Systems and methods employing nanomaterial sensors for detecting conditions impacting a Volatile Organic Compounds (VOCs) profile in breath
Sensors
Systems and methods employing nanomaterial sensors for detecting conditions impacting a Volatile Organic Compounds (VOCs) profile in breath (TOP2-328)
E-Nose: a rapid, low-cost handheld test device utilizing nanomaterial sensors for analyte sensing
Overview
NASA Ames had previously developed a nanosensor array that uses a sample of patient breath for medical diagnosis. (See TOP2-169.) However, the specific materials that can be used had not been previously identified. NASA Ames has made further developments to enhance the capabilities of the technology to detect a variety of Volatile Organic Compounds (VOCs). A highly sensitive sensor array featuring 64 chemically sensitive nanomaterials can accurately identify various health and biological conditions, such as detection of Covid-19 in humans. The technology can also provide a non-invasive approach for sensing biological conditions in dairy and animal husbandry. 64 distinct sensing nanomaterials, including nanotubes, composite nanotubes, nanoparticle-decorated (doped) nanotubes, and polymer-coated nanotubes, having the greatest sensitivity to VOCs in concentrations as low as 2 to 5 ppb have been identified, and exemplary formulations for each identified nanomaterial have been developed.
The Technology
The technology involves a sophisticated system designed to detect conditions through the analysis of exhaled breath, utilizing an array of nanomaterial sensors fabricated upon a standard printed circuit board with interdigitated electrodes. These sensors are configured to interact with a sample gas that contains various Volatile Organic Compounds (VOCs) associated with a variety of biological conditions. Each sensor consists of nanomaterials, such as carbon nanotubes, composite nanotubes, nanoparticle-doped nanotubes, or polymer-coated nanotubes, all disposed on an electrically conductive structure. These sensors are highly sensitive to specific VOCs at a broad spectrum of concentrations, and each sensor generates a unique measurable electrical signal on interaction with VOCs in the breath that reflects the presence and concentration of specific components in the sample gas. The previously nanosensor diagnosis technology has been further developed to identify 64 specific formulations of nanomaterials that exhibit unique and varying sensitivities to VOCs, which enables unique response signatures to be developed for a wide range of VOCs. A single device may be developed using these principles to detect a variety of health conditions and diseases.
Benefits
- Levels of detection (LODs) in the parts per billion (ppb) range; detection levels as low as 2-5 ppb are feasible.
- User-friendly, Low power consumption, small size, and high discrimination power
- Operates at room temperature
- Cost efficient and can be easily manufactured using standard materials processing methods
- Miniaturization, and real time operation can be integrated with a smart phone and other hand-held devices for the application of breath diagnosis
- Able to sense a large variety of VOCs for purposes of determining the presence or absence of a given condition.
- The sensor array provides “cross sensitivity,” which can improve selectivity toward identification of the signature and mitigate false positives
- The enhancement in sensitivity can be achieved without compromising the selectivity and reversibility (i.e., reusability) of the sensor
- High number of binding sites increases analyte adsorption per unit area, thereby improving detection sensitivity for one or more analytes
- High surface area per unit volume of the nanomaterials, allows effective adsorption, even of weakly interacting substances, and produces a detectable response, all while maintaining a compact profile
Applications
- Heath care industry - clinical applicability where conditions are detectable in breath • COVID-19 Screening • Diabetes • Detection of other disease/human health conditions
- Medical diagnosis
- Disease prevention
- Therapeutic monitoring
- Food safety (spoilage), food quality assessment
- Animal and livestock health
- Astronaut health in spaceflight
- Air Quality monitoring
- Agricultural research
- Forensic science
Technology Details
Sensors
TOP2-328
ARC-18952-1
ARC-16902-1
https://pubs.acs.org/doi/10.1021/acssensors.3c00367?ref=pdf
ARC-16902-1 https://technology.nasa.gov/patent/TOP2-169.
Similar Results
Nanosensor Array for Medical Diagnoses
Many diseases are accompanied by characteristic odors. Their recognition can provide diagnostic clues, guide the laboratory evaluation, and affect the choice of immediate therapy. The study of the chemical composition of human breath using gas chromatography mass spectrometry (GC/MS) has shown a correlation between the volatile compounds and the occurrence of certain illnesses. The presence of those specific compounds can provide an indication of physiological malfunction and support the diagnosis of diseases. This condition requires an analytical tool with very high sensitivity for its measurement. A number of volatile compounds, so called biomarkers, are found in breath samples, normally at low parts per billion (ppb) levels. For example, the acetone in the exhaled breath from human with other biomarkers can indicate Type I diabetes. Usually, the concentration of the volatile compounds in human breath is very low and the background relative humidity is high, almost 100%. NASAs invention utilizes an array of chemical sensors combined with humidity, temperature, and pressure for real-time breath measurement to correlate the chemical information in the breath with the state and functioning of different human organs. This tool provides a non-invasive method for fast and accurate diagnosis at the medical point of care or at home. The sensor chip includes multisensors for a comprehensive measurement of chemical composition, temperature, humidity, and pressure/flow rate. The sensor data collected from this chip can be wired or wirelessly transmitted to a computer terminal at the doctors desk or hospital monitoring center. The sensor chip can be connected directly or via Universal serial bus (USB) to a cell phone for data transmission over a long distance and receive an instruction from a doctors office for an immediate therapy.
