Comprehensive Health Status by Simultaneously Reading Volatile and non-Volatile Compounds

Abstract

The present invention provides an improved system, device, and method for determining a comprehensive state of health in real time using non-invasive patient testing. The invention characterizes disease and other states of health by simultaneously assaying both liquid and gas in a sample or samples. During metabolism, the body performs a large variety of biochemical reactions. Reaction products, reaction by-products, and breakdown products are transported by the circulatory system throughout the body. Many of these molecular products are labile and volatilize into gases from bodily liquids. In gas form, these compounds appear as volatile organic compounds (VOCs).

Claims

1. An array of sensor elements (SEs) comprising a plurality of adjustably controlled sensor elements whose sensitivities and/or specificities are differentiated and addressed based on the physical position of each sensor in the array, wherein sensor elements disposed for earlier contact with molecules of a sample control delivery of compounds to be sensed by sensors disposed for subsequent contact with said molecules.

2. The array of claim 1 wherein elements disposed for earlier contact with molecules of a sample contact said molecules suspended or dissolved in a liquid.

3. The array of claim 1 wherein said elements disposed for earlier contact adjustably maintain proximity to a group of molecules with a specificity relatively less specific than sensor elements physically disposed for later contact.

5. The array of claim 2 wherein said elements disposed for earlier contact adjustably maintain proximity to a group of molecules with a specificity relatively less specific than sensor elements physically disposed for later contact.

6. The array of claim 3 wherein said elements disposed for earlier contact are at a temperature less than sensor elements physically disposed for later contact.

7. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample maintain a preferred proximal association with molecules, on average, heavier than molecules less preferred and more rapid in passing through this part of the array.

8. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample are capable of temperature modulation to release from proximal association molecules that on average are lighter than molecules whose proximal association is maintained.

9. The array of claim 2 wherein sensor elements disposed for earlier contact with molecules of a sample are in a zone capable of temperature modulation to release from liquid molecules that on average are lighter than molecules whose solubility is greater.

10. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample maintain proximal association with molecules, on average, larger in physical dimension than molecules more rapidly passing through to the later encountered parts in the array.

11. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample are capable of temperature modulation to release from proximal association molecules that on average are smaller in physical size than molecules whose proximal association is maintained.

12. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample maintain proximal association with molecules, on average, more polar than molecules more rapid in passing through the array.

13. The array of claim 2 wherein sensor elements disposed for earlier contact with molecules of a sample maintain greater fractional amounts of molecules, on average, more polar than molecules released to a gas phase.

14. The array of claim 1 wherein sensor elements disposed for earlier contact with molecules of a sample are capable of charge modulation to release from proximal association molecules that on average are less polar than molecules whose proximal association is maintained.

15. The array of claim 1 wherein said array of sensor elements is fashioned in a pattern with crossing strands forming interconnecting intersections.

16. The array of claim 2 wherein said array of sensor elements is fashioned in a pattern with crossing strands forming interconnecting intersections.

17. The array of claim 15 comprising a plurality of layers having said pattern with crossing strands forming interconnecting intersections.

18. The array of claim 16 comprising a plurality of layers having said pattern with crossing strands forming interconnecting intersections.

19. The array of claim 17 wherein said plurality of layers is stacked at an angle approximately 90° with respect to the pattern with crossing strands forming interconnecting intersections.

20. The array of claim 18 wherein said plurality of layers is stacked at an angle approximately 90° with respect to the pattern with crossing strands forming interconnecting intersections.

21. The array of claim 15 wherein said intersections comprise communication nodes permitting cross strands to modulate sensing parameters of cross strands.

22. The array of claim 16 wherein said intersections comprise communication nodes permitting cross strands to modulate sensing parameters of cross strands.

23. The array of claim 21 wherein said communication nodes participate in a circuit that modulates sensing parameters of a set of sensor elements neighbor to a first sensor element.

24. The array of claim 23 wherein said circuit is preprogrammed to modulate said parameters of said set of sensor elements by changing a sensing parameter selected from the group consisting of: voltage, temperature and frequency of alternating charge.

25. The array of claim 23 said circuit is programmed to change a sensing parameter selected from the group consisting of: voltage, temperature and frequency of alternating charge based on a signal from said first sensor element.

26. The array of claim 25 wherein said program incorporates a machine learned component.

27. The array of claim 26 wherein said machine learned component physically tracks a sensed molecule as said sensed molecule transfers from a first sensor element to a second sensor element.

