NL2020538B1

NL2020538B1 - Method and apparatus for connecting human biological information and data to the cloud

Info

Publication number: NL2020538B1
Application number: NL2020538A
Authority: NL
Inventors: Adelzadeh Farokh; Shachar Yehoshua
Original assignee: Sensor Kinesis Corp
Priority date: 2018-03-06
Filing date: 2018-03-06
Publication date: 2019-09-13

Abstract

The illustrated embodiments include a method of communicating human biological information to a digital cloud comprising the steps of: disposing a biological sample into a biological assay 5 device; processing the biological sample in the biological assay device to detect human biological data; communicating the human biological data to a cloud-based database; providing the human biological data to a cloud-based database to a plurality of users communicating With the cloud-based database; and further processing or using the human biological data by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose.

Description

FIELD OF THE INVENTION

The invention relates to the field of digital computing or data processing equipment, systems or methods specifically adapted for biological information.

INTRODUCTION

It is believed by many that the developed world economies are currently in a stage of technological innovation that advances and impacts lives like never seen before, namely a Fourth Industrial Revolution. The fuel that burns, propels and accelerates this Fourth Industrial Revolution and pushes it forward faster and faster is the rapid rate of change in disruptive technologies. All aspects of life are impacted by these innovations and disruptive technologies. Among these tidal waves of disruptive technologies that move this massive revolution are artificial intelligence (Al), the internet of things (loT), autonomous vehicles, robotics, DNA sequencing, and quantum computing, just to mention a few.

Humanity and nature are inherently biological. There are forty-six human chromosomes containing six billion bits of information. The planet’s population is approximately seven billion and growing. Current technological advances will not currently suffice to fully include the biological realm in the Fourth Industrial Revolution. What is needed is a direct link between the biology of a human and the digital domain on a scale that allows voluminous amounts of data and information from human biology to be processed at digital speeds. What is needed is a means to link biology to the digital domain, which means is the last remaining missing piece in omniconnectivity, namely connecting humanity’s biological information and data via the cloud to billions of smart devices.

The digitization of the output of clinical diagnostic instruments and upload of that information to the Cloud or computer networks is well known, but involves the possession and operation of diagnostic equipment and performance of diagnostic methods well beyond any possible use in the field or any possible use by the patient him or herself or for that matter most field health workers. Further, the diagnostic test and the logistical limitations of transporting the biological sample to the clinical laboratory introducing transport of distances requiring time, not including the diagnostic time which may be many hours to days or weeks. Medical diagnostic testing is simply not in the hands of the nonskilled end user any more than computing was in the hands of the nonskilled user of the computational results before the invention of the personal computer.

What is needed is an apparatus and methodology wherein the patient, as the end user of a medical diagnostic test, is effectively provided personal access and control to diagnostic medical testing and its immediately utilization or communication to medical physicians for utilization in a diagnosis and therapy.

The disclosed embodiments are directed to what is a generation of profound technological innovation that advances and impacts lives like in a Fourth Industrial Revolution.

The embodiments generally employ the concept of creating a biochemical event or signal that is diagnostically indicative of some property or parameter of interest. The biochemical signal is then detected or converted into an analog electrical signal that can be processed to provide a quantified measure of the biochemical signal. The analog electrical metrical signal is thus amenable to analog data processing. All possible mathematical manipulations can be applied in the analog domain to the analog electrical metrical signal to derive any desired measure of the detected biochemical signal or event. Thereafter or even without analog data processing, the electrical signal can be digitized, data processed in digital form and/or communicated to a proximate or remote data utilization device or user.

By making the creation of an analog biochemical event or signal and its detection into an analog electrical signal in a field deployable device capable of automatic operation without operator intervention, by making the detection of clinical diagnostic quality or significance, and by performing it within a practical time period of the order of 15 minutes or less with a low limit of detection, medical diagnostic testing is effectively placed in the hands of the enduser of the diagnostic test results, the patient himself, who then can readily communicate the results to the medically expert community for effective diagnosis and treatment. For the first time, the individual human biology of any and every person readily becomes internet accessible.

The illustrated embodiments include a method of communicating human biological information to a digital cloud comprising the steps of: disposing a biological sample into a biological assay device; processing the biological sample in the biological assay device to detect human biological data; communicating the human biological data to a cloud-based database; providing the human biological data from the cloud-based database to a plurality of users communicating with the cloud-based database; and further processing the human biological data such that it is suitable for use by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose.

The method may also comprise using the human biological data by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in a handheld device.

The step of processing the biological sample in a handheld device may comprise processing the biological sample in a handheld device without the need for a trained operator.

The step of communicating the human biological data to a cloud- based database may comprise communicating the human biological data from a handheld network connected device.

The step of communicating the human biological data from a handheld network connected device may comprise communicating the human biological data from a handheld internet connected device.

The step of communicating the human biological data from a handheld network connected device may comprise communicating the human biological data from a handheld satellite connected device.

