Application of CRISPR Cas Systems for Biosensing.

The essential properties of a biosensor are its sensitivity and selectivity to detect, monitor and quantify the biomarker(s) for the interests of medicine [...

Design and Application of Metal Organic Framework ZIF-90-ZnO-MoS Nanohybrid for an Integrated Electrochemical Liquid Biopsy.

Limited healthcare capacity highlights the needs of integrated sensing systems for personalized health-monitoring. However, only limited sensors can be employed for point-of-care applications, emphasizing the lack of a generalizable sensing platform. Here, we report a metal organic framework (MOF) ZIF-90-ZnO-MoS nanohybrid-based integrated electrochemical liquid biopsy (ELB) platform capable of direct profiling cancer exosomes from blood.

An Integrated Multi-Function Heterogeneous Biochemical Circuit for High-Resolution Electrochemistry-Based Genetic Analysis.

Modular construction of an autonomous and programmable multi-functional heterogeneous biochemical circuit that can identify, transform, translate, and amplify biological signals into physicochemical signals based on logic design principles can be a powerful means for the development of a variety of biotechnologies. To explore the conceptual validity, we design a CRISPR-array-mediated primer-exchange-reaction-based biochemical circuit cascade, which probes a specific biomolecular input, transform the input into a structurally accessible form for circuit wiring, translate the input information into an arbitrary sequence, and finally amplify the prescribed sequence through autonomous formation of a signaling concatemer. This upstream biochemical circuit is further wired with a downstream electrochemical interface, delivering an integrated bioanalytical platform.

Phase-Regulated Sensing Mechanism of MoS Based Nanohybrids toward Point-of-Care Prostate Cancer Diagnosis.

Alpha-methylacyl-CoA racemase (AMACR) has been proven to be consistently overexpressed in prostate cancer epitheliums, and is expected to act as a positive biomarker for the diagnosis of prostate carcinoma in clinical practice. Here, a strategy for specific determination of AMACR in real human serum by using an electrochemical microsensor system is presented. In order to implement the protocol, a self-organized nanohybrid consisting of metal nanopillars in a 2D MoS matrix is developed as material for the sensing interface.

Surpassing the detection limit and accuracy of the electrochemical DNA sensor through the application of CRISPR Cas systems.

Robust developments of personalized medicine for next-generation healthcare highlight the need for sensitive and accurate point-of-care platforms for quantification of disease biomarkers. Broad presentations of clustered regularly interspaced short palindromic repeats (CRISPR) as an accurate gene editing tool also indicate that the high-specificity and programmability of CRISPR system can be utilized for the development of biosensing systems. Herein, we present a CRISPR Cas system enhanced electrochemical DNA (E-DNA) sensor with unprecedented sensitivity and accuracy.

Recent Developments of Electrochemical and Optical Biosensors for Antibody Detection.

Detection of biomarkers has raised much interest recently due to the need for disease diagnosis and personalized medicine in future point-of-care systems. Among various biomarkers, antibodies are an important type of detection target due to their potential for indicating disease progression stage and the efficiency of therapeutic antibody drug treatment. In this review, electrochemical and optical detection of antibodies are discussed.

Immunoglobulin G-Based Steric Hindrance Assay for Protein Detection.

With the imminent needs of rapid, accurate, simple point-of-care systems for global healthcare industry, electrochemical biosensors have been widely developed owing to their cost-effectiveness and simple instrumentation. However, typical electrochemical biosensors for direct analysis of proteins in the human biological sample still suffer from complex biosensor fabrication, lack of general method, limited sensitivity, and matrix-caused biofouling effect. To resolve these challenges, we developed a general electrochemical sensing strategy based on a designed steric hindrance effect on an antibody surface layer.

Strand Displacement Strategies for Biosensor Applications.

DNA has many unique properties beyond encoding genetic information, one of which is its physicochemical stability based on Watson-Crick base pairing. Differences in sequence complementarity between multiple DNA strands can lead to the strand displacement reaction (SDR). SDRs have been regularly applied in synthetic biology, drug delivery, and, importantly, biosensing.