28. The array of claim 1 wherein sensors disposed for subsequent contact with said molecules contact said molecules in a gas state.

29. The array of claim 28 wherein said liquid off gasses said molecules into said gas state.

30. The array of claim 21 wherein a semipermeable membrane, permeable to vapor phase, but impermeable to the liquid phase serves as a barrier between said to phases.

31. The array of claim 1 interfaced with a preprocessing sample feeder device.

32. The array of claim 31 wherein said preprocessing sample feeder device comprises a mass spectrometry device.

33. The array of claim 31 wherein said preprocessing sample feeder device comprises a chromatographic device selected from the group consisting of a gas chromatographic device and a liquid chromatographic device.

34. The array of claim 1 wherein said sensor elements comprise a sensing compound selected 25 from the group consisting of: synthetic polymers, metallic oxides, single walled carbon nanotube (SWNT), graphene and hybrids thereof.

35. The array of claim 1 comprising a port for delivering a gas sample.

36. The array of claim 2 comprising a port for delivering a liquid sample.

37. The array of claim 1 comprising a plurality of modules wherein at least two modules are connected by a vapor permeable passage.

38. The array of claim 2 wherein said elements disposed for earlier contact with molecules of a sample contact suspended or dissolved in a liquid is connected by a vapor permeable passage to sensors disposed for subsequent contact with said molecules.

39. The array of claim 37 wherein at least one of said modules comprises at least one SE comprising graphene.

40. The array of claim 39 wherein said at least one SE comprising graphene is disposed for contacting said sample suspended or dissolved in a liquid.

41. The array of claim 38 wherein said graphene comprises a shape selected from the group consisting of: flat, crumpled, rolled and folded.

42. The array of claim 40 wherein said graphene comprises a shape selected from the group consisting of: flat, crumpled, rolled and folded.

43. The array of claim 39 wherein at least one of said modules comprises at least one SE comprising a single walled carbon nanotube.

44. The array of claim 1 in communication with a data processing computer.

45. The array of claim 29 where said off gassing is controlled by a temperature increase in said liquid.

Description

BRIEF DESCRIPTION OF THE PRESENT INVENTION

[0021] Miniaturization of sensor elements has continued to drive further applications in fields of environmental safety, medical diagnostics, weather, natural and anthropomorphic contributions to localized and global climate change, as well as many other specialized interests. One such strategy for using micro-devices has been to rely on an interaction between a chemically adsorbent or interactive layer and electrical induction. Specificity of the sensor, i.e., the ability to differentiate a large number of distinct or related molecular types is required for broad-based applicability of sensing devices that are suitable for use across a variety of applications, for example, diagnosing specific diseases and developmental stages in single cell organisms, plants, animals, humans, etc.

[0022] Single walled carbon nanotubules (SWNTs) and other carbon substrates such as thin or single layer graphene provide both a large surface to volume ratio to facilitate sensor—molecule interaction, and electrical conductivity that facilitate signal transduction. Zuniga, et al, described such an application using a coating of nucleic acid on a carbon surface to selectively interact with carbon containing (organic) molecules freely moving in a gaseous environment, hence the generic name, volatile organic hydrocarbons (VOCs). Nanotube sensing surfaces may be decorated with nucleic acid, e.g., DNA or RNA prepared with the natural bases or with bases in addition to the genetic coding bases. For example, one or more biopolymer, e.g., an oligonucleotide, such as single stranded DNA, may be prepared in distilled water at a convenient concentration, e.g., about 500 to 1000 μg/ml; about 600 to 900 μg/ml; about 650 to 750 μg/ml, etc. The bare nanosensor is exposed to a drop shape aliquot of decoration solution sufficient to coat the sensing element. A microliter or less is sufficient for most elements. The drop is left for a period of time to allow the decoration to diffuse and optimize alignment with multiple decorations on the element surface. A time of 30 to 60 minutes produces acceptable decorating results. An inert gas, e.g., nitrogen or argon, may be streamed to remove the water as vapor. The decorated elements are thus ready for use in analyzing VOC performance. These concentrations volumes, times, etc., are not intended to be limiting, but may be deemed appropriate for best mode disclosure.

[0023] Flushing with inert gas and/or heating can be used to cleanse the sensor arrays between assays. The data processing apparatus preferably includes rezeroing between each sample run. Cleansing can be monitored for completeness by keeping the sensors in operative mode continuously or over timed intervals during the cleanse. Quality control monitoring can signal the operator to intensify cleansing including periodic chemical assisted cleansing.

