DNA Aptamer Integrated Hydrogel Nanocomposites on Screen Printed Gold Electrodes for Point-of-Care Detection of Testosterone in Human Serum.

This work describes the development and evaluation of a novel electrochemical aptasensor for testosterone detection. The sensor utilizes a specifically designed DNA immobilized on a screen-printed gold electrode (SPGE) modified with a conductive hydrogel and gold nanoparticles (HG/NP) composite. The aptasensor exhibited a dose-dependent response to testosterone (0.05 to 50 ng/mL) with a detection limit of 0.14 ng/mL and a good sensitivity of 0.23 µA ng-1 mL cm-2. The sensor displayed excellent selectivity towards testosterone compared to structurally similar steroid hormones. Importantly, the incorporation of HG/NP not only improved the sensor's conductivity but also acted as an antifouling layer, minimizing signal interference from non-specific biomolecule interactions in complex biological samples like human serum. The results obtained from the aptasensor showed good correlation with a standard ELISA method, demonstrating its effectiveness in real-world scenarios.

Fabrication of an all-in-one self-enhanced solid-state electrochemiluminescence sensing platform for the selective detection of spermine.

The fabrication of an all-in-one solid-state ECL sensing platform is beneficial not only for expediting the miniaturization of sensing devices, but also, more importantly, for enabling point-of-care applications. In the present work, a self-enhanced solid-state ECL sensing platform is fabricated using newly synthesised silica polyethylene nanoparticles (SiO2-PEI NPs) which generate a co-reactant in situ and easily self-assemble with Ru(bpy)32+ and shows selective and sensitive detection of spermine at physiological pH (7.4). Spermine induces the maximum ECL emission intensity compared to other biogenic amines due to the presence of two secondary amines. A possible ECL reaction mechanism has been proposed based on CV and ECL experiments, DFT calculations, and in situ ECL spectrum analysis. The developed solid-state sensor showed a linear increase in ECL intensity with increasing spermine concentration in the range of 10 nM to 100 nM with an LOD of 12.2 nM. Compared to other biogenic amines in previous works, chemically synthesised SiO2-PEI NPs used in the present study act as an effective label- and enzyme-free sensor, and the new method is observed to be simple and cost-effective, to overcome various limitations of solution-phase ECL and to avoid the usage of any noble metals.

Quantum chemical investigation of meta-xylylene based one-dimensional polymer chain.

We have investigated unsubstituted and methyl substituted polyradical chains of meta-xylylene by using density functional theory-broken symmetry methodology (DFT-BS). Optimization of geometry in the high-spin and low-spin states have been done at B3LYP/6-31G(d,p) and M06-2X/6-31G(d,p) levels in unrestricted methodology. Single-point calculations on the high-spin optimized geometries have been done by using the 6-311G(d,p) basis set. Each polyradical has been found to be nonplanar with a high-spin ground state. Each has a coupling constant larger than thermal energy. For each group of polyradicals, the coupling constant has been found to exponentially decrease with increase in the number of phenylene groups. The B3LYP infinite chain limit has been estimated for both the unsubstituted and substituted polyradicals. The individual inter-radical-site coupling constants have been estimated for the triradicals and tetraradicals using HDVV Hamiltonian in ORCA 3.0.1 code. These are also generally large and positive, revealing a strong intersite ferromagnetic interaction. The intersite coupling constant too decreases with increasing distance between the radical centers. Finally, we have used CRYSTAL09 package for calculations on the infinitely long one-dimensional and periodic polyradical chains. The coupling constants estimated from the periodic calculations are quite large at about 500 cm(-1) and somewhat greater than the limiting values calculated for the polyradicals with an increasing number of phenylene groups. This happens as the individual polyradicals of increasing size progressively deviate from periodicity, and thereby lessens the strength of through-bond spin-spin coupling. The calculated band gap of ∼4.5 eV indicates that the infinitely long one-dimensional chains must be ferromagnetic and electron insulators.

Metaphenylene-based nitroxide diradicals: a protocol to calculate intermolecular coupling constant in a one-dimensional chain.