Exploring the Trans-Cleavage Activity of CRISPR-Cas12a (cpf1) for the Development of a Universal Electrochemical Biosensor.

An accurate, rapid, and cost-effective biosensor for the quantification of disease biomarkers is vital for the development of early-diagnostic point-of-care systems. The recent discovery of the trans-cleavage property of CRISPR type V effectors makes CRISPR a potential high-accuracy bio-recognition tool. Herein, a CRISPR-Cas12a (cpf1) based electrochemical biosensor (E-CRISPR) is reported, which is more cost-effective and portable than optical-transduction-based biosensors.

Dynamic Control of Peptide Strand Displacement Reaction Using Functional Biomolecular Domain for Biosensing.

Nature's great repository provides nucleic acids and amino acids as the fundamental elements of life. Inspired by the programmability of nucleic acids, DNA nanotechnology has been extensively developed based on the strand displacement reaction of nucleic acids. In comparison with nucleic acids, amino acids possess higher programmability and more functionalities owing to the diversity of the amino acid unit.

Detection of Phenylketonuria Markers Using a ZIF-67 Encapsulated PtPd Alloy Nanoparticle (PtPd@ZIF-67)-Based Disposable Electrochemical Microsensor.

Phenylketonuria (PKU) is a common disease in congenital disorder of amino acid metabolism, which can lead to intellectual disability, seizures, behavioral problems, and mental disorders. We report herein a facile method to screen for PKU by the measurements of its metabolites (markers). In this work, a disposable electrochemical microsensor modified with a ZIF (zeolitic imidazolate framework)-based nanocomposite is constructed, in which ZIF-67 crystals are encapsulated with PtPd alloy nanoparticles (NPs) forming the nanocomposite (PtPd@ZIF-67).

Recent Advances on Electrochemical Biosensing Strategies toward Universal Point-of-Care Systems.

A number of very recently developed electrochemical biosensing strategies are promoting electrochemical biosensing systems into practical point-of-care applications. The focus of research endeavors has transferred from detection of a specific analyte to the development of general biosensing strategies that can be applied for a single category of analytes, such as nucleic acids, proteins, and cells. In this Minireview, recent cutting-edge research on electrochemical biosensing strategies are described.

Nanoparticle based simple electrochemical biosensor platform for profiling of protein-nucleic acid interactions.

The analysis of protein-nucleic acid interactions is essential for biophysics related research. However, simple, rapid, and accurate methods for quantitative analysis of biomolecular interactions are lacking. We herein establish an electrochemical biosensor approach for protein-nucleic acid binding analysis.

Neutral Charged Immunosensor Platform for Protein-based Biomarker Analysis with Enhanced Sensitivity.

A noninvasive, highly sensitive universal immunosensor platform for protein-based biomarker detection is described in this Article. A neutral charged sensing environment is constructed by an antibody with an oppositely charged amino acid as surface charge neutralizer. By adjusting the pH condition of the testing environment, this neutral charged immunosensor (NCI) directly utilizes the electrostatic charges of the analyte for quantification of circulating protein markers, achieving a wide dynamic range covering through the whole picomole level.

Advanced fabrication of biosensor on detection of Glypican-1 using S-Acetylmercaptosuccinic anhydride (SAMSA) modification of antibody.

Glypican-1 (GPC-1) has been recognized as biomarker of pancreatic cancer. Quantification of GPC-1 level is also pivotal to breast cancer and prostate cancer's patients. We hereby report the first biosensor for GPC-1 detection.

Effect of MnO Phase Structure on the Oxidative Reactivity toward Bisphenol A Degradation.

Manganese dioxides (MnO) are among important environmental oxidants in contaminant removal; however, most existing work has only focused on naturally abundant MnO. We herein report the effects of different phase structures of synthetic MnO on their oxidative activity with regard to contaminant degradation. Bisphenol A (BPA), a frequently detected contaminant in the environment, was used as a probe compound.