Hybrid carbon nanotube-gold nanoparticle composite for Nitric Oxide (NO) detection
A hybrid thin film is fabricated by a simple drop-casting method. Functionalized single-walled carbon nanotubes (SWCNTs) and gold nanoparticles (AuNPs) with a diameter of ≈15 nm are drop-casted onto a printed circuit board (PCB) substrate equipped with interdigitated electrodes. The addition of AuNPs to the carbon nanotube networked films enhance sensitivity and lower the detection limit to low parts-per-billion (ppb) concentrations. The gold particle to carbon nanotube ratio is optimized to find the optimum gold nanoparticle loading.
The composite films were tested in both air and nitrogen environments across a wide relative humidity range (0-97%), which is suitable for dissolved Nitric Oxide (NO) detection in sea water for oceanographic study and for human breath analysis in medical diagnosis. The sensors exhibited high selectivity, particularly to NO, outperforming other tested gases. Notably, the sensor reliably detected NO at 10 ppb levels with response times within 10 seconds and recovery time around 1 minute, showcasing excellent reproducibility across sensors and operational efficiency within diverse humidity conditions.
Electrochemical Sensors Based on Enzyme-Linked Immunosorbent Assay
NASA’s electrochemical Enzyme-Linked Immunosorbent Assay (ELISA) microelectrode array biosensor advantageously incorporates a microbead detection construct, coupled with a magnetic immobilization construct, which substantially increases the signal sensitivity of a sensor. The magnetic immobilization construct draws the microbead detection construct to an electrode detection surface, enhancing signal sensitivity. By concentrating the signaling molecules close to the electrode detection surface, electrochemical redox cycling is achieved by reducing the distance between the two, allowing for regeneration of reporter molecules.
Whereas a traditional ELISA testing exhibits five to ten signaling molecules per probe molecule binding event, the present electrochemical ELISA-based biosensor testing exhibits up to 4,857 signaling molecules per probe molecule binding event. The model bead construct exhibits a more than 6.75-fold in increased measured signal, and more than 35.7-fold improvement in signal sensitivity. When compared to traditional optical ELISA, the present invention improves the limit of detection by up to a factor of 60.5.
NASA’s electromagnetic ELISA-based biosensor can be used for the detection of SARS-CoV-2 virus to enhance Covid-19 testing during the early phases of infection. The technology may also be modified to detect other biomarkers.
Gas Sensors Based on Coated and Doped Carbon Nanotubes
A typical sensor device includes a set of interdigitated microelectrodes fabricated by photolithography on silicon wafer or an electrically insulating substrate. In preparation for fabricating the SWCNT portion of such a sensor, a batch of treated (coated or doped) SWCNTs is dispersed in a solvent. The resulting suspension of SWCNTs is drop-deposited or injected onto the area containing the interdigitated electrodes. As the solvent evaporates, the SWCNTs form a mesh that connects the electrodes. The density of the SWCNTs in the mesh can be changed by varying the concentration of SWCNTs in the suspension and/or the amount of suspension dropped on the electrode area. To enable acquisition of measurements for comparison and to gain orthogonality in the sensor array, undoped SWCNTs can be similarly formed on another, identical set of interdigitated electrodes. Coating materials tested so far include chlorosulfonated polyethylene. Dopants that have been tested include Pd, Pt, Au, Cu and Rh nanoparticle clusters. To date, the sensor has been tested for NO2, NH3, CH4, Cl2, HCl, toluene, benzene, acetone, formaldehyde and nitrotoulene.
Portable Medical Diagnosis Instrument
The technology utilizes four cutting-edge sensor technologies to enable minimally- or non-invasive analysis of various biological samples, including saliva, breath, and blood. The combination of technologies and sample pathways have unique advantages that collectively provides a powerful analytical capability. The four key technology components include the following: (1) the carbon nanotube (CNT) array designed for the detection of volatile molecules in exhaled breath; (2) a breath condenser surface to isolate nonvolatile breath compounds in exhaled breath; (3) the miniaturized differential mobility spectrometer (DMS) -like device for the detection of volatile and non-volatile molecules in condensed breath and saliva; and (4) the miniaturized circular disk (CD)-based centrifugal microfluidics device that can detect analytes in any liquid sample as well as perform blood cell counts. As an integrated system, the device has two ports for sample entry a mouthpiece for sampling of breath and a port for CD insertion. The breath analysis pathway consists of a CNT array followed by a condenser surface separating liquid and gas phase breath. The exhaled breath condensate is then analyzed via a DMS-like device and the separated gas breath can be analyzed by both CNT sensor array again and by DMS detectors.
