Real-time, specific, and label-free transistor-based sensing of organophosphates in liquid.

Organophosphates (OP), commonly used in agriculture and as chemical warfare agents, pose significant environmental risks, necessitating real-time, low-cost OP detection methods. In particular, liquid-phase OP sensing with minimal sample volumes is crucial. While several methods allow rapid detection of low concentrations of OP vapors, they are effective only in the short term, while vapors are still being produced. Many OP compounds are semi-volatile, leading to the contamination of water, soil, and surfaces, posing a risk of secondary, long-term exposure. Detecting this contamination requires methods that can be directly applied to droplets of the affected medium. Currently, no method provides the desired combination of ultra-sensitivity, quantitative detection, rapid response, and low-cost for detecting OPs in liquid samples. This study aims to demonstrate quantitative, low-cost, real-time, specific, and label-free OP sensing in ultra-small samples using a transistor-based approach. The current work employs the 2-(4-Aminophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (aminophenyl-HFIP) functionalized meta-nano-channel field-effect chemical sensor (MNChem sensor) to monitor the organophosphate, diethyl cyanophosphonate (DCNP), in liquid samples. The silicon component of the MNChem is fabricated using a complementary metal-oxide semiconductor (CMOS) process, and the amine-based chemical functionalization of the sensing area is performed post-fabrication. The MNChem sensor provides electrostatic control over the source-drain current (IDS), allowing an optimized channel configuration that efficiently transduces localized OP recognition events into significant IDS variations. Sensing is performed using 0.5 µL buffer solution to simulate a miniature field-deployable sensor for on-site liquid analysis. We report the sensing of DCNP with a limit-of-detection of 100 fg/mL, a dynamic range of 9 orders of magnitude, and excellent linearity (≥0.97) and sensitivity. Control measurements confirm the specificity and reliability of the sensor's response, validating its applicability. This study introduces a novel method for OP detection in contaminated droplets using a low-cost disposable transistor technology.

Addressing the challenge of solution gating in biosensors based on field-effect transistors.

Transistor-based biosensing (BioFET) is a long-enduring vision for next generation medical diagnostics. The study addresses a challenge associated with the BioFET solution gating. The standard BioFET sensing measurement involves sweeping of the solution gate (Vsol) with a concurrent measurement of the source-drain current (IDS). This IDS-Vsol sweep poses a great challenge, as Vsol does not only determine IDS, but also determines the pH levels, ion concentrations, and electric fields at the sensing area double layer accommodating the biomolecules. Therefore, inevitably, an IDS-Vsol sweep implies that the sensing area double layer is not in an electrochemical equilibrium, but rather in a continuous transient state as electrochemical potential gradients induce transient ion currents continuously affecting double layer hosting the biomolecules and the biological interactions. This challenge calls for a BioFET design which permits IDS sweeping from an off-state to an on-state while keeping Vsol constant and the double layer sensing area in electrochemical equilibrium. The study explores a BioFET design addressing this challenge by decoupling the solution potential from IDS gating. Specific and label-free sensing of ferritin in 0.5 µL drops of 1:100 diluted plasma is pursued. We show an excellent sensing performance once the solution potential and IDS gating are decoupled, with a limit-of-detection of 10 fg/ml, a dynamic range of 10 orders of magnitude in ferritin concentration and excellent linearity and sensitivity. In contrast, a poor sensing performance is recorded for the conventional Vsol sweep performed in parallel to the above. Extensive control measurements quantifying the non-specific signals are reported.

NAGase sensing in 3% milk: FET-based specific and label-free sensing in ultra-small samples of high ionic strength and high concentration of non-specific proteins.

Biosensing with biological field-effect transistors (bioFETs) is a promising technology toward specific, label-free, and multiplexed sensing in ultra-small samples. The current study employs the field-effect meta-nano-channel biosensor (MNC biosensor) for the detection of the enzyme N-acetyl-beta-D-glucosaminidase (NAGase), a biomarker for milk cow infections. The measurements are performed in a 0.5 µL drops of 3% commercial milk spiked with NAGase concentrations in the range of 30.3 aM-3.03 µM (Note that there is no background NAGase concentration in commercial milk). Specific and label-free sensing of NAGase is demonstrated with a limit-of-detection of 30.3 aM, a dynamic range of 11 orders of magnitude and with excellent linearity and sensitivity. Additional two important research outcomes are reported. First, the ionic strength of the examined milk is ∼120 mM which implies a bulk Debye screening length <1 nm. Conventionally, a 1 nm Debye length excludes the possibility of sensing with a recognition layer composed of surface bound anti-NAGase antibodies with a size of ∼10 nm. This apparent contradiction is removed considering the ample literature reporting antibody adsorption in a predominantly surface tilted configuration (side-on, flat-on, etc.). Secondly, milk contains a non-specific background protein concentration of 33 mg/ml, in addition to considerable amounts of micron-size heterogeneous fat structures. The reported sensing was performed without the customarily exercised surface blocking and without washing of the non-specific signal. This suggests that the role of non-specific adsorption to the BioFET sensing signal needs to be further evaluated. Control measurements are reported.