[0024] For example, an oxidizing agent can be added to the flushing gas or a liquid based cleanse can allow reorientation of the functionalizing molecules. Gas and/or liquid may be used to cleanse either or both the VOC sensor elements and the graphene based sensors. A liquid cleanse may allow freer movement of the decoration by providing an aqueous zone for diffusion and repositioning. The cleanse may include new decoration molecules in the solution. Additional molecules in the cleanse solution may provide dilute ions or polar molecules to facilitate movement and repositioning and/or replacement of the decorations. A bleaching agent may improve the cleanse. It may be delivered as a gas or in solution. For example, a halogen gas, a peroxide (e.g., H.sub.2O.sub.2), triplet oxygen, perborate (e.g., NaBO.sub.3). SO.sub.2, H.sub.2SO.sub.3, H.sub.2SO.sub.3.sup.−, SO.sub.3.sup.−2, S.sub.2O.sub.4.sup.−2, BH.sub.4.sup.−, borohydride, OCl.sup.−, Cr.sub.2O.sub.7.sup.−2, MnO.sub.4.sup.−, CH.sub.3COOH, O.sub.2.sup.−2, etc., may react with the surface molecules to move or remove molecules interfering electronic signaling. Such supercleanse may be performed periodically or as indicated by system self-diagnosis to improve sensor functioning. A cleanse may follow initial decoration and precede a second or subsequent decoration to increase sensor performance perhaps by freeing the decoration molecules to align with others for maximum stability of signal.

[0025] In the patent applications incorporated by reference above, nano-sensor elements (NSEs}, each including at least one sensing surface, are capable of, for example, of field-effect transistor (FET) or other physico-electrical property/activity. Such structures include, but are not limited to: semi-conducting nano-wires, carbon nano-tubes—including single-wall carbon nano-tubes, chitosan-cantilever based, synthetic polymers—including dendrimers, plasmon resonance nano-sensors, Förster resonance energy transfer nano-sensors, paramagnetic compounds, surface active crystals, vibrational phonon nano-sensors, magnetically resonant compositions, optical emitting or transforming compositions, optical frequency (or wavelength) based nano-sensors (sensitive to photon transmittance, absorption, reflection, energy modulation, etc.).

[0026] Nano FETs and other nano-sensor formats generally operate by changing electrical properties as a substance comes in close proximity to the sensor. The interaction between electrons of the sensed molecule and the sensor surface perturbs the steady state of that surface to elicit its signal. The altered distribution of electrons induced by a proximal molecules, (depending on the design of the nano-sensor) changes one or more electrical properties, e.g., impedance, resistance-conductivity, capacitance, inductance, etc., and thus the physical movement of a detectable particle, e.g., an electron, a photon, etc.

[0027] The present invention features improvements based on one or more of these concepts. The invention provides a complex interacting structure allowing improved differentiation, sensitivity and specificity for detection a large variety of VOCs in the gas phase and larger molecules that tend to remain in the liquid fraction. As VOCs and solvent are vaporized from the liquid fraction, the concentrations of the larger, non-volatile or less volatile biomolecules increases. The partitioning of VOCs between phases as concentrations change may be one variable used for characterizing of identifying a VOC. As larger molecules become more concentrated, intermolecular attractions will increase as the ability of solvent to separate them lessens. Complexes formed between receptive molecules will interact with the sensors in manners distinct from the parts that form the complex. These newly formed compositions provide additional relevant responses for signature definition.

[0028] Sensors are disposed in a multi-layered stack of sensor arrays in a three-dimensional configuration with the sensor elements controllable in real-time for adjusting the sensing parameters of any activated sensor and its near neighbors. In the liquid environment, each sensor array is porous in two dimensions to the solvent, usually water. In stacked arrays in the liquid phase biomolecules are mobile between layers. Similarly, in the gaseous environments, the vapor molecules are free to move in three dimensions. A barrier impermeable to liquid, but freely permeable to vapors, may be installed to distinguish the liquid and gas sensing zones. Such impermeable barrier is especially useful in low or zero gravity environments and also allows for configurations where the liquid phase is not necessarily below the gaseous phase.

[0029] This three-dimensional format featuring controlled movements of sensed molecules can be applied to distinguish a currently sensed molecule from other molecules that may appear similar on that one sensor. The actively sensing element may continue to maintain close or tight proximity to the molecule with signal strength changing as the sensor parameters change and/or neighbor sensors may be engaged to fine tune the identification of that molecule. It is well understood and recognized that certain tuned parameters will decrease rather than increase interaction with the subject molecule and that this decreased interaction will aid in molecular characterization and identification of the subject molecule.