The step of disposing a biological sample into a biological assay device may comprise disposing blood, bodily fluids of any kind, stool samples, cell or tissue samples, breath samples, skin scrapings, hair samples, or fingernail samples.

The step of processing the biological sample in a handheld device without the need for a trained operator may comprise the use of a field portable, handheld, recirculating surface acoustic wave analyzer.

The method may further comprise the step of storing the detected human biological data in the biological assay device for at least a predetermined temporal period.

The step of communicating the human biological data to a cloud- based database may comprise communicating the human biological data to a cloud- based database after the predetermined temporal period.

The step of disposing a biological sample into a biological assay device, processing the biological sample in the biological assay device to detect human biological data, communicating the human biological data to a cloud- based database, and providing the human biological data from the cloud-based database to a plurality of users communicating with the cloud-based database may comprises repeating the steps of disposing, processing, communicating and providing for an identified portion of a human population by action of the members of the identified portion of a human population, so that biological information with respect to the identified portion is digitally and preferably omniconnected to the cloud subject to confidential control by each member of the identified portion of human population.

This embodiment of the method may further comprise using the biological information from the cloud-based database to develop diagnostic expertise through artificial intelligence from biological information relating to the entire identified portion of the human population or a substantial subset of the identified portion of the human population. Alternately or additionally, this embodiment of the method may further comprise using the biological information from the cloud-based database to establish or detect epidemiological trends, data and/or predictions

The method may further comprise the step of processing biological information from the cloudbased database such that it is suitable for use in providing medical treatment of the individual subject from who the biological sample originated. The method may also comprise using the biological information from the cloud-based database to provide medical treatment to the individual subject from who the biological sample originated, for instance to provide medical treatment of an individual subject living in a third-world environment using developed world diagnostic or therapeutic resources.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in the biological assay device to detect human biological data in a field portable, handheld, recirculating surface acoustic wave analyzer.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in the biological assay device to detect human medical markers or data, disease or cancer biomarkers, genetics, RNA, DNA, bacteria, viruses, fungi, health data, metabolic or health biomarkers, or genetic barcode tags.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in the biological assay device to detect human biological data in an impedimetric detection device.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in the biological assay device to detect human biological data using a bioFET sensor.

The step of processing the biological sample in the biological assay device to detect human biological data may comprise processing the biological sample in the biological assay device to detect human biological data using a carbon nanotube bioFET device.

The step of processing the biological sample in the biological assay device to detect human biological data using a carbon nanotube bioFET device may comprise using a carbon nanotube bioFET with a local amplifier in a system array for analysis of biomarkers.

The illustrated embodiments also extend to a method of communicating information to a digital cloud comprising the steps of: disposing a sample into an assay device; processing the sample in the assay device to detect a predetermined type of data; communicating the predetermined type of data to a cloud-based database; providing the predetermined type of data from the cloud-based database to a plurality of users communicating with the cloud-based database; and further processing or using the predetermined type of data by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose, explosives detection for terrorism defense, environmental sensing of toxins, pollutants or other atmospheric components, or general epidemiological information.

While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims are not to be construed as necessarily limited in any way by the construction of “means” or “steps” limitations, but are to be accorded the full scope of the meaning and equivalents. The disclosure can be better visualized by turning now to the following drawings wherein like elements are referenced by like numerals.

Brief Description of the Drawings

Fig. 1 is a diagram illustrating the field portable analysis device in communication with the cloud to provide digital biological data concerning a human subject to a database accessible to a worldwide community of health or medical resources or users.

Fig. 2 is a system top level block diagram of microfluidic system using a SAW detector.

Fig. 3 is an orthographic cross section of an aptamer biosensor with a schematic representation of the electronic detection module.

FIG. 4 is a side cross sectional view of a diagram of the bioFET sensor with its source follower amplifier, further describing the external electrical connections and analyte representation within the volume formed out of the source-drain and gate's geometry.

The disclosure and its various embodiments can now be better understood by turning to the following detailed description of the preferred embodiments which are presented as illustrated examples of the embodiments defined in the claims. It is expressly understood that the embodiments as defined by the claims may be broader than the illustrated embodiments described below.

Detailed Description

Fig. 1 is a diagrammatic depiction of a biological assay device or system 10 into which a biological sample 12 is disposed and which is then processed. The sample 12 is shown diagrammatically as a drop of blood from the finger of a subject, but is intended to symbolize any kind of macroscopic or microscopic biological sample without limitation, e.g. blood or bodily fluids of any kind, stool samples, cell or tissue samples, breath samples, skin scrapings, hair samples, fingernail samples, etc. Furthermore, the figure should not be interpreted as implying that the claims include the step of obtaining the sample from an individual. System 10 is similarly taken to include any kind of diagnostic or assay device now known or later devised. System 10 includes without limitation large, complex immobile laboratory assay devices which require skilled operators and includes small, handheld, field mobile cell-phone sized devices, which can be operated by an unskilled layman. Of the latter is the biosensor analytic device engineering by Sensor-Kinesis Corporation of Los Angeles, California, and described in US Provisional Patent Application serial no. 62/597,202 filed on Dec. 12, 2017, and entitled Field Portable, Handheld, Recirculating Surface Acoustic Wave Analyzer and Method for Operating the Same.

