Pre-enrichment-free detection of hepatocellular carcinoma-specific ctDNA via PDMS and MEMS-based microfluidic sensor.

The growing interest in microfluidic biosensors has led to improvements in the analytical performance of various sensing mechanisms. Although various sensors can be integrated with microfluidics, electrochemical ones have been most commonly employed due to their ease of miniaturization, integration ability, and low cost, making them an established point-of-care diagnostic method. This concept can be easily adapted to the detection of biomarkers specific to certain cancer types. Pathological profiling of hepatocellular carcinoma (HCC) is heterogeneous and rather complex, and biopsy samples contain limited information regarding the tumor and do not reflect its heterogeneity. Circulating tumor DNAs (ctDNAs), which can contain information regarding cancer characteristics, have been studied tremendously since liquid biopsy emerged as a new diagnostic method. Recent improvements in the accuracy and sensitivity of ctDNA determination also paved the way for genotyping of somatic genomic alterations. In this study, three-electrode (Au-Pt-Ag) glass chips were fabricated and combined with polydimethylsiloxane (PDMS) microchannels to establish an electrochemical microfluidic sensor for detecting c.747G > T hotspot mutations in the TP53 gene of ctDNAs from HCC. The preparation and analysis times of the constructed sensor were as short as 2 h in total, and a relatively high flow rate of 30 µl/min was used during immobilization and hybridization steps. To the best of our knowledge, this is the first time a PDMS-based microfluidic electrochemical sensor has been developed to target HCC ctDNAs. The system exhibited a limit of detection (LOD) of 24.1 fM within the tested range of 2-200 fM. The sensor demonstrated high specificity in tests conducted with fully noncomplementary and one-base mismatched target sequences. The developed platform is promising for detecting HCC-specific ctDNA at very low concentrations without requiring pre-enrichment steps.

Green and Facile Synthesis of Pullulan-Stabilized Silver and Gold Nanoparticles for the Inhibition of Quorum Sensing.

Pullulan (Pull) decorated with monodisperse Ag and Au nanoparticles (NPs) was synthesized by a simple and green method. Samples were characterized by FTIR, UV-vis, NMR, XRD, TGA, SEM, XPS, DLS, and TEM. SEM images showed highly oriented microforms reported for the first time for Pull, because of the supramolecular self-assembling behavior of Pull chains. Antimicrobial and quorum sensing (QS) inhibition activities were tested against six pathogen bacteria and reporter and biomonitor strain. Pull decorated with NPs, in particular, Ag-modified ones, outperformed pristine Pull. The cell proliferation was tested with an MTT assay. NPs-decorated Pull was studied for the first time as an inhibitory agent against bacterial signal molecules and found to be a good candidate. The promising performance of AgNPs@Pull compared to the commercial antibiotic gentamicin showed that it has great potential as a therapeutic approach to overcome the bacterial resistance that has developed against conventional antibiotics.

Microwave-Assisted Synthesis of Stretchable and Transparent Poly(Ethyleneglycol-Sebacate) Elastomers with Autonomous Self-Healing and Capacitive Properties.

Introducing functional synthetic biomaterials to the literature became quite essential in biomedical technologies. For the growth of novel biomedical engineering approaches, progressive functional properties as well as the robustness of the manufacturing processes are essential. By using acid-induced epoxide ring-opening polymerizations through catalysts, a wide variety of biodegradable and functionalized biomaterials can be synthesized. Sebacic acid (SA) and poly(ethylene glycol) diglycidyl ether (PEGDGE) are amongst the FDA-approved biocompatible materials. In this study, we focused on the rapid synthesis of caffeine-catalyzed self-healable elastomer via a facile microwave-assisted synthesis route. The elastomer prepared can be used in various applications, including tactile sensors, wearable electronics, and soft robotics. SA and PEGDGE were catalyzed in the presence of caffeine under microwave irradiation followed by crosslinking in vacuo, yielding an elastomeric material. The chemical characterizations of the obtained elastomer were carried out. The resulting material is transparent, highly stretchable, and has capacitive and self-healing properties even at room temperature. The material developed can be easily applied for the aforementioned applications.

Enhancement of the Start-Up Time for Microliter-Scale Microbial Fuel Cells (µMFCs) via the Surface Modification of Gold Electrodes.

Microbial Fuel Cells (MFCs) are biological fuel cells based on the oxidation of fuels by electrogenic bacteria to generate an electric current in electrochemical cells. There are several methods that can be employed to improve their performance. In this study, the effects of gold surface modification with different thiol molecules were investigated for their implementation as anode electrodes in micro-scale MFCs (µMFCs). Several double-chamber µMFCs with 10.4 µL anode and cathode chambers were fabricated using silicon-microelectromechanical systems (MEMS) fabrication technology. µMFC systems assembled with modified gold anodes were operated under anaerobic conditions with the continuous feeding of anolyte and catholyte to compare the effect of different thiol molecules on the biofilm formation of Shewanella oneidensis MR-1. Performances were evaluated using polarization curves, Electrochemical Impedance Spectroscopy (EIS), and Scanning Electron Microcopy (SEM). The results showed that µMFCs modified with thiol self-assembled monolayers (SAMs) (cysteamine and 11-MUA) resulted in more than a 50% reduction in start-up times due to better bacterial attachment on the anode surface. Both 11-MUA and cysteamine modifications resulted in dense biofilms, as observed in SEM images. The power output was found to be similar in cysteamine-modified and bare gold µMFCs. The power and current densities obtained in this study were comparable to those reported in similar studies in the literature.

