Versatile conductometric biosensors for rapid and selective detection of inflammatory and cardiac biomarkers in saliva.

Biosensors have become promising alternatives to the conventional methods in early identification of diseases. However, translation of biosensors from lab to commercial products have challenges such as complex sensor fabrications and complicated detection, and inadequate sensitivity and selectivity. Here, we introduce simple and low-cost fabricated conductometric sensors based on high resistivity silicon wafers (HR-Si) which can be adopted to functionalise with both natural and synthetic antibodies in detecting five biomarkers including interleukin-6, C reactive protein, cardiac troponin I, brain natriuretic peptide, and N terminal-probrain natriuretic peptide. All five biomarkers show selective and rapid (10 min sample incubation and <1 min of reading time) detection in both media of phosphate buffer saline and saliva with the detection limits lower than that of reported healthy levels in saliva. This work highlights the versatility of HR-Si sensors in functionalisation of both natural and synthetic antibodies in sensitive and selective biomarker detection. As these miniaturised conductometric biosensors can be easily modified with on-demand biomaterials to detect corresponding target biomarkers, they enable a new category of compact point-of-care medical devices.

Rapid Conductometric Detection of SARS-CoV-2 Proteins and Its Variants Using Molecularly Imprinted Polymer Nanoparticles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biosensors have captured more attention than the conventional methodologies for SARS-CoV-2 detection due to having cost-effective platforms and fast detection. However, these reported SARS-CoV-2 biosensors suffer from drawbacks including issues in detection sensitivity, degradation of biomaterials on the sensor's surface, and incapability to reuse the biosensors. To overcome these shortcomings, molecularly imprinted polymer nanoparticles (nanoMIPs) incorporated conductometric biosensor for highly accurate, rapid, and selective detection of two model SARS-CoV-2 proteins: (i) receptor binding domain (RBD) of the spike (S) glycoprotein and (ii) full length trimeric spike protein are introduced. In addition, these biosensors successfully responded to several other SARS-CoV-2 RBD spike protein variants including Alpha, Beta, Gamma, and Delta. Our conductometric biosensor selectively detects the two model proteins and SARS-CoV-2 RBD spike protein variant samples in real-time with sensitivity to a detection limit of 7 pg mL-1 within 10 min of sample incubation. A battery-free, wireless near-field communication (NFC) interface is incorporated with the biosensor for fast and contactless detection of SARS-CoV-2 variants. The smartphone enabled real-time detection and on-screen rapid result for SARS-CoV-2 variants can curve the outbreak due to its ability to alert the user to infection in real time.

Rapid and Selective Biomarker Detection with Conductometric Sensors.

The biomarker detection in human body fluids is crucial as biomarkers are important in diagnosing diseases. Conventional invasive techniques for biomarker detection are associated with infection, tissue damage, and discomfort. Non-invasive devices are an attractive alternative. Here, metal oxide (oxygen-deficient zinc oxide, ZnO) based conductometric sensors with two-terminal electrodes for rapid detection of biomarkers in real-time, are presented. This platform can be engineered for non-invasive, sensitive, and on-demand selective detection of biomarkers based on surface functionalization. The three novelties in this biosensing technique include an on-demand target selection device platform, short (<10 min) incubation times, and real-time monitoring of the biomarker of interest by electrical (resistance change) measurements. Cardiac inflammatory biomarkers interleukin 6 (IL-6) and C-reactive protein (CRP) are used as the model antigens. The devices can detect 100× lower concentration of IL-6 than healthy levels in human saliva and sweat and 1000× and ≈50× lower CRP concentrations than healthy levels in human saliva and sweat, respectively. The devices show high selectivity for IL-6 and CRP antigens when tested with a mixture of biomarkers. This sensor platform can be extended to selective measurements for viruses or DNA screening, which enables a new category of compact and rapid point-of-care medical devices.

Facile displacement of citrate residues from gold nanoparticle surfaces.

The stability of citrate-residues on gold nanoparticles (AuNPs) against ligand displacement has been controversial. Using AuNPs synthesized with deuterated citrate in combination with in-situ surface-enhanced Raman spectroscopic (SERS) analysis, we report that both citrate-residues and solution impurities can be simultaneously adsorbed onto citrate-reduced AuNPs in solution. The citrate-residues can be readily displaced from AuNPs by organosulfur such as organothiols (RS-H), organodisuflide (R-S-S-R), and non-specific ligands including halides and adenine. Control experiments conducted on high-purity gold films sputter-coated onto silicone substrates indicate that air-borne and solvent-borne impurities rapidly contaminate the gold surfaces. Head-to-head comparison of ligand-functionalized AuNPs by in-situ SERS measurements verses those from the ex-situ X-ray photoelectron spectroscopic (XPS) measurements reveal that the impurity deposition can compromise the reliability of ex-situ XPS identification of surface adsorbates on AuNPs in solution. These insights are of general significance to nanoscience research given the broad interest in nanoparticle surface chemistry and popularity of XPS for nanomaterial characterizations.

Direct Observation of Ion Pairing at the Liquid/Solid Interfaces by Surface Enhanced Raman Spectroscopy.

Ion-pairing, the association of oppositely charged ionic species in solution and at liquid/solid interfaces has been proposed as a key factor for a wide range of physicochemical phenomena. However, experimental observations of ion pairing at the ligand/solid interfaces are challenging due to difficulties in differentiating ion species in the electrical double layer from that adsorbed on the solid surfaces. Using surface enhanced Raman spectroscopy in combination with electrolyte washing, we presented herein the first direct experimental evidence of ion pairing, the coadsorption of oppositely charged ionic species onto gold nanoparticles (AuNPs). Ion pairing reduces the electrolyte concentration threshold in inducing AuNP aggregation and enhances the competitiveness of electrolyte over neutral molecules for binding to AuNP surfaces. The methodology and insights provided in this work should be important for understanding electrolyte interfacial interactions with nanoparticles.