SAW Detection

Turning briefly to the SAW detection system of the first embodiment, Fig. 2 is a system top level block diagram of microfluidic system 110. Microfluidic system 110 includes a disposable microfluidic cartridge 111 which is inserted into and read by a reader 113. The microfluidic cartridge 111 in turn includes a shear wave surface acoustical wave detector (SAW) 112 and a temperature sensor, micropump and mixer assembly 115. Various embodiments of SAW detector 112 known, and are for instance described in the above-mentioned U.S. Provisional Patent Application, serial no. 62/597,202, filed on Dec. 11, 2017 and entitled, “Field Portable, Handheld, Recirculating Surface Acoustic Wave and Method for Operating the Same. Reader 113 includes a signal generator 146 that is coupled to and drives SAW 12 and a signal acquisition circuit 148 coupled to SAW 12 for receiving the data signals output by SAW 112. The operation of signal generator 146 and signal acquisition circuit 148 are coupled to microcontroller 154, which proUdes signal and data processing control subject to software control. Drivers 152 are also coupled to microcontroller 154 and provide the driving and control signals to the elements of the temperature sensor, micropump and mixer assembly 115. User interface 156 is coupled to microcontroller 154 and includes output displays 158, LEDs 160, switches 162, Wi-FPBlueTooth connections 164, and secure digital (SD) card connectors 166 as described below. The circuitry of reader 113 is coupled to and powered by a power or battery source 150.

Returning to the generalized concept of Fig. 1, system 10 makes an analysis of the sample 12 and digitally communicates the output to the cloud 14, where it is stored and indexed in a biological database 16. Database 16 may similarly be provided with biological data from a multiplicity of systems 10 for a corresponding multiplicity of subjects worldwide in addition to providing biological data accessible with respect to each identified individual subject uploaded to database

16. Confidentiality and control provisions can be included in the database entries so that disclosure or use of the biological information for each subject is controllable by the subject. The subject can identify such users 18a - 18c as may be allowed to have access to the biological information and may limit the use of the information by the users 18a - 18c. Similarly, means can be provided whereby a user 18a - 18c asking for access or identified use of biological information from database 16 or a portion thereof, may have their request automatically forwarded to the user to consent, refusal or conditional limitations.

Database 16 is accessible from cloud 14 by a plurality of users 18a- 18c. Each user 18a - 18c may have a different end use or purpose for accessing database 16. For example, user 18a may be dedicated to providing medical treatment of the individual subject from who the biological sample originated. User 18b may be dedicated to developing a diagnostic expertise through artificial intelligence from the entire or a substantial portion of the database 16 subjects. User 18c may be directed to establishing and detecting epidemiological trends, data or predictions. The end use of information in database 16 has substantially no limitation, but may be directed to any conceivable aspect of human biology, health and/or medicine. Needless to say, the borders of the system of Fig. 1 are without any geographic or temporal limitation. The subject may be in Africa in a nearly inaccessible third world location having only satellite communication available with the outside world with the users 18a-18c scattered in an internet medical research network distributed throughout the developed world. The time of talcing of the sample 12 and its availability to a user 18a - 18c may be nearly immediate to being separated by years or decades of time.

In the illustrated embodiment, the democratization of human biology by interconnection to the world through cloud 14 is based on having a low cost, handheld, mobile assay system 10, such as that disclosed in the above-mentioned application entitled Field Portable, Handheld, Recirculating Surface Acoustic Wave Analyzer and Method for Operating the Same. By inclusion of a field portable, handheld device operable by untrained personnel, complex assays or detection of human biological information can be made and inserted into the digital realm of the cloud 14 for use. The human biological information which includes, but is not limited to the entire spectrum of human medical markers or data, disease or cancer biomarkers, genetics, RNA, DNA, bacteria, viruses, fungi, health data, metabolic or health biomarkers, and genetic barcode tagging and reading as developed by Brenner and Lerner in 1992. See Brenner et.al.. Proc. Natl. Acad. Sci USA 89,5381-83 (1992).

Additional Embodiments of Detection Systems

The detection mechanism in system 10 is not limited to SAW detectors as disclosed in the illustrated embodiment of Fig. 2, but includes any detection technology now known or later devised which lends itself to implementation by nonskilled health workers in the field and which is capable of making a clinical quality diagnostic test in a short period of time, such as of the order of 15 minutes with low limits of detection, ideally single analyte particle detection or detection of tens to a few hundreds of analyte particles (molecules, virus, bacteria, or nanobodies). Such additional technologies include, but are not limited to impedimetric detection, often using interdigitated electrode arrays where impedance or some measure thereof is measured; FET transistors with functionalized gates, where effectively the beta of the FET or some measure thereof is measured; three dimensional FET devices where again effectively the beta of the FET or some measure thereof is measured; functionalized liposomelysis releasing ions and/or cations where conductivity or resistivity of a buffer or some measure thereof is measured; and/or optical fluorescence detection w'here a functionalized fluorescence tag or some measure thereof is measured. Depending on the specific detection technology employed design adjustments may be required without departing from the scope of the invention to adapt or maximize the detection characteristics in combination with the fluidic circuit of Fig. 2.

