Synchronous Diagnosis of Respiratory Viruses Variants via Receptonics Based on Modeling Receptor-Ligand Dynamics.

The transmission and pathogenesis of highly contagious fatal respiratory viruses are increasing, and the need for an on-site diagnostic platform has arisen as an issue worldwide. Furthermore, as the spread of respiratory viruses continues, different variants have become the dominant circulating strains. To prevent virus transmission, the development of highly sensitive and accurate on-site diagnostic assays is urgently needed. Herein, a facile diagnostic device is presented for multi-detection based on the results of detailed receptor-ligand dynamics simulations for the screening of various viral strains. The novel bioreceptor-treated electronics (receptonics) device consists of a multichannel graphene transistor and cell-entry receptors conjugated to N-heterocyclic carbene (NHC). An ultrasensitive multi-detection performance is achieved without the need for sample pretreatment, which will enable rapid diagnosis and prevent the spread of pathogens. This platform can be applied for the diagnosis of variants of concern in clinical respiratory virus samples and primate models. This multi-screening platform can be used to enhance surveillance and discriminate emerging virus variants before they become a severe threat to public health.

Second Skin as Self-Protection Against γ-Hydroxybutyrate.

γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.

Discrimination of the H1N1 and H5N2 Variants of Influenza A Virus Using an Isomeric Sialic Acid-Conjugated Graphene Field-Effect Transistor.

There has been a continuous effort to fabricate a fast, sensitive, and inexpensive system for influenza virus detection to meet the demand for effective screening in point-of-care testing. Herein, we report a sialic acid (SA)-conjugated graphene field-effect transistor (SA-GFET) sensor designed using α2,3-linked sialic acid (3'-SA) and α2,6-linked sialic acid (6'-SA) for the detection and discrimination of the hemagglutinin (HA) protein of the H5N2 and H1N1 viruses. 3'-SA and 6'-SA specific for H5 and H1 influenza were used in the SA-GFET to capture the HA protein of the influenza virus. The net charge of the captured viral sample led to a change in the electrical current of the SA-GFET platform, which could be correlated to the concentration of the viral sample. This SA-GFET platform exhibited a highly sensitive response in the range of 101-106 pfu mL-1, with a limit of detection (LOD) of 101 pfu mL-1 in buffer solution and a response time of approximately 10 s. The selectivity of the SA-GFET platform for the H1N1 and H5N2 influenza viruses was verified by testing analogous respiratory viruses, i.e., influenza B and the spike protein of SARS-CoV-2 and MERS-CoV, on the SA-GFET. Overall, the results demonstrate that the developed dual-channel SA-GFET platform can potentially serve as a highly efficient and sensitive sensing platform for the rapid detection of infectious diseases.

Real-time monitoring of serotonin with highly selective aptamer-functionalized conducting polymer nanohybrids.

Adequate serotonin levels are pivotal to human well-being; thus, serotonin can be used as a biomarker because it regulates a wide range of physical and psychological functions. As an imbalance of serotonin is highly likely to initiate the pathogenesis of various disorders, monitoring serotonin levels in real time is in high demand for the early detection of disease. We fabricated a field-effect transistor (FET) biosensor based on aptamer-immobilized conducting polymer nanohybrids, which showed an instantaneous response toward serotonin in solution. The mechanism of serotonin detection was based on aptamer deformation after aptamer-ligand interaction and the consequential decrease in the charge carrier density of the FET template. Docking simulations with AutoDock/Vina and PyMOL were successfully used to investigate the binding site of serotonin in the loop structure of the aptamer. The fabricated FET template showed high sensitivity toward serotonin in the range of 10 fM to 100 nM, and the limit of detection (LOD) was exceptionally low at 10 fM. Moreover, the selectivity toward serotonin was confirmed by observing no signal after the injection of structural analogs, functional analogs and excess physiological biomolecules. The potential clinical application of this sensor was confirmed because it remained consistent when the buffer solution was exchanged for artificial serum or artificial cerebrospinal fluid (CSF). † S.G.L. and S.E.S. contributed equally to this work.

Wireless portable bioelectronic nose device for multiplex monitoring toward food freshness/spoilage.

Monitoring food freshness/spoilage is important to ensure food quality and safety. Current methods of food quality monitoring are mostly time-consuming and labor intensive processes that require massive analytical equipment. In this study, we developed a portable bioelectronic nose (BE-nose) integrated with trace amine-associated receptor (TAAR) nanodiscs (NDs), allowing food quality monitoring via the detection of food spoilage indicators, including the biogenic amines cadaverine (CV) and putrescine (PT). The olfactory receptors TAAR13c and TAAR13d, which have specific affinities for CV and PT, were produced and successfully reconstituted in ND structures. TAAR13 NDs BE-nose-based side-gated field-effect transistor (SG-FET) system was constructed by utilizing a graphene micropattern (GM) into which two types of olfactory NDs (TAAR13c ND and TAAR13d ND) were introduced, and this system showed ultrahigh sensitivity for a limit of detection (LOD) of 1 fM for CV and PT. Moreover, the binding affinities between the TAAR13 NDs and the indicators were confirmed by a tryptophan fluorescence quenching assay and biosimulations, in which the specific binding site was confirmed. Gas-phase indicators were detected by the TAAR13 NDs BE-nose platform, and the LODs for CV and PT were confirmed to be 26.48 and 7.29 ppb, respectively. In addition, TAAR13 NDs BE-nose was fabricated with commercial gas sensors as a portable platform for the measurement of NH3 and H2S, multiplexed monitoring was achieved with similar performance, and the change ratio of the indicators was observed in a real sample. The integration of commercial gas sensors on a BE-nose enhanced the accuracy and reliability for the quality monitoring of real food samples. These results indicate that the portable TAAR13 NDs BE-nose can be used to monitor CV and PT over a wide range of concentrations, therefore, the electronic nose platform can be utilized for monitoring the freshness/spoilage step in various foods.

