A review of microfabricated electrochemical biosensors for DNA detection

This review article presents an overview of recent work on electrochemical biosensors developed using microfabrication processes, particularly sensors used to achieve sensitive and specific detection of DNA sequences. Such devices are important as they lend themselves to miniaturisation, reproducible mass-manufacture, and integration with other previously existing technologies and production methods. The review describes the current state of these biosensors, novel methods used to produce them or enhance their sensing properties, and pathways to deployment of a complete point-of-care biosensing system in a clinical setting

Developments in microscale and nanoscale sensors for biomedical sensing

The widespread use of point of care testing in biomedical and clinical applications is a major aim of the electrochemical field. A large number of groups are working on lab-on-a-chip systems or sensor arrays which are underpinned by electrochemical detection methodologies. Miniaturized transducers have the potential to be adopted in such systems for diagnosis of a range of diseases in both clinical and nonclinical settings. In this review, we will present the current trends and state of the art for a selection of miniaturized sensing elements (microelectrodes, nanoelectrodes, and field-effect transistors) and provide an impression of current technologies, their associated performance characteristics, and also considering the major barriers to adoption and how they might be surmounted in future so these technologies can fulfil their early promise

Developing a low-cost, simple-to-use electrochemical sensor for the detection of circulating tumour DNA in human fluids

It is well-known that two major issues, preventing improved outcomes from cancer are late diagnosis and the evolution of drug resistance during chemotherapy, therefore technologies that address these issues can have a transformative effect on healthcare workflows. In this work we present a simple, low-cost DNA biosensor that was developed specifically to detect mutations in a key oncogene (KRAS). The sensor employed was a screen-printed array of carbon electrodes, used to perform parallel measurements of DNA hybridisation. A DNA amplification reaction was developed with primers for mutant and wild type KRAS sequences which amplified target sequences from representative clinical samples to detectable levels in as few as twenty cycles. High levels of sensitivity were demonstrated alongside a clear exemplar of assay specificity by showing the mutant KRAS sequence was detectable against a significant background of wild type DNA following amplification and hybridisation on the sensor surface. The time to result was found to be 3.5 h with considerable potential for optimisation through assay integration. This quick and versatile biosensor has the potential to be deployed in a low-cost, point-of-care test where patients can be screened either for early diagnosis purposes or monitoring of response to therapy

Development of a rapid, antimicrobial susceptibility test for E. coli based on low-cost, screen-printed electrodes

Antibiotic resistance has been cited by the World Health Organisation (WHO) as one of the greatest threats to public health. Mitigating the spread of antibiotic resistance requires a multipronged approach with possible interventions including faster diagnostic testing and enhanced antibiotic stewardship. This study employs a low-cost diagnostic sensor test to rapidly pinpoint the correct antibiotic for treatment of infection. The sensor comprises a screen-printed gold electrode, modified with an antibiotic-seeded hydrogel to monitor bacterial growth. Electrochemical growth profiles of the common microorganism, Escherichia coli (E. coli) (ATCC 25922) were measured in the presence and absence of the antibiotic streptomycin. Results show a clear distinction between the E. coli growth profiles depending on whether streptomycin is present, in a timeframe of ≈2.5 h (p < 0.05), significantly quicker than the current gold standard of culture-based antimicrobial susceptibility testing. These results demonstrate a clear pathway to a low cost, phenotypic and reproducible antibiotic susceptibility testing technology for the rapid detection of E. coli within clinically relevant concentration ranges for conditions such as urinary tract infections

Test Structures for Developing Packaging for Implantable Sensors

With their capacity for real time monitoring and spatial mapping, implantable sensors are becoming an increasingly important aspect of next generation precision healthcare. Microfabricated sensor systems are a popular choice, owing to their capacity for miniaturisation, repeatable mass manufacture, and numerous pre-existing sensor archetypes. Despite the drive for development, packaging these sensors for the environment within the body, as well as the implantation process itself, presents a significant challenge. This paper presents microelectronic test structures, which can be used to assess, compare, and optimise implantable packaging solutions in a standardised manner. The proposed structures are used to investigate: (i) the capacity of the material to be patterned, (ii) the permeability of the insulation material, (iii) adhesion of the encapsulant to the die, and (iv) the physical robustness of the package to implantation through a needle. They are used to characterise an example packaging strategy, using biocompatible epoxy-resin. In addition, a method of optimising the packaging performance using the test structures is presented

A Low Cost Patternable Packaging Technology for Biosensors

This paper demonstrates a simple and low cost technology to reliably and accurately package integrated chips. Microchannels and cavities of minimum feature size of 500 μm can be reliably reproduced. In addition, the curing depth in relation to the exposure time was investigated. A simple microfluidic device, consisting of a 500 μm channel and 2 mm ports, was manufactured to demonstrate the possibilities of this technology. Extensive electrochemical experiments showed that the packaging material is a good insulator and leaves no residue on the chip

Improving the yield and lifetime of microfabricated sensors for harsh environments

This paper details improvements in the design and fabrication of electrodes intended to function in the high temperature, corrosive environment of a molten salt. Previously reported devices have displayed low yield and lifetimes and this paper presents two strategies to improve these aspects of their performance. The first one involves reducing the critical area, which increased both the electrode yield and lifetimes. The second element utilised test structures, targeted at identifying failure mechanisms, which helped facilitate the materials/design modifications required to make the devices more robust

Biologically modified microelectrode sensors provide enhanced sensitivity for detection of nucleic acid sequences from Mycobacterium tuberculosis

This paper describes improved sensitivity when using biosensors based on microfabricated microelectrodes to detect DNA, with the goal of progressing towards a low cost and mass manufacturable assay for antibiotic resistance in tuberculosis (TB). The microelectrodes gave a near 20 times improvement in sensitivity compared to polycrystalline macroelectrodes. In addition, experimental parameters such as redox mediator concentration and experimental technique were investigated and optimised. It was found that lower concentrations of redox mediator gave higher signal changes when measuring hybridisation events and, at these lower concentrations, square wave voltammetry was more sensitive and consistent than differential pulse voltammetry. Together, this paper presents a quantifiable comparison of macroelectrode and microelectrode DNA biosensors. The final assay demonstrates enhanced sensitivity through reduction of sensor size, reduction of redox mediator concentration and judicious choice of detection technique, therefore maintaining manufacturability for incorporation into point of care tests and lab-on-a-chip devices

Comparison of Conventional and Maskless Lithographic Techniques for More than Moore Post-processing of Foundry CMOS Chips

This article details and compares the technology options for post-processing foundry produced CMOS at chip-scale to enable More than Moore functionality. In many cases there are attractions in using chip-based processing through the Multi-Project Wafer route that is frequently employed in research, early-stage development and low-volume production. This article identifies that spray-based photoresist deposition combined with optical maskless lithography demonstrates sufficient performance combined with low cost and operational convenience to offer an attractive alternative to conventional optical lithography, where spin-coated photoresist is exposed through a patterned photomask. [2020-0249