From the 1918 influenza pandemic (H1N1) until the recent 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, no efficient diagnostic tools have been developed for sensitive identification of viral pathogens. Rigorous, early, and accurate detection of viral pathogens is not only linked to preventing transmission but also to timely treatment and monitoring of drug resistance. Reverse transcription-polymerase chain reaction (RT-PCR), the gold standard method for microbiology and virology testing, suffers from both false-negative and false-positive results arising from the detection limit, contamination of samples/templates, exponential DNA amplification, and variation of viral ribonucleic acid sequences within a single individual during the course of the infection. Rapid, sensitive, and label-free detection of SARS-CoV-2 can provide a first line of defense against the current pandemic. A promising technique is non-linear coherent anti-Stokes Raman scattering (CARS) microscopy, which has the ability to capture rich spatiotemporal structural and functional information at a high acquisition speed in a label-free manner from a biological system. Raman scattering is a process in which the distinctive spectral signatures associated with light-sample interaction provide information on the chemical composition of the sample. In this prospective, we briefly discuss the development and future prospects of CARS for real-time multiplexed label-free detection of SARS-CoV-2 pathogens.

Synthetic cationic polymer-mediated synthesis of silver nanoparticles and selective antimicrobial activity of the same were demonstrated. Polyethyleneimine (PEI)-coated silver nanoparticles showed antimicrobial activity against Acinetobacter baumannii as a function of the polymeric molecular weight (MW) of PEI. Silver nanoparticles were coated with PEI of three different MWs: Ag-NP-1 with PEI exhibiting a MW of 750,000, Ag-NP-2 with PEI exhibiting a MW of 1300, and Ag-NP-3 with PEI exhibiting a MW of 60,000. These nanoparticles showed a particle size distribution of 4–20 nm. The nanoparticles exhibited potent antimicrobial activity against A. baumannii, with the minimum inhibitory concentration of Ag-NP-1, Ag-NP-2, and Ag-NP-3 on the order of 5, 10, and 5 μg/mL, respectively, and minimum bactericidal concentration of Ag-NP-1, Ag-NP-2, and Ag-NP-3 on the order of 10, 20, and 10 μg/mL, respectively. Fluorescence imaging of Ag-NPs revealed selective transfusion of Ag-NPs across the cell membrane as a function of the polymeric MW; differential interaction of the cytoplasmic proteins during antimicrobial activity was observed.

In this paper, the Lewis base character of 3-aminopropyltrimethoxysilane (3-APTMS), an imine derivative of siloxane, and an indole monomer were shown to enable the reduction of gold cations in acetone. The Lewis acid–base adduct of indole monomers and gold formed a polyindole–gold nanoparticle sol. Similarly, the Lewis acid–base adduct of 3-APTMS and gold enabled the formation of gold nanoparticles in the presence of acetone. The polyindole–gold nanoparticle sol and siloxane–gold nanoparticles underwent self-assembly into a polymeric nanofluid that was suitable for casting membranes. The use of these membranes as a potentiometric ion sensor for both cations and anions was considered; a common nonspecific ion exchange molecule, sodium tetraphenylborate, and the polymeric nanofluid were used to prepare an anion sensor and a cation sensor.

Antimicrobial surface coatings function as a contact biocide and are extensively used to prevent the growth and transmission of pathogens on environmental surfaces. Currently, scientists and researchers are intensively working to develop antimicrobial, antiviral coating solutions that would efficiently impede/stop the contagion of COVID-19 via surface contamination. Herein we present a flavonoid-based antimicrobial surface coating fabricated by laser processing that has the potential to eradicate COVID-19 contact transmission. Quercetin-containing coatings showed better resistance to microbial colonization than antibiotic–containing ones.