Intramolecular magnetic exchange coupling constants are determined for seven isolated metaphenylene-based dinitroxide diradicals by unrestricted density functional methodology (UDFT) using a number of hybrid functionals such as B3LYP, B3LYP-D3, M06-2X, HSE, and LC-ωPBE. Geometry optimizations for both triplet and broken symmetry solutions are performed with the 6-311G(d,p) basis set for all the molecules. In all cases, B3LYP somewhat overestimates the coupling constant, and M06-2X produces a more realistic value. The range-separated HSE and LC-ωPBE functional yield large deviations from experiment. The nature of spin coupling agrees with the spin alternation rule and the calculated spin densities, in conjunction with the McConnell rule. It can also be explained in terms of the nondisjoint Single Occupied Molecular Orbital effect. Furthermore, it correlates with the calculated NICS(1) isotropic and zz and hyperfine coupling constants. We also put forward a method for the determination of the intramolecular (J) and intermolecular (J') coupling constants from quantum chemical calculations on a one-dimensional chain of weakly bound diradicals. Two expressions are derived for the energies of different spin states in terms of J and J'. Exemplary UDFT computations are done on the N-mers (N = 2-6) of two diradicals for which the crystal coordinates are available. The intramolecular and intermolecular coupling constants are determined from the calculated UDFT energies. These are indeed in general agreement with the measured coupling constants.

Theoretical investigation of stilbene as photochromic spin coupler.

Density functional theory (DFT) based calculations are used here to investigate the magnetic behavior, spectroscopic transitions, and possible photomagnetic properties of stilbene derivatives using photochromicity of cis- and trans-forms of the parent molecule. Nitronyl nitroxide (NN), iminonitroxide (IN), tetrathiafulvalene cation (TTF), and verdazyl (VER) are used as monoradical centers at the p, p' positions. The B3LYP functional with the usual broken symmetry approach and a sufficiently large basis set is chosen to obtain reliable estimates of the intramolecular exchange coupling constants (J). It is found that, with stilbene as a spacer, the coupling of TTF with NN, IN, and VER is always antiferromagnetic with J being generally large and negative. Although J values obtained for cis- and trans-forms are both negative, the difference in J values is quite large. Spectroscopic transition energies and corresponding oscillator strengths of cis- and trans-stilbene diradicals are estimated by time-dependent (TD)-DFT calculations using the same functional. Interestingly, the spectral features of the diradicals are similar to those of cis- and trans-stilbene, which suggests that stilbene diradicals would have good photoswitching properties. Finally, we show that, when these diradicals are placed in a matrix, photochromicity would be accompanied by a significant change in paramagnetic susceptibility.

Theoretical investigation of photomagnetic properties of oxoverdazyl-substituted pyrenes.

We have investigated the ground state spin of 10 pairs of possible photochromic diradical isomers by quantum chemical methods. Dihydrogen pyrenes and dinitrile pyrenes have been chosen as spacers with radical centers attached at (1,7) and (1,8) locations. Oxoverdazyl has served as a radical center, and both C and N linkages have been investigated. Triplet molecular geometries have been optimized at the UB3LYP/6-311G(d,p) level. Single-point calculations on triplet and broken symmetry states have been performed using the 6-311++G(d,p) basis set. Careful designs have led to the prediction of strongly coupled dihydropyrene (DHP) isomers, and the cyclophenadiene (CPD) isomers have always been found as weakly coupled. The effect of the functional M06-2X has been investigated. Calculated TDDFT spectra have been sufficient to guarantee photochromism of the designed diradicals. It has been estimated that compounds of diradicals with large coupling constants in the DHP form would show a pronounced change in molar susceptibility on photoconversion. This has led us to identify two molecules that can serve as a photomagnetic switch at room temperature.

High magnetic exchange coupling constants: a density functional theory based study of substituted Schlenk diradicals.

The Schlenk diradical has been known since 1915. After a detailed experimental work by Rajca, its magnetic nature has remained more or less unexplored. We have investigated by quantum chemical calculations the nature of magnetic coupling in 11 substituted Schlenk diradicals. Substitution has been considered at the fifth carbon atom of the meta-phenylene moiety. The UB3LYP method has been used to study 12 diradicals including the original one. The 6-311G(d,p) basis set has been employed for optimization of molecular geometry in both singlet and triplet states for each species. The singlet optimization has led to the optimization of the broken-symmetry structure for 10 species including the unsubstituted one. This development makes it possible to carry out further broken symmetry calculations in two ways. The triplet calculation has been done using 6-311++G(d,p) basis set and the optimized triplet geometry in both procedures. The broken symmetry calculations have used the optimized geometries of either the triplet states or the broken symmetry solutions. The first method leads to the prediction of electron paramagnetic resonance (EPR) compatible magnetic exchange coupling constant (J) in the range 517-617 cm(-1). A direct optimization of the broken symmetry geometry gives rise to a lower estimate of J, in the range of 411-525 cm(-1) and compatible with macroscopic Curie studies. The calculated J for the unsubstituted Schlenk diradical is 512 cm(-1) that can be compared with 455 cm(-1) estimated by Rajca. In both cases, introduction of groups with +M and +I effects (Ingold's notation) decreases the J value from that for the unsubstituted Schlenk diradical while -I and -M groups at the same position increases J. These trends have been explained in terms of Hammett constants, atomic spin densities, and dihedral angles.

