In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.

Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aß), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aß, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aß, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.

Functionalized-Graphene Field Effect Transistor-Based Biosensor for Ultrasensitive and Label-Free Detection of ß-Galactosidase Produced by Escherichia coli.

The detection of ß-galactosidase (ß-gal) activity produced by Escherichia coli (E. coli) can quickly analyze the pollution degree of seawater bodies in bathing and fishing grounds to avoid large-scale outbreaks of water pollution. Here, a functionalized biosensor based on graphene-based field effect transistor (GFET) modified with heat-denatured casein was developed for the ultrasensitive and label-free detection of the ß-gal produced by E. coli in real water samples. The heat-denatured casein coated on the graphene surface, as a probe linker and blocker, plays an important role in fabricating GEFT biosensor. The GFET biosensor response to the ß-gal produced by E. coli has a wide concentration dynamic range spanning nine orders of magnitude, in a concentration range of 1 fg·mL-1-100 ng·mL-1, with a limit of detection (LOD) 0.187 fg·mL-1 (1.61 aM). In addition to its attomole sensitivity, the GFET biosensor selectively recognized the ß-gal in the water sample and showed good selectivity. Importantly, the detection process of the ß-gal produced by E. coli can be completed by a straightforward one-step specific immune recognition reaction. These results demonstrated the usefulness of the approach, meeting environmental monitoring requirements for future use.

A novel biosensor based on a bio-barcode for the detection of Mycobacterium tuberculosis.

Tuberculosis (TB), the second (after COVID-19) deadliest infectious killer, is a chronic infectious disease caused by infection with Mycobacterium tuberculosis (M.T.), where early diagnosis and management are the key to containing the condition. Here, we report a novel biosensor for the detection of M.T. DNA based on magnetic separation, urease catalysis and silicon nanowire field effect transistor (SiNW FET) detection. M.T. DNA is sequence-specifically captured by magnetic nanoparticles and urease-labelled silica nanoparticles simultaneously to form a sandwich complex and urea is catalyzed into ammonium carbonate by urease modified on a sandwich complex. By using SiNW FET, the detection of M.T. DNA is realized indirectly by the detection of ammonium carbonate. The limit of detection (LOD) was determined to be 78.541 fM. The specificity of the biosensor was confirmed by detecting a panel of bacterial species. The utility of the biosensor was demonstrated in real-sample analysis and the recovery study of M.T. DNA was done in the genomic DNA extracted from cultured Mycobacterium tuberculosis. The biosensor holds promise to become a rapid, sensitive and accurate method for clinical diagnosis.

Rapid and quantitative detection of tear MMP-9 for dry eye patients using a novel silicon nanowire-based biosensor.

Dry eye disease (DED) is the most common chronic eye disease characterized by ocular surface inflammation that affects hundreds of millions of people worldwide. The diagnosis and monitoring of DED require fast and reliable tools in the clinical setting. Matrix metalloproteinase 9 (MMP-9) has been proven to be a reliable indicator of DED owing to its close relationship with inflammation. A novel biosensor based on silicon nanowire-based field-effect transistor (SiNW FET) devices was fabricated for the quantitative measurement of MMP-9 in human tears. A modified controllable process was applied to improve the uniformity of the SiNWs in size and stabilize their performance with optical calibration at low salt concentrations for clinical application. With this protocol, correlation analysis proved the high agreement between the biosensor and enzyme-linked immunosorbent assay (correlation coefficient of 0.92 for DED patients and 0.90 for healthy controls). A diagnostic sensitivity of 86.96% and specificity of 90% were achieved in human tear samples from DED patients and healthy subjects in real-world clinical settings. Furthermore, the tear MMP-9 concentrations monitored using the device correlated with the therapeutic response of the patients with DED. Our enhanced SiNW biosensor device demonstrated its potential as an alternative tool for real-time diagnosis and monitoring for prognostic prediction toward point-of-care testing for DED.