[0030] Preferably the stacked sensor elements are distributed across and through sequential layers of a mesh form, e.g., like a woven fabric, sponge-like, or porous formation. Solid strands forming the 3-D mesh pattern may be configured as crossing strands, e.g., at 90° to cross links or may include multiple crossing patterns such as 60° angles. The crossing fibers may contribute to a three-dimensional network. While each direction of mesh fiber may support sensor elements along its length, sensor strands may alternate side by side or be disposed in only a subset of directional strands. Sensors may be sited at fiber intersections and/or between intersections. A class of strands may lack sensors, for example, only providing structure and/or controlling circuitry. A strand may sport identical sensors along its length or may present sensors differentially decorated. Sensors may be individually controlled or in some configurations or sequences, a plurality of sensors may be sited as a pod acting in close proximity or unison. Sensors in pods may be controlled individually or, for example, may share a controlled T. Different decorations on individual sensors can competitively attract vapor molecules. V, V change frequency, or other controlled parameter may be applied as attraction differentiating tools independent of identical or different decorations.

[0031] Strands of the fabric may include a core of synthetic polymer (including biopolymer), semi-conducting or metallic like conducting strands, carbon fibers, etc. At a base surface in the stack, the fibers preferably include constant or variable electrical resistance to allow controlled heating (i.e., controlled T) of the entire layer or portion thereof. Convective, electromagnetic or other heating functions may be used at the designers and/or operators discretion. Cross fibers in the weave may be used to control T or in preferred embodiments to control the heating of specific sensor elements. Strands may have different diameters in different layers. Within a layer, stands in one orientation may differ in composition and or thickness from strands in another orientation. A strand may have zones of thinner or thicker diameter or shape. Strands are not necessarily round, but may be any suitable shape, including but not limited to flat, triangular, ellipsoid, etc. Carbon fiber, including single waled nanotubes, are optionally used. Sensors may comprise circuitry without attached sensors. Sensor strands may incorporate embedded circuitry. Layers or strands may communicate wirelessly or though one-, two- or three-dimensional circuitry.

[0032] Patterns other than cross-threaded fabric patterns are also possible. For example, a pattern featuring concentric rings, circular or concentric closed patterns of a plurality of linear segments. Rays traversing or connecting inner to outer rings serve as supporting structure and are available for circuitry carrying signals from sensors and/or instructions for modulating sensor characteristics. Such stacked concentric patterns may have a cylindrical shape each layer approximating the diameter of its neighbor(s). A tapered or conical shape may be preferred in some applications.

[0033] In especially preferred embodiments impedance is one factor that is controlled as a means of metering or reversing electron flow to control T and sensor base V. NSEs may be any micro or nano sensor element reactive to proximal molecules, whose attraction and proximity is under control of a factor including, but not limited to: base V, fluctuating resonant fields, T, carrier gas, interaction(s) with identical/similar or dissimilar ambient VOCs, photo-activation and/or excitement, sonic stimulation, etc. For example, photo-excitation may serve to dampen or increase sensor attraction to a species of molecular isomer, especially when polarized light is used and the affected molecules are chiral. The fluctuation of tautomeric ratios with different attractions to a sensor element can serve as an important distinguishing feature for identifying the molecule. Electric pulsation and especially high-frequency impedance may serve to control a molecule's movement. One or more portions of the sensing device may monitor impedance change resulting from proximity of a VOC or other gaseous species.

[0034] A high density stacking or high-count weave is preferred so that the sensing surfaces interacting zones predominate over non-interacting gas or liquid volume (free space). Limited free space between sensor elements decreases the volume of gas and available distance of a compound from a sensor element and increases availability for proximity interactions. By minimizing dead zones (volumes where molecules are unlikely to interact with a sensor element) readability is improved. The weave however must still permit the flow of the bulk gas or liquid so that compounds of interest have mobility between the available layers. An interlayer distance, when greater than the interweave may permit two-dimensional control between the layers. A fiber to pore ratio between approximately 95:1 and 5:1 is featured in preferred embodiments. Thus ratios of about: 90:1, 85:1, 80:1, 78:1, 75:1, 70:1, 67:1, 60:1: 50:1, 40:1, 33:1, 30:1, 25:1, 20:1, 17:1, 15:1, 12:1, 10:1, 7.5:1, 5:1, and intermediary ratios may be used in select embodiments. In general, but not a requirement, the fiber to pore ratio will be lower in liquid sensing modules since viscosity of the carrier liquid will almost always exceed that of the gaseous environment in the “upper” module. The interlayer distance is often set larger than the pore area to provide improved feasibility for managing flows parallel to the sensor layers.