Effective and pH-sensitive electrochemical monitoring of L-tryptophan using noble metal nanocatalysts was evaluated in this study. This work examined the electrocatalytic influence of nanoparticles on the oxidation of amino acids with the variation of pH in working media. Bimetallic nanohybrids of palladium, silver, and gold (e.g., Pd/Ag and Pd/Au nanoparticles) were processed using organofunctionalized alkoxysilanes (3-aminopropyltrimethoxysilane (3-APTMS) and 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane (EETMOS)) via a sequential reduction pathway. Transmission electron microscopy (TEM) demonstrated the role of the alkoxysilanes in determining the size of the nanoparticles and the distribution of metals in the core-shell configuration. The cluster-like morphology of PdNPs was remodeled to form bimetallic nanomaterials (Pd-AuNPs and Pd-AgNPs) with a core-shell structure. Enhancement in the electrooxidation behavior was shown to depend on the nanomaterial and the pH of the medium. The Pd-AgNPs modified electrode exhibited high sensitivity and selectivity, with characteristic amplification in cathodic peak current at lower oxidation potentials (0.659 V, 0.782 V, and 0.890 V at pH values 4, 7, and 9, respectively) due to its greater stability. Differential pulse voltammetric (DPV) scans were recorded over a wide range of concentrations from 0.1 μM to 1000μM; the Pd-AgNPs modified electrode showed the lowest limit of detection of 0.1μM at pH 4, 0.5 μM at pH 7, and 0.5 μM at pH 9.

In this study, lithographic ceramic manufacturing was used to create solid chips out of hydroxyapatite, tricalcium phosphate, zirconia, alumina, and SiAlON ceramic. X-ray powder diffraction of each material confirmed that the chips were crystalline, with little amorphous character that could result from remaining polymeric binder, and were composed entirely out of the ceramic feedstock. Surface morphologies and roughnesses were characterized using atomic force microscopy. Human bone marrow stem cells cultured with osteogenic supplements on each material type expressed alkaline phosphatase levels, an early marker of osteogenic differentiation, on par with cells cultured on a glass control. However, cells cultured on the tricalcium phosphate-containing material expressed lower levels of ALP suggesting that osteoinduction was impaired on this material. Further analyses should be conducted with these materials to identify underlying issues of the combination of material and analysis method.

Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.

The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.

Gelatin-based hydrogels derived from hydrolysis of collagen have been extensively used in pharmaceutical and medical applications because of their biocompatibility and biodegradability. For example, gelatin-based hydrogels are finding use in drug delivery and tissue engineering because they are able to promote cell adhesion and proliferation. In addition, these hydrogels can be used as wound dressings due to their attractive fluid absorbance properties. Manufacturing technologies such as ultraviolet stereolithography and two-photon polymerization can be used to prepare structures containing photosensitive gelatin-based hydrogels. This review describes the preparation of gelatin-based hydrogels and use of these materials for biomedical applications.

Due to the recent outbreak of the Zika virus (ZIKV) in several regions, rapid, and accurate methods to diagnose Zika infection are in demand, particularly in regions that are on the frontline of a ZIKV outbreak. In this paper, three diagnostic methods for ZIKV are considered. Viral isolation is the gold standard for detection; this approach can involve incubation of cell cultures. Serological identification is based on the interactions between viral antigens and immunoglobulin G or immunoglobulin M antibodies; cross-reactivity with other types of flaviviruses can cause reduced specificity with this approach. Molecular confirmation, such as reverse transcription polymerase chain reaction (RT–PCR), involves reverse transcription of RNA and amplification of DNA. Quantitative analysis based on real-time RT–PCR can be undertaken by comparing fluorescence measurements against previously developed standards. A recently developed programmable paper-based detection approach can provide low-cost and rapid analysis. These viral identification and viral genetic analysis approaches play crucial roles in understanding the transmission of ZIKV.

Over the past twenty years, the use of rapid prototyping techniques for processing of medical devices has seen rapid growth. A number of rapid prototyping techniques currently exist for producing a broad range of medical devices using metals, ceramics, polymers, and composite materials. One promising rapid prototyping technology for creating medical devices with small scale features is two photon polymerization; this scalable photopolymerization technique enables processing of photosensitive materials such as organically-modified ceramic materials. In this study, two photon polymerization was used to produce microneedles that mimic the anatomy of the mosquito fascicle. The labrum of the mosquito was replicated in the mosquito-like microneedle. On the other hand, the maxillae of the mosquito were not replicated in the mosquito-like microneedle; the absence of these features was attributed to inadequate mechanical support of the maxillae. This study suggests that two photon polymerization and other rapid prototyping technologies may be used to produce biomimetic drug delivery devices that imitate the intricate structures found in nature.