For example, impedimetric detection in general, such as is conventionally known and disclosed in a wide variety of patents found in CPC classes C12Q 1/6825 ; G05B 15/02 ; C12Q 1/6827 ; GOIN 27/327 ; BOIL 3/502738 ; GOIN 27/021 ; GOIN 27/3275 ; C12Q 1/6832 ; BOIL 3/50273 ; C12Q 1/6825 ; C12Q 1/6827 ; BOIL 2300/0636 ; BOIL 2300/023 ; Y10T 436/143333 ; Y10T 436/11 ; C12Q 2527/101 ; C12Q 2527/113 ; C12Q 2565/607 and other related classes, may be used. Specific examples include, Method and Apparatus for Forming a Hemeostatic Loop Employing an Aptamer Biosensor, U.S. Pat. 8,145,434; Method and Apparatus for Detecting and Regulating Vascular Endothelial Growth Factor (VEGF) by Forming a Homeostatic Loop Employing a Half-Antibody Biosensor, U.S. Pat. Pub. 2010/0260679; Method and Apparatus for Forming of an Automated Sampling Device for the Detection of Salmonella Enterica Utilizing an Electrochemical Aptamer Biosensor, U.S. Pat. Pub. 2011/0166033 and 2011/0162979

Another example includes an aptamer-based solid-state electrochemical biosensor for labelfree detection of Salmonella enterica serovars utilizing immobilized aptamers. The device is realized by forming a matrix array of parallel capacitors similar to that shown in Fig. 3, thus allowing the realization of low-cost, portable, fully integrated devices. Protein-aptamer binding modulates the threshold voltage of a circuit, changing the impedance (capacitance) of the circuit. This circuit is further characterized by an electrode coded with a p-Si substrate, enhancing the affinity between the Salmonella outer membrane proteins (OMPs) and the aptamer. An aptamer embedded detection plate is configured within a testing lid device that fits a standard, commercially available polymer specimen jar. A sample is mixed with broth for incubation and cultivation of any present Salmonella bacteria to obtain acceptable concentration of the pathogen for testing. The information obtained can then be transmitted by wireless network.

Impedimetric Aptamer Biosensor

Fig. 3 is an orthographic cross section of the biosensor apparatus with a schematic representation of the electronic detection module. The apparatus 300 with its insulating enclosure is configured with fluid flow inlet 301, and a flow outlet 302. The electrolyte solution flows into the biosensor via the inlet 301, and out outlet 302, and possibly connected to a pump and valve arrangements. The apparatus 300 includes an array of electrodes coded with capture reagents which form the capacitive plates 303. The electrodes 303 are designed in an interdigitated fingers pattern in order to maximize the sensor surface area in a small volume. The apparatus 300 is interfaced with the electronic module 300a, which form the capacitance detector circuit. The detector circuit 300a, includes an operational amplifier buffer 301; a current-to- voltage amplifier 300c, involving a resistor 304; an op amp integration circuit 300d, involving a resistor 305, and a capacitor 306. The impedance values of the resistor 305, and capacitor 306, are matched approximately to the resistor 304, and capacitance of apparatus 300, respectively, so that the output signal 310, is approximately the same as the input square wave 307. The half period of the input square wave 307, should be significantly larger than the RC constant formed by the resistor 204, and capacitance 100, so that the op amp 302 has enough time to discharge the sharp transitions caused by the square wave 307. as the capacitance of 300 increases with arrival of target analytes, the amplitude of output signal 310, increases proportionally.

One specific example includes a biosensor for detection of vascular endothelial growth factor (VEGF) hybridization uses an array of parallel capacitors similar to that shown in Fig. 3 to detect electrochemical binding of circulating VEGF to immobilized anti-VEGF monoclonal halfantibodies (a-VEGF mhAb). Binding of a-VEGF mhAb modulates the threshold voltage of a circuit, changing the impedance of the circuit. An electrode coated with a p-Si substrate enhances the affinity between the VEGF molecules. A fluid cell delivers VEGF samples onto the active surface of the chip. An array of parallel capacitors arranged in an interdigitated pattern detects the VEGF in the fluid. The detector provides an accurately measured and quantifiable rate of change of the VEGF molecules in vivo, providing real time feedback which is used to measure response of the tumor to delivered chemotherapeutic agents and biological response modifiers (BRMs) for the purpose of determining tumor burden and efficacy of the chemotherapy as part of a homeostatic loop for chemotherapy.