[0035] Embodiments may feature sensors dispersed in a suspension. In this format, the sensor elements would be at the local ambient T that may be zonally controlled, for example using light, container wall or protrusion T, sonic heating, etc. Sensors interacting with a targeted compound would signal, in at least one manner including but not limited to: emitting light, changing absorbance or reflectivity, fluorescing, precipitating, adhering to a container component, changing shape, etc. Such module may be used on conjunction with the liquid and/or gaseous module(s), or to assay a small number of known compounds or classes of compounds.

[0036] While each layer is selectively configured with a desired pore-volume ratio, subsequent layers may be similarly configured possibly operating under at least one different controlling factor for proximity binding. For example, cooler temperature in a base layer may be applied as a reservoir or filter to monitor and/or manage timed release of compounds for analysis by subsequent layers. A higher base V, positive or negative, may predominate in introductory layers with subsequent layers expressing reduced V. Time, as an adjunct or alternative to physical location, is another means of managing sensor parameter gradients. For example, a time dimension may be used wherein over a preprogrammed or algorithmically determined (e.g., sensor signal dependent) process, T is raised to provide T dependent partial pressure and kinetic energy increase as potential distinguishing factors useful for compound characterization and differentiation.

[0037] In some embodiments, the baser layers can be configured to act at higher Ts, selectively reactive to less volatile components. As the mixture migrates through the stack, T, V or another binding controlling factor, is modulated to increase attraction.

[0038] Preferred embodiments feature assaying the identical sample in both liquid and gaseous phase. The sample is introduced into a liquid phase sensing module. The liquid phase module is preferably outfitted with sensor elements exhibiting sensing and reporting capabilities not available in the gaseous environment. Larger, non-volatile or lesser volatile compounds are advantageously detected and quantified in this liquid environment. Proteins, protein fragments, peptides, membrane fragments, virions, bacteria, ions, phospholipids, fatty acids, cytokines, interferons, prostaglandins, vitamins, etc., which might be impossible or difficult to assay using the gas phase sensor are thus assayable simultaneously with VOCs obtained (off-gassed) from the same sample in a single device in a single analytical run. Samples may be pre- or post- processed, e.g., one or more processes including, but filtration, centrifugation chromatography, mass spectrometry, dilution, dialyzing, heating, etc., when desired by the user.

[0039] Embodiments may feature different sensor types or classes in the liquid and gaseous module. Each module may include a variety of sensor types. Some examples may feature interacting surfaces including, but not limited to: synthetic polymers, metallic oxides, SWCN, graphene and hybrids thereof, etc., to attractively accomplish and maintain proximity of compounds of analytical interest. Graphene is one example of carbon substrate whose surface can be associated with functional or “decorative” molecules that can be designed or randomly selected for specificity and/or quantitation of compounds of interest. When the decoration may be uncharacterized, e.g., a result from interaction with a mixture of compounds e.g., random nucleic acids, fragments of larger molecules, the algorithms recognize the interactions of each sensor without regard to the decoration. The algorithms have no requirement that any decoration be defined, just how the sensor attracts and interacts with the encountered components. However, any relevant information, including, e.g., decoration binding, may contribute to characterizing or confirming the identity or class of interacting compounds. Rutile crystalline structure semiconducting strands may participate in sensing and/or circuitry.

[0040] Graphene sensors may be configured as flat, i.e., essentially planar, save for the bend introduced by the chemical bond angles or may be processed to exhibit a thicker, more three-dimensional structure, for example, a folded, rolled or crumpled graphene. Graphene surfaces may exhibit increased porosity by including gaps or perforations, i.e., discontinuous non-sensor layer portions interspersed within a continuous mesh of structural and/or sensing capable material. Such gaps or perforations may be regularly sized and spaced or may be pseudo-randomly distributed during synthesis. Within a module, layers may incorporate different formats such as synthetic polymer, SWNT, etc. A plurality of liquid and/or gas phase modules may be present or selectively used in some embodiments.

