Biomarker Sensor Arrays for Microfluidics Applications

The innovative technology from Ames acts as a microfluidics switch array, using combinations of pressure and flow conditions to achieve specific logic states that determine the sequences of sample movement between microfluidic wells. This advancement will enable automation of complex laboratory techniques not possible with earlier microfluidics technologies that are designed to follow predetermined flow paths and well targets. This novel method also enables autonomous operations including changing the flow paths and targeting well configurations in situ based on measured data decision parameters. This microfluidic system can be reconfigured for use in various experimental applications, requiring only an adjustment of the programmed pressure sequencing, reducing the need for custom design and development for each new application. For example, this technology could provide the ability to selectively constrain or move biological specimens in the experimental wells, allowing evolutionary studies of model organisms in response to various stressors, evaluation of different growth conditions on biological production of antibodies or other small molecule therapeutics, among other potential applications. Likewise, this platform can be used to foster time-dependent, step-wise, chemical reactions, which could be used for novel chemical processes or in situ resource utilization.

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.

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.

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.

The SansEC sensor is an open circuit without electrical connections, which functions as an electrical simple harmonic oscillator when exposed to a harmonic magnetic field. Its response is dependent upon the measured physical property. It consists of a uniquely designed thin-film electrically conductive geometric pattern that stores energy in both electric and magnetic fields. When wirelessly interrogated using the NASA developed Magnetic Field Response Recorder (U.S. Patent Number 7,159,774), the sensor becomes electrically active, and a chemical reactant works in tandem with the thin-film trace. If the chemical is present, it causes a change to the reactant, resulting in an alteration to the sensors magnetic field response attributes. This change is noted electronically by the Magnetic Field Response Recorder.