BioFET Detection

Also included in particular are biosensors where the capacitance of a bioFET device provides the sensing element of the analyte, such as is conventionally known and disclosed in a wide variety of patents issued to Taiwan Semiconductor Manufacturing Company, Ltd. (Hsin-Chu, TW) and classified in CPC class GOIN 27/414 ; H01L 51/0093 ; GOIN 27/4148 ; GOIN 27/4145 ; H01L 21/84 ; H01L 27/1203 and other related classes. Similarly, detection with a carbon nanotube bioFET device is another modality of detection for handheld, field portable devices, such as disclosed a variety of patents which can be found in CPC classes GOIN 27/4145 ; GOIN 27/4146 ; H01L 51/0049 ; GOIN 33/5438 ; H01L 51/0558 and other related classes, including particularly US Patent 9,810,661, entitled Carbon Nanotube BIOFET With A Local Amplifier In A System Array For Analysis Of Biomarkers And Method Of Analysis Of Same.

Fig. 4 is a cross-section of the bioFET cell which includes: a nonconductive substrate (SiO2) 324, and/or Kapton; a gold electrode 322 acting as the source for the bioFET coupled to a high input impedance source follower amplifier 327 (e.g. source follower amplifier (SFA) acting as a buffer amplifier to provide electrical impedance matching from the bioFET 333 circuit to an analog front end computational circuit. The SFA 327 is employed as basic single-stage field effect transistor (FET) amplifier, and in this application serves as a voltage buffer. In circuit 333 the gate terminal 326 of the transistor acts as the control input, the source 322 is the current output and the drain 323 is coupled to a selected voltage source, shared between the input and output. In addition, this circuit is used to transform impedances. (Thevenin resistance of a combination of a voltage follower 327 driven by a voltage source with high Thevenin resistance is reduced to only the output resistance of the voltage follower—a small resistance). That resistance reduction makes the combination of the bioFET cell 333 and source follower 327 a more ideal voltage source. Conversely, a voltage follower inserted between a driving stage and a high current load (i.e. a low resistance) presents an infinite resistance (low current load) to the driving stage— an advantage in coupling a voltage signal to a large load, as it is typical for biosensors in this application.)

An electrode 323 acting as the drain for the bioFET cell carries the drain current. The counter electrode 317 forms part of the gate 318. The semiconductive single-walled carbon nanotubes (s-SWCNTs) 314 form the semiconductive channel between source 322 and drain 323. An electrolytic medium 328 contains various non-specific proteins 329 and the specific target biomarker 321 captured by the antibodies 320. A non-conductive layer such as SiO2 insulates the electrodes 322, 323 from the counter electrode 317 and the surface of the s-SWCNTs 314, which extends the distance 330 between the source 322 and the drain 323. The incorporation of a high impedance source follower amplifier 327 increases the signal output, hence improving signal fidelity, reducing signal-to-noise ratio, and expanded dynamic range. The use of the source follower amplifier at the local site of or situated proximately to the bioFET cell enables the simplification of the electronics by eliminating the use of an inverting amplifier and providing for a unity gain voltage buffering function, and where the voltage signal source has sufficient amplitude, but has a large internal resistance, and where the signal needs to be supplied to a load with much smaller resistance because the load on the s-SWCNT's hybridized a biological payload requires temperature control to avoid conformational changes of the protein in the payload.

To recap, the bioFET cell is a carbon nanotube based bio- impedance sensor using established field effect transistor (FET) technology. High purity, semi-conductive single walled carbon nanotubes (s-SWCNTs) 314 are used as a channel in the volumetric cell between the source and drain. The impedance of the target s-SWCNTs channel 314 is on the order of 100 kQ. The randomly oriented carbon nanotube (CNT) based semiconducting channel 314 is modified and functionalized with antibodies 320 to capture target biomarkers 321, thus transforming the device from a classic FET into a bioFET. The CNT channel 314 is a monolayer of s-SWCNTs. Source 322 and drain 323 is fabricated using silver or gold inkjet printed-electrodes. The top gate 317, i.e., the controlled electrode, is fabricated using silver or gold ink jet printed layer on the surface of the top part of the flow cell. The dimension of the control electrode 317 is defined under a guideline set by the effective sensor geometry as a volume (2 mm x 2 mm x 7 pm) of an active area of a single device to achieve a high ratio capacitive load relative to a minimum surface area while employing a boundary condition of the flow characteristic of the channel defined between the source and drain electrodes. The separation gap between the counter electrode 317 and sSWCNTs channel 314 is several hundred nanometers to a few millimeters in range, i.e., it is tunable. Distance 330 between the source and drain is 2 mm. The source and drain is covered by the nonconductive layer 326 such as epoxy (SU- 8). The aqueous solution 328 containing the analyte

