Toward biosensors for the detection of circulating microRNA as a cancer biomarker: an overview of the challenges and successes

Abstract

Considerable attention has been dedicated to developing feasible point-of-care tests for cancer diagnosis and prognosis. An ideal biomarker for clinical use should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. The role of microRNAs (miRNAs) in the regulation of different cellular processes, the unique altered patterns in cancer patients and presence in body fluids in the stable form, points to their clinical utility as blood-based biomarkers for diagnosis, prognosis, and treatment of cancer. Although a variety of selective and sensitive laboratory-based methods are already exist for the detection of circulating miRNA, having a simple, low-cost and rapid assay, which could be routinely used in clinical practice, is still required. Among different approaches that have developed for circulating miRNA detection, biosensors, due to the high sensitivity, ease of use, short assay time, non-toxic experimental steps, and adaptability to point-of-care testing, exhibit very attractive properties for developing portable devices. With this view, we present an overview of some of the challenges that still need to be met to be able to use circulating miRNAs in clinical practice, including their clinical significance, sample preparation, and detection. In particular, we highlight the recent advances in the rapidly developing area of biosensors for circulating miRNA detection, along with future prospects and challenges.

Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA-155 in breast cancer

“…Aberrant expression levels of miRNAs have been observed in many solid tumours, including breast cancer (Fu et al, 2011), accounting their dysregulated expression in cancer. In addition, miRNAs are stable in the blood and have high/low expressions that can be correlated to chemo-resistance, (Kong et al, 2010; Tavallaie et al, 2015). …”

Nanomedicine concepts in the general medical curriculum: initiating a discussion

“…20 Using a number of in vitro and in vivo methods, 89 nanodiagnostic devices are able to detect the presence of relevant biomarkers (eg, surface proteins of cancerous cells or circulating tumor DNA) at much lower levels, and potentially are able to measure the presence of target biomarkers at the level of single cells and molecules. 68,90 In addition to point-of-care nanodiagnostic methods that have been developed for a range of cancers, 91,92 point-of-care nanodiagnostics continue to be developed for several other pathologies, including Alzheimer's disease, 20,93 diabetes, 94,95 and a number of viral and bacterial infections.…”

A novel electrochemical nanobiosensor for the ultrasensitive and specific detection of femtomolar-level gastric cancer biomarker miRNA-106a

“…Moreover, it has been demonstrated that the circulatory miRNAs are noticeably resistant to RNase digestion, non-physiologic pH values, and high temperature. Hence, these miRNAs have been considered as promising biomarker for early cancer detection [8–9]. …”

“…On the other hand, the technical challenges for the quantitative analysis of miRNA become more complex due to their small size, low abundance, and high sequence similarity. In an effort to resolve the mentioned limitations, biosensor technology was suggested as an alternative method for sensitive, specific and non-invasive miRNA detections in early cancer diagnosis [8]. Biosensors are commonly defined as devices composed of recognition elements interfaced with a transducer, which finally transform a capture process into a detectable output signal.…”

“…Over the past years, miRNAs have been one of the most attractive targets for the construction of electrochemical nanobiosensors [8,21,28]. There are numerous studies on fabricating electrochemical nanobiosensors for the detection of label-free or labeled miRNA.…”