On the photomagnetism of nitronyl nitroxide, imino nitroxide, and verdazyl-substituted azobenzene.

The cis- and trans-azobenzenes are known as photochromic isomers with the trans- converting into the cis-form and vice versa upon irradiation with specific wavelengths. We have quantum chemically investigated the cis- and trans-forms of substituted azobenzene diradicals, with two nitronyl nitroxides, imino nitoxides, or verdazyls at para positions and serving as monoradical centers, to determine whether they can exhibit a photoassisted magnetic crossover. Geometries of both substituted and unsubstituted molecules have been optimized by density functional (DF) method UB3LYP using the 6-311G(d,p) basis set. Optimization of the geometry of the cis isomers has required special care. Single point singlet, triplet, and broken symmetry calculations have been done using 6-311++G(3df, 3pd) basis set. The magnetic exchange coupling constants have been estimated from the broken symmetry calculations. Absorption wavelengths have been estimated for both substituted and unsubstituted species from time-dependent DF treatment using restricted spin-polarized methodology RB3LYP and 6-311++G(3df, 3pd) basis set. From the similarity in the calculated absorption wavelengths for the unsubstituted and substituted azobenzenes, and the increased oscillator strengths (f) for the substituted species, we predict that the diradical isomers would be strongly photochromic. From our triplet state and broken symmetry calculations, we predict that both the cis- and the trans-diradicals are antiferromagnetically coupled. This prediction is consistent with the spin alternation rule, and the possibility of a magnetic crossover is nonexistent for these species.

Towards the development of reagent-free and reusable electrochemical aptamer-based cortisol sensor.

Continuous monitoring of stress through detecting specific biochemical markers such as cortisol plays a crucial role in the early detection of various diseases. Electrochemical aptamer sensor involving binding induced conformational change allows the continuous measurement of biomarkers. A reagent-less aptamer-based biosensing platform that allows a continuous and real-time cortisol measurement is developed in this context. The aptamer is conjugated with methylene blue, which acts as a redox reporter to probe the cortisol binding quantitatively on the sensor surface. The cortisol specific aptamers were chemically modified with amine and thiol functional groups to facilitate redox reporter conjugation and attachment of aptamer to a gold electrode, respectively. The sensor achieves a clinically meaningful cortisol concentration ranging from 0.05 ng/mL to 100 ng/mL and provides good selectivity when challenged with structurally similar targets. The reagent-less measurement capability was also demonstrated using an undiluted human serum. The newly developed cortisol sensor can enable the systemic cortisol measurement for providing insights into cortisol related clinical conditions and medical treatments.

Artificial Intelligence (AI) and Internet of Medical Things (IoMT) Assisted Biomedical Systems for Intelligent Healthcare.

Artificial intelligence (AI) is a modern approach based on computer science that develops programs and algorithms to make devices intelligent and efficient for performing tasks that usually require skilled human intelligence. AI involves various subsets, including machine learning (ML), deep learning (DL), conventional neural networks, fuzzy logic, and speech recognition, with unique capabilities and functionalities that can improve the performances of modern medical sciences. Such intelligent systems simplify human intervention in clinical diagnosis, medical imaging, and decision-making ability. In the same era, the Internet of Medical Things (IoMT) emerges as a next-generation bio-analytical tool that combines network-linked biomedical devices with a software application for advancing human health. In this review, we discuss the importance of AI in improving the capabilities of IoMT and point-of-care (POC) devices used in advanced healthcare sectors such as cardiac measurement, cancer diagnosis, and diabetes management. The role of AI in supporting advanced robotic surgeries developed for advanced biomedical applications is also discussed in this article. The position and importance of AI in improving the functionality, detection accuracy, decision-making ability of IoMT devices, and evaluation of associated risks assessment is discussed carefully and critically in this review. This review also encompasses the technological and engineering challenges and prospects for AI-based cloud-integrated personalized IoMT devices for designing efficient POC biomedical systems suitable for next-generation intelligent healthcare.