321 and the buffer act as a mediator and form the dielectric of the cell prior to hybridization. It acts as the medium between the surface of s-SWCNTs layer 314 and the counter electrode 17. Consider the electrical and flow dynamic factors of the biofet design. Multiple geometrical layouts are available to realize the bioFET cell architecture and to accommodate the two fundamental principles guiding the metrics of the cell, namely the flow characteristics of the buffer and analyte. Specifically, the molecular size of the item desired to be measured such as VEGF-165 molecule ranges between 35-50 kDa, while E. coli bacteria and larger proteins measure between 200,000 kDa to 500,000 kDa. The bioFET cell is tested and evaluated in terms of transistor performance parameters. Families of I-Vds and I-Vg curves reveal essential device characteristics (DC) related to the performance of bioFET cell acting as a biosensor. These parameters include: transconductance, threshold voltage, on/off ratio, carrier mobility, etc. For the gate dependent study, a liquid gate configuration is used, where the gate voltage is actually applied through a metal path (i.e., control electrode 317) submerged in or in contact with an electrolyte solution 328. This liquid gate configuration has been demonstrated by many research groups to be an order of magnitude more effective in terms of electrical performance characteristics than conventional solid phase gating in Si/SiO2 supported gated nanotube devices. For the gate electrode 317, we employ the common Ag/AgCl electrode used in the characterization of many nanotube FET devices, as a silver chloride electrode is a commonly employed reference electrode, e.g., like the internal reference electrode in pH meters. The electrode functions as a redox electrode and the reaction is between the silver metal (Ag) and its salt-silver chloride (AgCl, also called silver (1) chloride). Applying a DC voltage (e.g., 50 mV) and a superimposed AC potential (e.g., 5 mV) between source (S) 322 and drain (D) 323, electrical current flows from the source 322 to the drain 323 through the carbon nanotube network 314. The ratio of the AC voltage to the drain AC current, measured at a specific frequency (e.g., 100 Hz), provides the impedance value of the system output. The frequency is swept as described below to show a resonance. Time dependent studies will show a saturation level.

Biological receptors such as antibodies 320 (also called capture probes or ligands) specific to target biomarkers 320 are physically bound to the surface of the nanotubes 314 via a single step linking process. When target biomarkers 321 are captured by the antibodies 320, the binding event will cause a change in the impedance. The amount of signal generated is inversely proportional to the concentration of biomarkers in the sample for a narrow range of concentrations, called the dynamic range. The curve represents the logarithmic output of the bioFET in operation. BioFET devices usually have a narrow response range. The typical S shape (reverse) of a response curve, shows the signal intensity as a function of the biomarker capturing time. At low analyte concentrations, still below the detection limit, the sensor can only display baseline signal. Once the threshold concentration is reached (limit of detection, LOD) the sensor will produce response signals linearly proportional to the concentration of the analyte which has bound (if plotted in logarithmic scale). This linear response typically spans one or two orders of magnitude of analyte concentrations. As the analyte concentration continues to increase, the sensor surface will be saturated, and the lower limit of response is reached. At the lower level, further increase in, for example, VEGF concentration as analyte, achieves saturation and generates a constant response as the capacitive load reaches its maximum coverage threshold within the geometry of the bioFET effective area.

There are many factors that influence the dynamic range of biosensors, including the binding affinity of antibodies, sensor geometry, number of active receptors on the surface, sensitivity of the transducer, etc. The bioFET sensor dynamic range is tuned to its specific application by optimizing the device geometry, as defined by the effective flow geometry as well as the distance between control electrode and the s-SWCNTs surface.

Detected or possibly detectable substances include not only biological data as contemplated in the illustrated embodiments, but also includes but is not limited to explosives detection for terrorism defense, environmental sensing of toxins, pollutants or other atmospheric components, general epidemiological information.

Many alterations and modifications may be made by those having ordinary skill in the art without departing from the scope of the embodiments. Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the embodiments as defined by the following embodiments and its various embodiments.

Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the embodiments as defined by the following claims. For example, notwithstanding the fact that the elements of a claim are set forth below in a certain combination, it must be expressly understood that the embodiments includes other combinations of fewer, more or different elements, which are disclosed in above even when not initially claimed in such combinations. A teaching that two elements are combined in a claimed combination is further to be understood as also allowing for a claimed combination in which the two elements are not combined with each other, but may be used alone or combined in other combinations. The excision of any disclosed element of the embodiments is explicitly contemplated as within the scope of the embodiments. The words used in this specification to describe the various embodiments are to be understood not only in the sense of their commonly defined meanings, but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus if an element can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself.

The definitions of the words or elements of the following claims are, therefore, defined in this specification to include not only the combination of elements which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense it is therefore contemplated that an equivalent substitution of two or more elements may be made for any one of the elements in the claims below or that a single element may be substituted for two or more elements in a claim. Although elements may be described above as acting in certain combinations and even initially claimed as such, it is to be expressly understood that one or more elements from a claimed combination can in some cases be excised from the combination and that the claimed combination may be directed to a subcombination or variation of a subcombination.

Insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, are expressly contemplated as being equivalently within the scope of the claims. Therefore, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements.

The claims are thus to be understood to include what is specifically illustrated and described above, what is conceptually equivalent, what can be obviously substituted and also what essentially incorporates the essential idea of the embodiments.

The invention is also defined by the following clauses:

1. A method of communicating human biological information to a digital cloud comprising:

disposing a biological sample into a biological assay device;

processing the biological sample in the biological assay device to detect human biological data;

communicating the human biological data to a cloud-based database; providing the human biological data from the cloud-based database to a plurality of users communicating with the cloud-based database; and further processing the human biological data such that it is suitable for use by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose.

2. The method of clause 1, further comprising using the hu- man biological data by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose.

3. The method of clause 1 or 2 wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in a handheld device.

4. The method of clause 3 where processing the biological sample in a handheld device comprises processing the biological sample in a handheld device without the need for a trained operator.

5. The method of any of clauses 1-4, wherein the communicating of the human biological data to a cloud-based database comprises communicating the human biological data from a handheld network connected device.

6. The method of clause 5 where the communicating of the human biological data from a handheld network connected device comprises communicating the human biological data from a handheld internet connected device.

7. The method of clause 5 where the communicating of the human biological data from a handheld network connected device comprises communicating the human biological data from a handheld satellite connected device.

8. The method of any of clauses 1-7 wherein the disposing of a biological sample into a biological assay device comprises disposing blood, bodily fluids of any kind, stool samples, cell or tissue samples, breath samples, skin scrapings, hair samples, or fingernail samples.

9. The method of clause 4 where the processing of the biological sample in a handheld device without the need for a trained operator comprises the use of a field portable, handheld, recirculating surface acoustic wave analyzer.

10. The method of any of clauses 1-9, further comprising storing the detected human biological data in the biological assay device for at least a predetermined temporal period.

11. The method of clause 10, wherein the communicating of the human biological data to a cloud-based database comprises communicating the human biological data to a cloud- based database after the predetermined temporal period.

12. The method of any of clauses 1-11, wherein the disposing of a biological sample into a biological assay device, the processing of the biological sample in the biological assay device to detect human biological data, the communicating of the human biological data to a cloud-based database, and the providing of the human biological data from the cloud-based database to a plurality of users communicating with the cloudbased database comprise repeating the steps of disposing, processing, communicating and providing for an identified portion of a human population by action of the members of the identified portion of a human population, so that biological information with respect to the identified portion is digitally and preferably omniconnected to the cloud subject to confidential control by each member of the identified portion of human population.

13. The method of clause 12, further comprising using the biological information from the cloud-based database to develop diagnostic expertise through artificial intelligence from biological information relating to the entire identified portion of the human population or a substantial subset of the identified portion of the human population.

14. The method of any of clauses 12-13, further comprising using the biological information from the cloud-based database to establish or detect epidemiological trends, data and/or predictions.

15. The method of any of clauses 1-14, further comprising pro- cessing the biological information from the cloud-based database such that it is suitable for use in providing medical treatment of the individual subject from who the biological sample originated.

16. The method of any of clauses 1-15, further comprising using the biological information from the cloud-based database to provide medical treatment to the individual subject from who the biological sample originated.

17. The method of clause 16, wherein the using of biological information from the cloud-based database to provide medical treatment of the individual subject from who the biological sample originated comprises using biological information from the cloud-based database to provide medical treatment of an individual subject living in a third-world environment using developed world diagnostic and/or therapeutic resources.

18. The method of any of clauses l-17,wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in the biological assay device to detect human biological data in a field portable, handheld, recirculating surface acoustic wave analyzer.

19. The method of any of clauses 1-18, wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in the biological assay device to detect human medical markers or data, disease or cancer biomarkers, genetics, RNA, DNA, bacteria, viruses, fungi, health data, metabolic or health biomarkers, or genetic barcode tags.

20. The method of any of clauses 1-19, wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in the biological assay device to detect human biological data in an impedimetric detection device.

21. The method of any of clauses 1-20, wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in the biological assay device to detect human biological data using a bioFET sensor.

22. The method of any of clauses 1-21, wherein the processing of the biological sample in the biological assay device to detect human biological data comprises processing the biological sample in the biological assay device to detect human biological data using a carbon nanotube bioFET device.

23. The method of clause 22 where the processing of the biological sample in the biological assay device to detect human biological data using a carbon nanotube bioFET device comprises using a carbon nanotube bioFET with a local amplifier in a system array for analysis of biomarkers.

24. A method of communicating information to a digital cloud comprising:

disposing a sample into an assay device; processing the sample in the assay device to detect a predetermined type of data;

communicating the predetermined type of data to a cloud-based database; providing the predetermined type of data from the cloud-based database to a plurality of users communicating with the cloud-based database; and further processing or using the predetermined type of data by at least one of the plurality of users for a biomedical informatics, diagnostic or therapeutic purpose, explosives detection for terrorism defense, environmental sensing of toxins, pollutants or other atmospheric components, or general epidemiological information.