Bioconjugated, Single-Use Biosensor for the Detection of Biomarkers of Prostate Cancer.

Prostate cancer is prevalent among cancers in men. A simple method for screening of reliable biomarkers is pivotal for early detection of prostate cancer.  Prostate-specific antigen (PSA) has been a commonly used biomarker for prostate cancer, in spite of its false-positive limitation.

Application of bioconjugation chemistry on biosensor fabrication for detection of TAR-DNA binding protein 43.

A simple-prepare, single-use and cost-effective, in vitro biosensor for the detection of TAR DNA-binding protein 43 (TDP-43), a biomarker of neuro-degenerative disorders, was designed, manufactured and tested. This study reports the first biosensor application for the detection of TDP-43 using a novel biosensor fabrication methodology. Bioconjugation mechanism was applied by conjugating anti-TDP 43 with N-succinimidyl S-acetylthioacetate (SATA) producing a thiol-linked anti-TDP 43, which was used to directly link with gold electrode surface, minimizing the preparation steps for biosensor fabrication and simplifying the biosensor surface.

A Cuprous Oxide Thin Film Non-Enzymatic Glucose Sensor Using Differential Pulse Voltammetry and Other Voltammetry Methods and a Comparison to Different Thin Film Electrodes on the Detection of Glucose in an Alkaline Solution.

A cuprous oxide (Cu₂O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50-200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype.

In Vitro Quantified Determination of β-Amyloid 42 Peptides, a Biomarker of Neuro-Degenerative Disorders, in PBS and Human Serum Using a Simple, Cost-Effective Thin Gold Film Biosensor.

A simple in vitro biosensor for the detection of β-amyloid 42 in phosphate-buffered saline (PBS) and undiluted human serum was fabricated and tested based on our platform sensor technology. The bio-recognition mechanism of this biosensor was based on the effect of the interaction between antibody and antigen of β-amyloid 42 to the redox couple probe of K₄Fe(CN)₆ and K₃Fe(CN)₆. Differential pulse voltammetry (DPV) served as the transduction mechanism measuring the current output derived from the redox coupling reaction.

A Simple, Cost-Effective Sensor for Detecting Lead Ions in Water Using Under-Potential Deposited Bismuth Sub-Layer with Differential Pulse Voltammetry (DPV).

This research has developed a simple to use, cost effective sensor system for the detection of lead ions in tap water. An under-potential deposited bismuth sub-layer on a thin gold film based electrochemical sensor was designed, manufactured, and evaluated. Differential pulse voltammetry (DPV) measurement technique was employed in this detection.

Detection of 17 β-Estradiol in Environmental Samples and for Health Care Using a Single-Use, Cost-Effective Biosensor Based on Differential Pulse Voltammetry (DPV).

Environmental estrogen pollution and estrogen effects on the female reproductive system are well recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproductive system. 17 β-estradiol is carcinogenic and has a tumor promotion effect relating to breast cancer, lung cancer and others.

A Single-Use, In Vitro Biosensor for the Detection of T-Tau Protein, A Biomarker of Neuro-Degenerative Disorders, in PBS and Human Serum Using Differential Pulse Voltammetry (DPV).

A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet.

Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV).

A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor.

Pt35Cu65 nanoarchitecture: a highly durable and effective electrocatalyst towards methanol oxidation.

Aiming at electro-catalytic performance enhancement and reduction of catalyst cost, PtxCu1-x (Pt35Cu65, Pt53Cu47, and Pt68Cu32) nanoarchitecture samples with controllable atomic composition, similar morphology and particle-size have been prepared by using a one-pot chemical route. The as-prepared PtxCu1-x nanoarchitectures are confirmed as consisting of the integration of initial small alloy nanoparticles (NPs), resulting in an interconnected nanoporous structure. The electrochemical experiments indicate that these PtxCu1-x nanocatalysts exhibit atomic composition dependent catalytic activity, although the surfaces of all the catalysts were characterized to be featured with a Pt enrichment structure.