From sensing interactions to controlling the interactions: a novel approach to obtain biological transistors for specific and label-free immunosensing.

Antibody-antigen interactions are shaped by the solution pH level, ionic strength, and electric fields, if present. In biological field-effect transistors (BioFETs), the interactions take place at the sensing area in which the pH level, ionic strength and electric fields are determined by the Poisson-Boltzmann equation and the boundary conditions at the solid-solution interface and the potential applied at the solution electrode. The present study demonstrates how a BioFET solution electrode potential affects the sensing area double layer pH level, ionic strength, and electric fields and in this way shapes the biological interactions at the sensing area. We refer to this as 'active sensing'. To this end, we employed the meta-nano-channel (MNC) BioFET and demonstrate how the solution electrode can determine the antibody-antigen equilibrium constant and allows the control and tuning of the sensing performance in terms of the dynamic range and limit-of-detection. In the current work, we employed this method to demonstrate the specific and label-free sensing of Alpha-Fetoprotein (AFP) molecules from 0.5 µL drops of 1 : 100 diluted serum. AFP was measured during pregnancy as part of the prenatal screening program for fetal anomalies, chromosomal abnormalities, and abnormal placentation. We demonstrate AFP sensing with a limit-of-detection of 10.5 aM and a dynamic range of 6 orders of magnitude in concentration. Extensive control measurements are reported.

Geo-environmental factors and the effectiveness of mulberry leaf extract in managing malaria.

Malaria prevalence has become medically important and a socioeconomic impediment for the endemic regions, including Purulia, West Bengal. Geo-environmental variables, humidity, altitude, and land use patterns are responsible for malaria. For surveillance of the endemic nature of Purulia's blocks, statistical and spatiotemporal factors analysis have been done here. Also, a novel approach for the Pf malaria treatment using methanolic leaf extract of Morus alba S1 has significantly reduced the parasite load. The EC50 value (1.852) of the methanolic extract of M. alba S1 with P. falciparum 3D7 strain is close to the EC50 value (0.998) of the standard drug chloroquine with the same chloroquine-sensitive strain. Further studies with an in-silico model have shown successful interaction between DHFR and the phytochemicals. Both 1-octadecyne and oxirane interacted favourably, which was depicted through GC-MS analysis. The predicted binary logistic regression model will help the policy makers for epidemiological surveillance in malaria-prone areas worldwide when substantial climate variables create a circumstance favourable for malaria. From the in vitro and in silico studies, it can be concluded that the methanolic extract of M. alba S1 leaves were proven to have promising antiplasmodial activity. Thus, there is a scope for policy-driven approach for discovering and developing these lead compounds and undermining the rising resistance to the frontline anti-malarial drugs in the world.

Understanding the role of soft linkers in designing hepatzine-based polymeric frameworks as heterogeneous (photo)catalyst.

The emerging class of heptazine-based polymeric materials has shown potential candidature as photocatalyst materials for hydrogen evolution. At the same time, they have shown promising application as solid base materials to catalyse various organic transformations. Thus, the material design rationale needs to be developed around the heptazine-based polymeric frameworks in order to specifically design task specific materials. Herein, we utilised controlled reaction conditions to synthesize the desired polymeric networks with trichloroheptazine as precursor. Material design strategy employed nitrogen rich [tris(2-aminoethylamine) and hydrazine] as soft linkers to understand the effect on band structure of developed heptazine-based polymeric networks. The developed polymeric networks were explored as platform to study systematically the effect on their respective photophysical properties and understand their surface basicity. The framework having aminoalkyl linker showed superior activity in photocatalysis as well as heterogeneous base catalysis. Further, model catalysts revealed the importance of N-atoms as active basic sites in these systems.

Quantum dot-sensitized O-linked heptazine polymer photocatalyst for the metal-free visible light hydrogen generation.

Metal-free organic polymer photocatalysts have attracted dramatic attention in the field of visible light-induced hydrogen evolution reaction (HER). Herein, we showed a polymeric O-linked heptazine polymer (OLHP) decorated with S, N co-doped graphene quantum dots (S,N-GQDs) as a photosensitizer to generate hydrogen upon quantum dot sensitization. Both of these heptazine-based systems show effective photosensitization with strong π-π interactions and enhanced photocatalytic H2 generation (24 times) as metal-free systems. Electrochemical impedance and optical measurements show effective charge transfer kinetics with decreased charge recombination, which is responsible for the enhanced photocatalytic activity. As a result, a significant high apparent quantum yield (AQY) with highest value of 10.2% was obtained for our photocatalyst OLHP/S,N-GQD10.