Detecting cancer in a drop of blood

01 Aug 2014. Scientists in NUS have developed ultrasensitive assays for the detection of circulating microRNAs in blood.

A microRNA (miRNA) is a small non-coding RNA molecule found in plants and animals. It functions in transcriptional and post-transcriptional regulation of gene expression. When the first miRNA was discovered in 1993, scientists believed that it would not occur frequently. Today, it has become clearer that miRNAs is a group of important biomarkers for many diseases including cancer. This is especially true for miRNAs found in blood. There is evidence to indicate that circulating miRNA profiles in blood are closely associated with many types of cancer. Besides using it in early detection, circulating miRNAs can therefore also be used in the prediction of response to anticancer agents.

Conventionally, miRNAs are detected by quantitative polymerase chain reaction (qPCR). Quantitative PCR amplifies a single piece of miRNA to millions of copies in order to detect it easily. Though it is very effective, the use of qPCR has many disadvantages. The three disadvantages are the high level of skills required, time needed to prepare a suitable sample and cost. Ideally, miRNA assays should be sensitive enough to provide quantitative information for reproducible detection of certain miRNAs, and easy to perform without the need for expensive reagents or equipment. To meet this goal, a team of scientists led by Professor GAO Zhiqiang from the Department of Chemistry in NUS has developed assays for the detection of circulating miRNAs (see Figure). Compared to other miRNA assays, their assays exhibit several distinct advantages: (1) excellent sensitivity and selectivity, (2) the simplicity of label-free detection, and (3) freedom from miRNA labeling. The assays improve the detection of circulating miRNAs in blood with minimal or no sample pretreatments. This offers an excellent opportunity for the development of a simple, robust, and ultrasensitive miRNA detection platform for use at point-of-care.

Image shows the capturing DNA strands (black) form duplexes with target miRNA strands (blue) during hybridization. Concurrently, all hybridized DNA-miRNA duplexes are cleaved off the biosensor by an enzyme, exposing part of the electrode and releasing target miRNA strands back to the sample solution for further hybridization. The size of the exposed area is proportional to the number of the target miRNA strands. (Picture credit: American Chemical Society)

References

1. Y Ren, H Deng, W Shen, Z Gao. “A Highly Sensitive and Selective Electrochemical Biosensor for Direct Detection of MicroRNAs in Serum.“ Analytical Chemistry 85 (2013) 4784.

2. Y Ren, H Deng, W Shen, Z Gao. “A Real-time Colorimetric Assay for Label-free Detection of MicroRNAs Down to Sub-femtomolar Levels.” Chemical Communications 49 (2013) 4959.

3. Y Ren, H Deng, W Shen, Z Gao. “A Label-Free Biosensor for Electrochemical Detection of Femtomolar MicroRNAs.” Analytical Chemistry 85 (2013) 1624.

4. Y Ren, H Deng, W Shen, Z Gao. “A highly sensitive microRNA biosensor based on hybridized microRNA-guided deposition of polyaniline.” Biosensors & Bioelectronics 60 (2014) 195.