Study on Cost-Efficient Carbon Aerogel to Remove Antibiotics from Water Resources.

Because of pharmaceutical-emerging contaminants in water resources, there has been a significant increase in the antibiotic resistance in bacteria. Therefore, the removal of antibiotics from water resources is essential. Various antibiotics have been greatly studied using many different carbon-based materials including graphene-based hydrogels and aerogels. In this study, carbon aerogels (CAs) were synthesized from waste paper sources and their adsorption behaviors toward three antibiotics (hygromycin B, gentamicin, and vancomycin) were investigated, for which there exist a limited number of reports in the literature. The prepared CAs were characterized with scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and micro-computerized tomography (µ-CT). According to the µ-CT results, total porosity and open porosity were calculated as 90.80 and 90.76%, respectively. The surface area and surface-to-volume ratio were found as 795.15 mm2 and 16.79 mm-1, respectively. The specific surface area of the CAs was found as 104.2 m2/g. A detailed adsorption study was carried out based on different pH values, times, and analyte concentrations. The adsorption capacities were found as 104.16, 81.30, and 107.52 mg/g for Hyg B, Gen, and Van, respectively. For all three antibiotics, the adsorption behavior fits the Langmuir model. The kinetic studies showed that the system fits the pseudo-second-order kinetic model. The production of CAs, within the scope of this study, is safe, facile, and cost-efficient, which makes these green adsorbents a good candidate for the removal of antibiotics from water resources. This study represents the first antibiotic adsorption study based on CAs obtained from waste paper.

A comparative study on EpCAM antibody immobilization on gold surfaces and microfluidic channels for the detection of circulating tumor cells.

Detection of circulating tumor cells (CTCs) from the bloodstream holds great importance to diagnose cancer at early stages. However, CTCs being extremely rare in blood makes them difficult to reach. In this paper, we introduced different surface modification techniques for the enrichment and detection of MCF-7 in microfluidic biosensor applications using gold surface and EpCAM antibody. Mainly, two different mechanisms were employed to immobilize the antibodies; covalent bonding and bioaffinity interaction. Self-assembled monolayers (SAMs) formed on the gold surfaces were treated further for the immobilization of the antibody. The bioaffinity-based studies were performed with streptavidin and biotinylated EpCAM over the SAM coated surfaces. The cell attachment events were monitored using fluorescent microscope. Comparisons were made considering the length and functional end of alkanethiols and the positioning of the antibody. Then, these methods were integrated into a microfluidic channel system. Surface characterizations were performed with X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and contact angle measurements. The selectivity studies were carried out with EpCAM negative K562 leukaemia cell lines and the experiments were repeated for different types of surfaces, such as glass and polymer. Studies showed that long (n>10) and aromatic ring containing alkanethiols lead to better cell capture events compared to shorter ones. Results obtained from the comparisons are of importance for the gold surface-based microfluidic biosensor designs aimed for CTC detection.

Molecularly imprinted polymer based micromechanical cantilever sensor system for the selective determination of ciprofloxacin.

The main objective of this study is to develop molecularly imprinted polymer (MIP) based micromechanical cantilever sensor system that has high specificity, fast response time and is easily applicable by user for the detection of ciprofloxacin (CPX) molecule in water resources. Highly specific CPX imprinted nanoparticles were synthesized by miniemulsion polymerization technique. The average size of the synthesized nanoparticles was measured about 160nm with high monodispersivity. Covalent and monolayer binding of the MIP nanoparticles on cantilevers was provided by EDC/NHS activation. Validation of the developed cantilever nanosensor was performed in air with dip-and-dry technique by employing the dynamic sensing mode. According to the results obtained, micromechanical cantilever sensor system worked linearly for the concentration range of 1.5-150.9µM. This concentration range resulted with 18.4-48.9pg mass load on the MIP modified cantilever. The sensitivity of the developed sensor was calculated as 2.6Hz/pg. To control the specificity of MIPs, a different antibiotic enrofloxacin (ENF), with a similar physical and chemical structure with CPX, was used, which showed 7 folds low binding affinity. The developed highly specific microcantilever sensor has a response time of approximately 2min and is reusable up to 4 times. The results indicate that the MIP based AFM nanosensor has high sensitivity for the CPX molecule. This combination of MIP nanoparticles with micromechanical sensors is one of the pioneer studies in the mass sensing applications. This fast, low cost and highly sensitive CPX specific MIP nanoparticle based nanosensor developed in this research have the potential to pave the way for further studies.