Nanoporous electrodes, such as those made from carbon or gold, can capture and release ionic analytes at concentrations near 1 mole per liter of pore volume through capacitive charging or electrochemically reversible adsorption. In vitro studies suggest that this phenomenon can be the basis for a noninvasive, precise, and programmable drug delivery method. It would eliminate the need for bulk fluid delivery to target tissue and require only a thin electrical connection, minimizing pain and tissue disruption. We have designed effective gold electrode assemblies and observed the depletion and release phenomena using electrochemical methods and charged dyes.

Ga-doped Mg0.15Zn0.85O thin films have been grown on fused silica substrates at 350°C with four different gallium concentration values using pulsed laser deposition. X-ray diffraction results indicate that these films were textured with c-plane parallel to the substrate surface. The bandgap of the films were determined based on the absorption measurements. The bandgaps of the Ga-doped thin films shifted to higher energy with respect to that of the unalloyed Mg0.15Zn0.85O thin film due to the band filling effect of electron distribution in the conduction band. Resistivity of the films was measured with four-point probe at temperatures from 295 K to 15 K. The activation energy of the gallium dopants was extracted by fitting the temperature dependent curve of resistivity.

In this study, self-organized growth of gold nanoparticles dispersed in amorphous alumina matrices was investigated. Au/Al2O3 multilayered structures were grown on silicon (001) substrates using pulsed laser deposition. Vertical ordering of particles was examined with cross-sectional transmission electron microscopy and image Fourier transformation. Self-organization of gold nanoparticles along the vertical direction was observed in the samples grown at room temperature and 320 °C. This process occurred through two-different growth modes, known as top-on-top growth and top-on-middle growth. The driving force for the vertical ordering was attributed to long-range elastic interactions among nanoparticles during the film deposition process.

Mg0.15Zn0.85O thin films were grown on fused silica substrates at different substrate temperatures using pulsed laser deposition. X-ray diffraction and transmission electron microscopy were used to investigate the structure of the films. High resolution transmission electron microscopy showed that the film contained small grains with low angle boundaries. The optical properties of the films were investigated using absorption spectra. The bandgap energy values of the films was determined by fitting the absorption data.

We have demonstrated microscale patterning of biotin and streptaividin proteins using an athermal rapid prototyping process based on piezoelectric inkjet technology. A MEMS-based piezoelectric actuator was used to dispense picoliter quantities of fluid through micron-sized nozzles. Atomic force microscopy and Fourier infrared spectroscopy studies were performed on CAD/CAM deposited proteins that were prepared using several firing voltages. Our results indicate that piezoelectric inkjet deposition is a powerful non-contact, non-destructive process for developing high-throughput biological microarrays for use in biosensing, cell culturing, and tissue engineering.

Synthetic adhesives have largely displaced natural adhesives in the automotive, aerospace, biomedical, electronic, and marine equipment industries over the past century. We have demonstrated the thin film deposition of biological adhesives using piezoelectric inkjet technology. A MEMS based piezoelectric actuator was controlled to jet uniform fluid flow of the adhesive solution through the ink jet nozzles. Microscopic deposition of adhesives enables improved bonding for a range of advanced electronic and biomedical applications. By printing such small and spatially aligned drops, bond lines between materials are reduced, ultimately resulting in increased bond strength and structural integrity. Piezoelectric ink jet deposition of biological adhesives may greatly improve wound repair in next generation eye repair, fracture fixation, organ fixation, and wound closure.

Conventional plasma-sprayed hydroxyapatite coatings suffer from many difficulties that have limited their use in orthopaedic implants, including uneven resorption rates, poor fracture toughness, and poor adhesion to medical alloys. The placement of a diamondlike carbon buffer layer may overcome these obstacles by providing unique chemical inertness, hardness, and cell-interaction properties at the implant–tissue interface. Nanocrystalline hydroxyapatite and amorphous diamondlike carbon films were prepared by room-temperature pulsed-laser deposition of hydroxyapatite and graphite targets, respectively. Scanning electron microscopy, transmission electron microscopy, x-ray diffraction, and microscratch adhesion testing were used to determine surface morphology, interfacial structure, and adhesion of the bilayer coatings. Nanocrystalline hydroxyapatite/diamondlike carbon coatings have several potential orthopaedic applications, including use in hip prostheses.

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.