Claims

CONCLUSIONS

A method for communicating human biological information to a digital network (the "cloud"), comprising:

supplying a biological sample to a biological analysis device;

processing the biological sample in the biological analysis device to detect human biological data;

communicating human biological data to a cloud-based database;

providing the human biological data from the cloud-based database to a plurality of users who communicate with the cloud-based database; and further processing the human biological data to be suitable for use by at least one of the plurality of users for biomedical computing, diagnostic, or therapeutic purposes.

The method of claim 1, further comprising the use of human biological data by at least one of the plurality of users for biomedical computing, diagnostic, or therapeutic purposes.

The method of claim 1 or 2, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in a portable device.

The method of claim 3, wherein processing the biological sample in a portable device comprises processing the biological sample in a portable device without the need for a trained user.

The method of any one of claims 1-4, wherein communicating the human biological data to a cloud-based database comprises communicating the human biological data from a portable network-connected device.

The method of claim 5, wherein communicating human biological data from a portable network-connected device comprises communicating human biological data from a portable Internet-connected device.

The method of claim 5, wherein communicating human biological data from a portable network-connected device comprises communicating human biological data from a portable satellite network-connected device.

A method according to any of claims 1-7, wherein supplying a biological sample to a biological analysis device comprises supplying blood, body fluids of any type, stool samples, cell or tissue samples, breath samples, skin samples, hair samples, or nail samples.

The method of claim 4, wherein processing the biological sample in a portable device without the need for a trained user involves the use of a field-portable, recirculating, surface sound wave analyzer.

The method of any one of claims 1-9, further comprising storing the detected human biological data in the biological analysis device for at least a predetermined period of time.

The method of claim 10, wherein communicating the human biological data to a cloud-based database comprises communicating the human biological data to a cloud-based database after the predetermined period of time.

The method of any one of claims 1 to 11, wherein delivering a biological sample to a biological analysis device, processing the biological sample in the biological analysis device to detect human biological data, communicating the human biological data to a cloud-based database, and providing the human biological data from the cloud-based database to a plurality of users who communicate with the cloud-based database includes repeating the steps of delivery, processing, communicating and providing for an identified portion of the human population through action of the members of the identified portion of the human population, such that biological information regarding the members of the identified portion is digitally and preferably omni-linked to the cloud, subject to confidential co control by each member of the identified portion of the human population.

The method of claim 12, further comprising using biological information from the cloud-based database for developing diagnostic expertise, via artificial intelligence, based on biological information related to the entire identified portion of the human population or a significant subset of the identified portion of the human population.

The method of any one of claims 12-13, further comprising using the biological information from the cloud-based database to determine or detect epidemiological trends, data and / or predictions.

The method of any one of claims 1-14, further comprising processing the biological information from the cloud-based database such that it is suitable for use in providing medical treatment for the individual whose biological sample comes from.

The method of any one of claims 1-15, further comprising using the biological information from the cloud-based database to provide medical treatment for the individual from whom the biological sample originates.

The method of claim 16, wherein using the biological information from the cloud-based database to provide medical treatment of the individual from whom the biological sample originates comprises using biological information from the cloud based database to provide medical treatment of an individual person living in a third-world environment using diagnostic and / or therapeutic resources from the developed world.

The method of any one of claims 1-17, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in the biological analysis device to detect human biological data detect in a field portable, recirculating, surface sound wave analyzer.

The method of any one of claims 1-18, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in the biological analysis device for human medical markers or data to detect disease or cancer biomarkers, genetics, RNA, DNA, bacteria, viruses, fungi, health data, metabolic or health biomarkers, or genetic barcode tags.

The method of any one of claims 1-19, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in the biological analysis device to detect human biological data in an impedimetric detection device.

The method of any one of claims 1-20, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in the biological analysis device to detect human biological data using a bioFET sensor.

The method of any one of claims 1-21, wherein processing the biological sample in the biological analysis device to detect human biological data comprises processing the biological sample in the biological analysis device to detect human biological data using a carbon nanotube bioFET device.

The method of claim 22, wherein processing the biological sample in the biological analysis device to detect human biological data using a carbon nanotube bioFET device comprises using a carbon nanotube bioFET with a local enhancer in a system array for analyzing biomarkers.

A method for communicating information to a digital network (cloud), comprising:

delivering a sample to a device for analysis;

processing the sample in the analyzer for a predetermined type

5 detect data;

communicating the predetermined type of data to a cloud-based database;

providing the predetermined type of data from the cloud-based database to a plurality of users who communicate with the cloud-based database; and further processing or using the predetermined type of data by at least one of the plurality of users for biomedical informatics, diagnostic or therapeutic purposes, explosive detection for defense against terrorism, measuring toxins, pollution or other atmospheric components in the environment, or general epidemiological information.

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