Surface modification of PVDF ultrafiltration membranes using spacer arms and synthetic receptors for virus capturing and separation.

Although membrane technology has demonstrated outstanding pathogen removal capabilities, current commercial membranes are insufficient for removing small viruses at trace levels due to certain limitations. The theoretical and practical significance of developing a new form of hydrophilic, anti-fouling, and virus-specific ultra-purification membrane with high capturing and separation efficiency, stability, and throughput for water treatment is of the utmost importance. In this study, molecularly imprinted membranes (MIMs) were fabricated from polyvinylidene fluoride (PVDF) membranes utilizing novel surface hydrophilic modification techniques, followed by the immobilization of virus-specific molecularly imprinted nanoparticles (nanoMIPs) as synthetic receptors. Three distinct membrane functionalization strategies were established and optimized for the first time: membrane functionalization with (i) polyethyleneimine (PEI) and dopamine (DOP), (ii) PEI and 3-(chloropropyl)-trimethoxysilane (CTS), and (iii) chitosan (CS). Hydrophilicity was enhanced significantly as a result of these modification strategies. Additionally, the modifications enabled spacer arms between the membrane surface and the nanoMIPs to decrease steric hindrance. The surface chemistry, morphology, and membrane performance results from the characterization analysis of the MIMs demonstrated excellent hydrophilicity (e.g., the functionalized membrane presented 37.84° while the unmodified bare membrane exhibited 128.94° of water contact angle), higher permeation flux (145.96 L m-2 h-1 for the functionalized membrane), excellent uptake capacity (up to 99.99 % for PEI-DOP-MIM and CS-MIM), and recovery (more than 80 % for PEI-DOP-MIM). As proof of concept, the cutting-edge MIMs were able to eliminate the model adenoviruses up to 99.99 % from water. The findings indicate that the novel functionalized PVDF membranes hold promise for implementation in practical applications for virus capture and separation.

Computationally Designed Epitope-Mediated Imprinted Polymers versus Conventional Epitope Imprints for the Detection of Human Adenovirus in Water and Human Serum Samples.

Detection of pathogenic viruses for point-of-care applications has attracted great attention since the COVID-19 pandemic. Current virus diagnostic tools are laborious and expensive, while requiring medically trained staff. Although user-friendly and cost-effective biosensors are utilized for virus detection, many of them rely on recognition elements that suffer major drawbacks. Herein, computationally designed epitope-imprinted polymers (eIPs) are conjugated with a portable piezoelectric sensing platform to establish a sensitive and robust biosensor for the human pathogenic adenovirus (HAdV). The template epitope is selected from the knob part of the HAdV capsid, ensuring surface accessibility. Computational simulations are performed to evaluate the conformational stability of the selected epitope. Further, molecular dynamics simulations are executed to investigate the interactions between the epitope and the different functional monomers for the smart design of eIPs. The HAdV epitope is imprinted via the solid-phase synthesis method to produce eIPs using in silico-selected ingredients. The synthetic receptors show a remarkable detection sensitivity (LOD: 102 pfu mL-1) and affinity (dissociation constant (Kd): 6.48 × 10-12 M) for HAdV. Moreover, the computational eIPs lead to around twofold improved binding behavior than the eIPs synthesized with a well-established conventional recipe. The proposed computational strategy holds enormous potential for the intelligent design of ultrasensitive imprinted polymer binders.

Current trends in COVID-19 diagnosis and its new variants in physiological fluids: Surface antigens, antibodies, nucleic acids, and RNA sequencing.

Rapid, highly sensitive, and accurate virus circulation monitoring techniques are critical to limit the spread of the virus and reduce the social and economic burden. Therefore, point-of-use diagnostic devices have played a critical role in addressing the outbreak of COVID-19 (SARS-CoV-2) viruses. This review provides a comprehensive overview of the current techniques developed for the detection of SARS-CoV-2 in various body fluids (e.g., blood, urine, feces, saliva, tears, and semen) and considers the mutations (i.e., Alpha, Beta, Gamma, Delta, Omicron). We classify and comprehensively discuss the detection methods depending on the biomarker measured (i.e., surface antigen, antibody, and nucleic acid) and the measurement techniques such as lateral flow immunoassay (LFIA), enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), microarray analysis, clustered regularly interspaced short palindromic repeats (CRISPR) and biosensors. Finally, we addressed the challenges of rapidly identifying emerging variants, detecting the virus in the early stages of infection, the detection sensitivity, selectivity, and specificity, and commented on how these challenges can be overcome in the future.