In situ, real-time, colorimetric detection of γ-hydroxybutyric acid (GHB) using self-protection products coated with chemical receptor-embedded hydrogel.

Due to the increase in drug-facilitated sexual assault (DFSA) enabled by the illegal use of drugs, there have been constant demands for simple methods that can be used to protect oneself against crime in real life. γ-Hydroxybutyric acid (GHB), a central nervous system depressant, is one of the most dangerous drugs for use in DFSA because it is colorless and has slow physiological effects, which pose challenges for developing in situ, real-time GHB monitoring techniques. In this study, we developed a method for in situ colorimetric GHB detection using various self-protection products (SPPs) coated with 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI) as a chemical receptor embedded in hydrogels. Additionally, smartphone-based detection offers enhanced colorimetric sensitivity compared to that of the naked eye. The developed SPPs will help address drug-facilitated social problems.

Wearable Cortisol Aptasensor for Simple and Rapid Real-Time Monitoring.

The necessity of managing stress levels is becoming increasingly apparent as the world suffers from different kinds of stresses including the extent of pandemic, the corona virus disease 2019 (COVID-19). Cortisol, a clinically confirmed stress hormone related to depression and anxiety, affects individuals mentally and physically. However, current cortisol monitoring methods require expert personnel, large and complex machines, and long time for data analysis. Here, we present a flexible and wearable cortisol aptasensor for simple and rapid cortisol real-time monitoring. The sensing channel was produced by electrospinning conducting polyacrylonitrile (PAN) nanofibers (NFs) and subsequent vapor deposition of carboxylated poly(3,4-ethylenedioxythiophene) (PEDOT). The conjugation of the cortisol aptamer on the PEDOT-PAN NFs provided the critical sensing mechanism for the target molecule. The sensing test was performed with a liquid-ion gated field-effect transistor (FET) on a polyester (polyethylene terepthalate). The sensor performance showed a detection limit of 10 pM (<5 s) and high selectivity in the presence of interference materials at 100 times higher concentrations. The practical usage and real-time monitoring of the cortisol aptasensor with a liquid-ion gated FET system was demonstrated by successful transfer to the swab and the skin. In addition, the real-time monitoring of actual sweat by applying the cortisol aptasensor was also successful since the aptasensor was able to detect cortisol approximately 1 nM from actual sweat in a few minutes. This wearable biosensor platform supports the possibility of further application and on-site monitoring for changes of other numerous biomarkers.

In-situ food spoilage monitoring using a wireless chemical receptor-conjugated graphene electronic nose.

Monitoring food spoilage is one of the most effective methods for preventing food poisoning caused by biogenic amines or microbes. Therefore, various analytical techniques have been introduced to detect low concentrations of cadaverine (CV) and putrescine (PT), which are representative biogenic polyamines involved in food spoilage (5-8 ppm at the stage of initial decomposition after storage for 5 days at 5 °C and 17-186 ppm at the stage of advanced decomposition after storage for 7 days at 5 °C). Although previous methods showed selective CV and PT detection even at low concentrations, the use of these methods remains challenging in research areas that require in-situ, real-time, on-site monitoring. In this study, we demonstrated for the first time an in-situ high-performance chemical receptor-conjugated graphene electronic nose (CRGE-nose) whose limits of detection (LODs), 27.04 and 7.29 ppb, for CV and PT are up to 102 times more sensitive than those of conventional biogenic amine sensors. Specifically, the novel chemical receptors 2,7-bis(3-morpholinopropyl)benzo[lmn][3,8] phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiMor (NPM)) and 2,7-bis(2-((3-morpholinopropyl)amino)ethyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiEtAmMor (NPEAM)) were designed on the basis of density functional theory (DFT) calculations, and their interaction mechanism was characterized by a DFT 3D simulation. Interestingly, the CRGE-nose was connected on a micro sim chip substrate via wire bonding and then integrated into wireless portable devices, resulting in a cost-effective, high-performance prototype CRGE-nose device capable of on-site detection. The portable CRGE-nose can be used for in-situ monitoring of CV and PT concentration changes as low as 27.04 and 7.29 ppb in real meats such as pork, beef, lamb and chicken.