Field-Effect Devices (FEDs): Detection of Charged Macromolecules, Direct Electrostatic DNA Detection and Microfluidic Modules

Abstract

In order to provide an accurate diagnosis of many different medical issues, sensitive and precise detection of DNA biomarkers is essential. The requirement to apply an extra labelling step to the device frequently complicates the adoption of such biosensing components in integrated microfluidic devices. We highlighted recent developments in microfluidic integrated devices as a means of presenting label-free DNA biosensor technology in this review. The literature began with examples of basic biosensing methods implemented in flow-cell structures, then moved on to more complex microfluidic devices, and finally, instances of higher integration. The use of nanopore technology to sequence complete genomes on microfluidic chips was emphasised, as were recent advances in the commercialisation of label-free DNA detection devices on microfluidic chips. The technical viability of future high-throughput and high-specification portable systems is clearly demonstrated by multiplexed DNA amplification modules, droplet-based microfluidics, and nanopore-assisted sequencing. At present, nanopore technology allows for point-of-need DNA sequencing with a throughput of 10–20 G bases per 48 hours. While this kind of sequencing throughput is certainly remarkable, there are many diagnostic uses for which whole genome sequencing is superfluous. For both Point-of-Need applications in centralised healthcare systems and low-resource settings, microfluidic technologies that provide sample-in-answer-out operations with a few minute time to result may be more realistic in real-life practice. Several commercial initiatives are now showing signs of imminently launching sample-in-answer-out systems with targeted medical diagnostic applications, building on more established technologies in microfluidic DNA systems. Integrating very sensitive biosensors into portable devices, or even systems that do not require any equipment, at a reasonable cost is a significant obstacle that needs to be addressed. Due to the fact that different diagnostic companies are following different strategies, there is currently no commercially available method for mass-producing a product that seamlessly integrates all of the necessary components. In addition to the high power demands of heating on modules that incorporate DNA amplification, the use of sensing technologies that necessitate complex or costly equipment can provide challenges in terms of portability. There is a pressing need to create assays and devices that enable multiplexed detection since most real-world applications require the simultaneous quantification of multiple DNA strands. In conclusion, it is essential to conduct early device development using real physiological samples in order to guarantee device compliance with biomedical device standards and worldwide regulatory frameworks. Finding out the findings with DNA-based FEDs and developing associated correct theoretical models requires further experiments. Here, novel transducer techniques and technologies may hold great promise for ensuring repeatable and trustworthy biosensor signals. The authors have recently presented a method that accounts for this: instead of using "conventional" field-effect-based DNA sensors, their method uses the redistribution of ion concentration within the intermolecular spaces, which is caused by DNA hybridization, as a detection mechanism. Preliminary studies and theoretical estimates with synthetic ssDNA and polyelectrolyte multilayers have the potential to provide a large sensor signal in the tens of millivolts range. Additionally, the novel biosensor idea can function in both high- and low-ionic-strength solutions. Scientists from several fields, including bio-and electrochemistry, biophysics, device engineering, and analytics, should collaborate to address the complex and multidisciplinary problem of field-effect-based DNA biosensors.