological subject.
126 . The apparatus of claim 125 , wherein the bio-compatible fluid is injected from the entrance of the disturbing fluid channel and delivered to an opening in the entrance channel wall.
127 . The apparatus of claim 125 , wherein the bio-compatible fluid comprises saline, water, oxygen rich liquid, an intravenous solution, or plasma.
128 . The apparatus of claim 124 , wherein the angle between the entrance channel and the disturbing fluid channel ranges from about 0° to about 180°, from about 30° to about 150°, from about 60° to about 120°, or from about 75° to about 105°, or about 90°.
129 . The apparatus of claim 124 , wherein the width of each channel ranges from about 1 nm to about 1 mm.
130 . The apparatus of claim 124 , at least one of the channels comprises one probing device attached to the channel's sidewall, wherein the probing device is capable of measuring at the microscopic level 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 property, or a combination thereof, of the biologic subject.
131 . The apparatus of claim 123 , wherein the sample filtration unit comprises an entrance channel, a biocompatible micro-filter, or an exit channel.
132 . The apparatus of claim 131 , wherein the biocompatible micro-filter is capable of filtering the biological subject based on at least one property selected from physical size, hardness, elasticity, shear strength, weight, surface features, dynamic surface features, optical, acoustical, thermal, fluid properties, properties due to interactions between biological entity and micro-filter, dynamic response due to interactions between biological entity and micro-filter, chemical, mechanical, electrical, biological, physical-chemical, bio-physical, bio-chemical, electro-chemical, magnetic, electro-magnetic, electro-mechanical, electro-chemical-mechanical, bio-chemical-mechanical, bio-physical-chemical, bio-electro-chemical, and bio-electro-chemical-mechanical property.
133 . The apparatus of claim 133 , wherein 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 thermal property is temperature or vibrational frequency; the optical property is optical absorption, optical transmission, optical reflection, optical-electrical property, brightness, or fluorescent emission; 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 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.
134 . The apparatus of claim 130 , wherein at least one of the channels comprises at least two probing devices attached to the channel's sidewalls, and each of the probing devices are capable of measuring at the microscopic level an electric, magnetic, electro-magnetic, thermal, optical, acoustical, biological, chemical, physical-chemical, electro-mechanical, electro-chemical, electro-chemical-mechanical, bio-physical, bio-chemical, bio-mechanical, bio-electro-mechanical, bio-electro-chemical, bio-physical-chemical, bio-electro-chemical-mechanical, physical or mechanical property of the biological subject.
135 . (canceled)
136 . The apparatus of claim 134 , wherein 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 thermal property is temperature or vibrational frequency; the optical property is optical absorption, optical transmission, optical reflection, optical-electrical property, brightness, or fluorescent emission; 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 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.
137 . (canceled)
138 . The apparatus of claim 123 , wherein the sample pre-probing disturbing unit comprises one micro-device with a channel, a pair of plates, and a slit located in the channel to separate the channel into a top channel and a bottom channel.
139 . The apparatus of claim 138 , wherein the sample pre-probing disturbing unit applies to the biological entity 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 property, or a combination thereof.
140 . (canceled)
141 . The apparatus of claim 122 , wherein the re-charging unit re-charges nutrient or respiring gas or respiring fluid to the biological subject.
142 . The apparatus of claim 141 , wherein the nutrient comprises bio-compatible strong or weak electrolyte, amino acid, mineral, ions, oxygen, oxygen-rich liquid, intravenous solution, glucose, or protein; respiring fluid comprises oxygen rich liquids; and the respiring gas comprises oxygen.
143 . The apparatus of claim 122 , wherein the signal processing unit comprises an amplifier, a lock-in amplifier, an A/D converter, a micro-computer, a manipulator, a display, or network connections.
144 . The apparatus of claim 143 , wherein the signal processing unit collects more than one signals, and the signals can be integrated to cancel noise or to enhance the signal to noise ratio.
145 . The apparatus of claim 122 , wherein the biological subject comprises blood, urine, saliva, tear, sweat, or lymph.
146 . The apparatus of claim 122 , wherein the tumor cells are from prostate cancer, lung cancer, colon cancer, breast cancer, brain cancer, cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, leukemia, liver cancer, ovarian cancer, skin cancer, testicular cancer, thyroid cancer, pancreatic cancer, endometrial cancer, esophageal cancer, or uterine cancer.