An electrochemical device to control sample pH locally in Lab-on-PCB devices: an investigation into spatial resolution.

During the recent pandemic outbreak, Lab-on-Chip devices did not manage to fully reach their potential in rapid diagnosis of pathogens, mainly due to the lack of cost-effective LoC solutions integrated with all required sample preparation modules. This paper presents such a critical step, aiming to translate electrochemical pH control into practical protein preconcentration modules, easy to integrate with subsequent quantification modules seamlessly via Lab-on-PCB technology. In this work we present a device capable of electrochemically controlling the pH of a solution local to an individually addressed electrode in a PCB array. The electrodes were functionalised with an electropolymerised self-assembled monolayer of 4-Aminothiophenol and were subjected to voltages of 0.2–0.4 V, evaluating for the first time the bias effect both over time and over space. This study enables for the first time the implementation of this technique for electrochemical pH control into practical Lab-on-PCB devices such as isoelectric focusing, via the informed design of such electrode arrays of appropriate size and spacing

Printable graphene BioFETs for DNA quantification in Lab-on-PCB microsystems

Lab-on-Chip is a technology that aims to transform the Point-of-Care (PoC) diagnostics field; nonetheless a commercial production compatible technology isyet to be established. Lab-on-Printed Circuit Board (Lab-on-PCB) is currentlyconsidered as a promising candidate technology for cost-aware butsimultaneously high specification applications, requiring multi-componentmicrosystem implementations, due to its inherent compatibility with electronicsand the long-standing industrial manufacturing basis. In this work, wedemonstrate the first electrolyte gated field-effect transistor (FET) DNAbiosensor implemented on commercially fabricated PCB in a planar layout.Graphene ink was drop-casted to form the transistor channel and PNA probeswere immobilized on the graphene channel, enabling label-free DNA detection. Itis shown that the sensor can selectively detect the complementary DNAsequence, following a fully inkjet-printing compatible manufacturing process. The results demonstrate the potential for the effortless integration of FET sensorsinto Lab-on-PCB diagnostic platforms, paving the way for even higher sensitivityquantification than the current Lab-on-PCB state-of-the-art of passive electrodeelectrochemical sensing. The substitution of such biosensors with our presentedFET structures, promises further reduction of the time-to-result in microsystemscombining sequential DNA amplification and detection modules to few minutes,since much fewer amplification cycles are required even for low-abundancenucleic acid targets

Multiplexed prostate cancer companion diagnostic devices

Prostate cancer (PCa) remains one of the most prominent forms of cancer for men. Since the early 1990s, Prostate-Specific Antigen (PSA) has been a commonly recognized PCa-associated protein biomarker. However, PSA testing has been shown to lack in specificity and sensitivity when needed to diagnose, monitor and/or treat PCa patients successfully. One enhancement could include the simultaneous detection of multiple PCa-associated protein biomarkers alongside PSA, also known as multiplexing. If conventional methods such as the enzyme-linked immunosorbent assay (ELISA) are used, multiplexed detection of such protein biomarkers can result in an increase in the required sample volume, in the complexity of the analytical procedures, and in adding to the cost. Using companion diagnostic devices such as biosensors, which can be portable and cost-effective with multiplexing capacities, may address these limitations. This review explores recent research for multiplexed PCa protein biomarker detection using optical and electrochemical biosensor platforms. Some of the novel and potential serum-based PCa protein biomarkers will be discussed in this review. In addition, this review discusses the importance of converting research protocols into multiplex point-of-care testing (xPOCT) devices to be used in near-patient settings, providing a more personalized approach to PCa patients’ diagnostic, surveillance and treatment management

Utilizing Commercially Fabricated Printed Circuit Boards as an Electrochemical Biosensing Platform