Cancer biomarker detection in human serum samples using nanoparticle decorated epitope-mediated hybrid MIP.

The determination of disease-associated molecules at trace amounts is a key factor for early and efficient diagnosis from human body fluids. Herein, an ultrasensitive electrochemical sensor based on hybrid epitope imprinting and nanomaterial amplification was developed. The hybrid epitope imprinting was achieved by electropolymerization in the presence of two computationally selected and cysteine modified epitopes of neuron specific enolase (NSE), as-synthesized gold nanoparticles (AuNPs), and functional monomer. The AuNPs decorated epitope-mediated hybrid MIPs, as well as the standard hybrid MIPs, were utilized for the preparation of electrochemical sensors to demonstrate the impact of nanomaterial's modification in the polymer network for biomarker sensing. The fabrication process of both sensor types was investigated by employing cyclic voltammetry, square wave voltammetry, atomic force microscopy, and scanning electron microscopy. The biomarker assay using the standard hybrid MIPs resulted in 2.5-fold higher sensitivity compared to single epitope imprints, whereas the AuNP-hybrid MIPs enhanced the sensitivity level to a great extent and allowed the recognition of NSE in human serum in a concentration range of 25-4000 pg/mL. Comparative selectivity studies with non-imprinted polymer resulted in an imprinting factor of 4.2, confirming the high target selectivity of AuNP-MIP cavities. Cross-reaction of the sensor with four reference molecules (dopamine, bovine serum albumin, glucose and elongated peptide) was negligible. As compared to current strategies for epitope imprinting which rely on single epitopes for the formation of molecular cavities, the hybrid epitope-MIPs, particularly with the inclusion of AuNPs have provided more desirable sensing platforms with high sensitivity, affinity and specificity.

Ultrasensitive nonenzymatic electrochemical glucose sensor based on gold nanoparticles and molecularly imprinted polymers.

A non-enzymatic electrochemical glucose sensor with high sensitivity and selectivity was developed using gold nanoparticles-decorated molecularly imprinted polymers (AuNP-MIPs). The AuNP-MIPs were synthesized on a gold surface by multistep amperometry using the optimized conditions and in-house synthesized gold nanoparticles in the presence of glucose as the template. The AuNP-MIPs were investigated by employing atomic force microscopy (AFM), scanning electron microscopy (SEM) and electrochemical techniques to confirm successful fabrication of the sensor. The electrochemical measurements for glucose binding on the AuNP-MIP sensor revealed a high affinity toward glucose with a dissociation constant (Kd) of 3 × 10-8 M whereas the MIPs without AuNPs could not detect even the highest concentration of the investigation range (1.25 nM-2.56 µM). The comparative rebinding studies with AuNP-MIP and non-imprinted polymer (AuNP-NIP) exhibited an excellent selectivity toward glucose. The specificity of AuNP-MIP sensor was further investigated by studying with interfering compounds (sucrose, dopamine, starch, and bovine serum albumin), resulting in negligible cross-reactivity except for sucrose. The behavior of imprinted polymers in fluid solvents was also investigated by employing the AFM for the first time. The sensor could detect glucose in human serum with a detection limit of 1.25 nM and preserved its stability up to around 95% during a storage time of 40 days. Hence, such a sensor demonstrates a promising future for the detection of clinically relevant small molecules with its facile, cheap, and highly sensitive nature.

Significance of nanomaterials in electrochemical glucose sensors: An updated review (2016-2020).

The last decade has witnessed an immense demand for the development of new glucose biosensors. The research has mainly focused on achieving biocompatible and improved sensing capabilities as compared to the current technologies, which opens new directions toward more efficient glucose sensors. These sensing platforms have been continuously evolving with the contribution of novel materials, such as gold, platinum, metal alloys/adatom, graphene, composites and glucose-specific organic materials, owing to their electrocatalytic response to the oxidation of glucose. The chief motive of this review is to cover the recent advances on enzymatic and non-enzymatic glucose sensors evolved in the last four years. We discuss the sensor fabrication methods, the materials and nanostructures involved, the detection principles and the performance of the sensors in whole blood, saliva, urine or interstitial fluids in detail.