[0041] A woven structure featuring sensing elements coated on or around supportive fiber threads 30 allows the supporting matrix to be designed to feature a local information processing function. For example, a sensor indicating near proximity of VOC (or other molecule, e.g., a fatty acid in the liquid module) may initiate a local processing function to alter traits of neighbor sensors. These neighbors may be programmed with altered parameters including, but not limited to: base V, frequency, T, etc., to better characterize or to better attract the molecule at interest. Such processing may be used to track the compound throughout the array providing multi-dimensional binding characteristic information on the electronically monitored compound. Noting the different affinities under different sensing conditions provides valuable information not obtainable in devices without these capabilities. For some applications a module, layer, channel within a module, 2- or 3-dimensional zone may not be activated for the entire assay or a time portion of the assay. The operator will select component portions to address the desired data.

[0042] In a simple example, a liquid phase module is disposed at the base of the device. Gravity maintains the liquid in contact with the, e.g., graphene sensor layer(s) and separate from an over-lying gas, aka, “headspace”. The headspace may be small, e.g., a minimum separation between the phases, or may be larger with a cross-section that permits sample processing between the liquid and gas phases. However, the headspace may feature active processing components. For example, molecules driven from the liquid phase module may be addressed with electromagnetic radiation, sonic radiation, electric fields and/or magnetic fields to chemically or physically change or fix characteristics. For example, tuning, e.g., a sonic wave system may be employed to resonantly lengthen or unfold a molecule. In select circumstance, the processed molecule may be reintroduced to the liquid phase module having had a different set of atoms now exposed to sensor elements. An electric field may be applied to guide movement of charged particles. When gravity is not the force maintaining lamellar arrangement of the phases, centrifugal action may be applied to drive denser molecules towards the periphery.

[0043] In routine operations the liquid phase module may be heated, using bulk and/or targeted energy delivery systems. For example, microwave stimulation may be used to excite aqueous samples to higher kinetic status and thereby drive off volatile compounds as the affinity for water is overcome by their kinetic energy. Sonic influences, vibration, resistance heating, etc., the solvent in the liquid sensing module. Available forces for controlling movements of compounds are known in the art. For example, forces including, but not limited to: electric, magnetic, electromagnetic, acoustic, photo-excitation or photon momentum, etc., may be selected depending on particular circumstance.

[0044] Where interest in VOCs predominates and in circumstances where liquid phase analysis is not desired, a gaseous sample may be delivered directly into a gas analysis module or may be delivered through an “empty” liquid module. This allows the NSEs sited in the liquid to interact with vapor molecules. The operator may select this present option whenever, said operator desires such additional analysis.

[0045] In environments where a liquid may be unwanted. E.g., where Ts are below the solvent freezing point, the solvent may be corrosive or otherwise damaging, or other operator encountered reason, the device may effect analysis of VOCs “sublimed” out of a solid sample. At the operator's choice, the VOCs may be analyzed using liquid module sensor elements, gas module sensor elements or both.

[0046] The present invention may incorporate conventional sample acquisition and preparation processes. For example: urine may be collected from self-voiding into a container, catheterization when necessary or desired, a diaper or other absorbent material, etc.; sweat may be obtained collecting droplets or using absorbents; other liquids may be obtained by available means such as swabbing, spitting, etc. Gaseous samples may be collected as off gasses from a liquid sample or vaporizations off the targeted body area, part or zone.

[0047] Preprocessing of samples using components or processes including but not limited to: filters, aerosolizing, centrifugation, chromatography, tagging, mass spectrometry, solvent extraction, dialysis, salting, etc., may be applied in some embodiments. Postprocessing to fragment, separate, and/or refine identification is also anticipated in some embodiments.

[0048] As an example, not intended to limit scope of the invention, a urine or blood sample may be filtered or centrifuged to exclude solids which may be separately analyzed. A liquid phase and/or its off-gasses may be fed directly into the device as described above. However, preprocessing as in this example, may be a refining tool. The liquid may be processed through a gas or liquid chromatograph. Dialysis may be used to restrict size of the molecules of interest. GC-MS is a conventional separation and analysis technique that may be enhanced using nanosensor arrays as described herein. Such conventional analyses may be used in series or in parallel with the liquid and or gas phase nanosensor array analysis. For example, GC-MS may be used to confirm findings or to differentiate molecules that may have been detected but not conclusively identified passing through the detector modules.

[0049] These multistage analytical procedures can increase specificity, selectivity, quantification and other results obtainable for a sparser repertoire of sensor decorations, such as the nucleic acid functionalities popular in the art.