Printed circuit boards (PCBs) offer a promising platform for the development of electronics-assisted biomedical diagnostic sensors and microsystems. The long-standing industrial basis offers distinctive advantages for cost-effective, reproducible, and easily integrated sample-in-answer-out diagnostic microsystems. Nonetheless, the commercial techniques used in the fabrication of PCBs produce various contaminants potentially degrading severely their stability and repeatability in electrochemical sensing applications. Herein, we analyse for the first time such critical technological considerations, allowing the exploitation of commercial PCB platforms as reliable electrochemical sensing platforms. The presented electrochemical and physical characterisation data reveal clear evidence of both organic and inorganic sensing electrode surface contaminants, which can be removed using various pre-cleaning techniques. We demonstrate that, following such pre-treatment rules, PCB-based electrodes can be reliably fabricated for sensitive electrochemical biosensors. Herein, we demonstrate the applicability of the methodology both for labelled protein (procalcitonin) and label-free nucleic acid (E. coli-specific DNA) biomarker quantification, with observed limits of detection (LoD) of 2 pM and 110 pM, respectively. The proposed optimisation of surface pre-treatment is critical in the development of robust and sensitive PCB-based electrochemical sensors for both clinical and environmental diagnostics and monitoring applications

Electrochemical Sensors Based on Metal Nanoparticles with Biocatalytic Activity

Biosensors have attracted a great deal of attention, as they allow for the translation of the standard laboratory-based methods into small, portable devices. The field of biosensors has been growing, introducing innovations into their design to improve their sensing characteristics and reduce sample volume and user intervention. Enzymes are commonly used for determination purposes providing a high selectivity and sensitivity; however, their poor shelf-life is a limiting factor. Researchers have been studying the possibility of substituting enzymes with other materials with an enzyme-like activity and improved long-term stability and suitability for point-of-care biosensors. Extra attention is paid to metal and metal oxide nanoparticles, which are essential components of numerous enzyme-less catalytic sensors. The bottleneck of utilising metal-containing nanoparticles in sensing devices is achieving high selectivity and sensitivity. This review demonstrates similarities and differences between numerous metal nanoparticle-based sensors described in the literature to pinpoint the crucial factors determining their catalytic performance. Unlike other reviews, sensors are categorised by the type of metal to study their catalytic activity dependency on the environmental conditions. The results are based on studies on nanoparticle properties to narrow the gap between fundamental and applied research. The analysis shows that the catalytic activity of nanozymes is strongly dependent on their intrinsic properties (e.g. composition, size, shape) and external conditions (e.g. pH, type of electrolyte, and its chemical composition). Understanding the mechanisms behind the metal catalytic activity and how it can be improved helps designing a nanozyme-based sensor with the performance matching those of an enzyme-based device. GRAPHICAL ABSTRACT: [Image: see text

Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

Affinity-based electrochemical (EC) sensors offer a potentially valuable approach for point-of-care (POC) diagnostics applications, and for the detection of diseases, such as sepsis, that require simultaneous detection of multiple biomarkers, but their development has been hampered due to biological fouling and EC noise. Here, an EC sensor platform that enables detection of multiple sepsis biomarkers simultaneously by incorporating a nanocomposite coating composed of crosslinked bovine serum albumin containing a network of reduced graphene oxide nanoparticles that prevents biofouling while maintaining electroconductivity is described. Using nanocomposite coated planar gold electrodes, a sensitive procalcitonin (PCT) sensor is constructed and validated in undiluted serum, which produced an excellent correlation with a conventional ELISA (adjusted r 2 = 0.95) using clinical samples. A single multiplexed platform containing sensors for three different sepsis biomarkers—PCT, C-reactive protein, and pathogen-associated molecular patterns—is also developed, which exhibits specific responses within the clinically significant range without any cross-reactivity. This platform enables sensitive simultaneous EC detection of multiple analytes in human whole blood, and it can be applied to detect any target analyte with an appropriate antibody pair. Thus, this nanocomposite-enabled EC sensor platform may offer a potentially valuable tool for development of a wide range of clinical POC diagnostics.</p

Commercially Fabricated Printed Circuit Board Sensing Electrodes for Biomarker Electrochemical Detection: The Importance of Electrode Surface Characteristics in Sensor Performance

Here we report the first PCB-implemented electrochemical glucose biosensor usingcovalently immobilized glucose oxidase (GOx) on the commercially fabricated PCB electrodesurface, taking particular care on the electrode surface characteristics and their effect on sensorperformance. Based on the results, this assay exhibits a highly linear response from 500 &#956;M to 20mM (R = 0.9961) and a lower limit of detection of 500 &#956;M