Paper-based sensors offer an affordable yet powerful platform for field and point-of-care (POC) testing due to their self-pumping ability and utility for many different analytical measurements. When combined with electrochemical detection using small and portable electronics, sensitivity and selectivity of the paper devices can be improved over naked eye detection without sacrificing portability. Herein, we review how the field of electrochemical paper-based analytical devices (ePADs) has grown since it was introduced a decade ago. We start by reviewing fabrication methods relevant to ePADs with more focus given to the electrode fabrication, which is fundamental for electrochemical sensing. Multiple sensing approaches applicable to ePADs are then discussed and evaluated to present applicability, advantages and challenges associated with each approach. Recent applications of ePADs in the fields of clinical diagnostics, environmental testing, and food analysis are also presented. Finally, we discuss how the current ePAD technologies have progressed to meet the analytical and practical specifications required for field and/or POC applications, as well as challenges and outlook.

Electrochemical paper-based devices: sensing approaches and progress toward practical applications

Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.

Applications of Catalytic Hairpin Assembly Reaction in Biosensing.

https://iopscience.iop.org/article/10.1149/2.0171912jes/pdf

Review—Recent Developments on Graphene-Based Electrochemical Sensors toward Nitrite

In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing.

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Nanomaterials for Healthcare Biosensing Applications

Aptasensors as the future of antibiotics test kits-a case study of the aptamer application in the chloramphenicol detection

Development of a paper-based, inexpensive, and disposable electrochemical sensing platform for nitrite detection

Graphite-like carbon nitride (g-C3N4) nanosheet is a new type of photoactive semiconducting material with promising application in photoelectrochemical (PEC) biosensor. In the present work, a simple and selective PEC biosensor was fabricated using g-C3N4 nanosheets as photoactive material coupled with capture-release strategy. DNA aptamer labeled with ferrocene (DNA-Fc) was served as both recognition reagent of antibiotic chloramphenicol and electron donor of PEC biosensor. Based on the decreased affinity of aptamer to g-C3N4 nanosheets causing by the formation of aptamer-chloramphenicol complex, DNA-Fc could be released from g-C3N4 nanosheets modified ITO surface, resulting a decreased PEC response. The developed method showed a wide linear range from 1 pM to 100 nM and a low detection limit of 0.22 pM (3σ). The fabricated PEC biosensor also illustrated good detection specificity and can be applied to detect chloramphenicol residue in water samples with recoveries ranging from 94.5% to 107.3%.

Aptamer-based photoelectrochemical biosensor for antibiotic detection using ferrocene modified DNA as both aptamer and electron donor

Signal-on electrochemical detection of DNA methylation based on the target-induced conformational change of a DNA probe and exonuclease III-assisted target recycling.

A highly sensitive and selective biosensing system was designed to analyze DNA methylation using a dual-signal readout technique in combination with the signal amplification of supersandwich DNA structure. Through the ingenious design of target-triggered cascade of hybridization chain reaction, one target DNA could initiate the formation of supersandwich structure with multiple signal probes. As a result, one-to-multiple amplification effect was achieved, which conferred high sensitivity to target molecular recognition. Based on probe 1 labeled with ferrocene and probe 2 modified with methylene blue, the target DNA was clearly recognized by two electrochemical signals at independent potentials, which was helpful for the acquisition of more accurate detection results. Taking advantage of bisulfite conversion, the methylation status of cytosine (C) was changed to nucleic acid sequence status, which facilitated the hybridization-based detection without enzymatic reaction. Consequently, the methylated DNA was detected at the femtomolar level with satisfactory analytical parameters. The proposed system was effectively used to assess methylated DNA in human blood serum samples, illuminating the possibility of the sensing platform for applications in disease diagnosis and biochemistry research.

Dual-Signal Readout of DNA Methylation Status Based on the Assembly of a Supersandwich Electrochemical Biosensor without Enzymatic Reaction

The cytosines in cluster-nucleation sequences play a vital role in the formation of silver nanoclusters (Ag NCs). Here, an innovative electrochemiluminescence (ECL) resonance energy transfer (RET) sensing system was developed using CdS quantum dots (QDs) as ECL donor and Ag NCs as ECL acceptor. Modulation of the number of cytosines in the cluster-nucleation sequences allowed tuning of Ag NCs absorption bands to match with the ECL emission spectrum of CdS QDs, yielding effective ECL-RET. The sensitivity of detection was improved by dual-target recycling amplification based on duplex-specific nuclease (DSN) and catalytic hairpin assembly. In the presence of target microRNA-21 (miRNA-21), DSN selectively cleaved the complementary DNA section (S1), resulting in the release of the transduction section (S2) and the reuse of miRNA-21 in the next recycling amplification. Interaction of the stem-loop structure of the DNA1 segment (H1) on CdS QDs-modified electrode with S2 led to the opening of the hairpin structure of H1 and the formation of H1:S2 duplex. Then, hairpin DNA2 encapsulated Ag NCs hybridized with the remaining single-stranded DNA segment of H1, and the S2 strand was replaced. Finally, the dissociated S2 participated in subsequent reaction cycles, introducing Ag NCs to the electrode surface and leading to ECL signal quenching of the CdS QDs. The proposed sensor showed excellent performance in detecting miRNA-21 at a wide linear range from 1 fM to 100 pM. The practical application ability of the strategy was tested in HeLa cells with acceptable results, suggesting that the detection platform is a promising approach for disease diagnosis and molecular biology research.

Mengying Wang

Papers

Development of a paper-based, inexpensive, and disposable electrochemical sensing platform for nitrite detection

Aptamer-based photoelectrochemical biosensor for antibiotic detection using ferrocene modified DNA as both aptamer and electron donor

Signal-on electrochemical detection of DNA methylation based on the target-induced conformational change of a DNA probe and exonuclease III-assisted target recycling.

Dual-Signal Readout of DNA Methylation Status Based on the Assembly of a Supersandwich Electrochemical Biosensor without Enzymatic Reaction

Construction of a Cytosine-Adjusted Electrochemiluminescence Resonance Energy Transfer System for MicroRNA Detection.