Ultrasensitive particles offer new way to find cancer

September 1, 2011

MIT chemical engineers have designed particles that can detect microRNA inside living cells (Image source: Stephen Clifford Chapin)

MIT researchers have engineered a way to detect abnormal microRNA levels in the blood of cancer patients, raising the possibility of developing a simple blood test to diagnose or monitor the disease.

The technology consists of an array of tiny particles, each designed to latch onto a specific type of microRNA. By exposing blood samples to these particles, the researchers can generate a microRNA profile that reveals whether cancer is present. Each type of cancer — lung, pancreas, and so forth — has its own microRNA signature.

MicroRNAs, which are usually only about 20 nucleotides long, have been implicated in many other diseases, including HIV, Alzheimer’s disease, diabetes and cardiovascular disease. The human genome contains about 1,000 microRNAs, believed to fine-tune gene expression by blocking the messenger-RNA molecules that carry DNA’s protein-building instructions.

In their research on rapid microRNA profiling, the scientists showed that they could use tiny hydrogel particles, about 200 micrometers in length, to rapidly detect microRNA dysregulation patterns in RNA taken from four individuals with four different types of cancer. In their more recent research on multiplexed microRNA quantification, the researchers successfully detected microRNA in the blood serum of a prostate cancer patient.

Hydrogels are made of networks of water-loving polymer chains, which are conducive to the attachment of nucleic acids. Each of the researchers’ particles is decorated with millions of identical strands of DNA that are complementary to a specific microRNA target sequence.

When the particles were mixed with a blood sample, any microRNA present bound to its complementary DNA. Each DNA strand also contained a short sequence that bound to a fluorescent probe, added later. Using a custom-built microfluidic scanner, the researchers rapidly measured each particle’s fluorescence, revealing how much microRNA was present. The scanner read a chemical signature imprinted on each particle that revealed the type of microRNA being detected. The entire process took less than three hours.

In their later research, the scientists bumped up their particles’ sensitivity by amplifying the fluorescence generated by each particle. They achieved this by attaching multiple DNA label sequences to each microRNA target captured on the gel microparticles. These label sequences could then be attached to fluorescent probes.

This approach is 100 times more sensitive than other particle technologies for detecting microRNA, the researchers said. The technology can detect as few as 10,000 copies of a particular microRNA, and each serum assay requires only 25 microliters of sample.

Ref.: Stephen C. Chapin, et al., Rapid microRNA Profiling on Encoded Gel Microparticles, Angewandte Chemie, 2011; [DOI: 10.1002/anie.201006523]

Ref.: Stephen C. Chapin and Patrick S. Doyle, Ultrasensitive Multiplexed MicroRNA Quantification on Encoded Gel Microparticles Using Rolling Circle Amplification, Analytical Chemistry, 2011; [DOI: 10.1021/ac201618k]