Engineers Created a New Electrical Chip That Detects DNA Mutations

June 16, 2016 | Kelly Tatera

The biosensor chip-electronically detects DNA SNPs
Photo credit: Jacobs School of Engineering, UC San Diego

In the future, it could be implanted in the body and wirelessly transmit information to laptops and smartphones.

By combining DNA nanotechnology with electronics, bioengineers at the University of California, San Diego have developed an electrical graphene chip that can detect mutations in DNA.

The researchers say that the technology could be used for a number of medical applications in the future, like blood-based tests for early cancer screening, real-time detection of viral and microbial sequences, and tracking disease biomarkers.

"We are at the forefront of developing a fast and inexpensive digital method to detect gene mutations at high resolution," Ratnesh Lal, professor of bioengineering, mechanical engineering and materials science in the Jacobs School of Engineering at UC San Diego, said in a press release.

The chip, which is at a proof-of-concept stage, is engineered to capture DNA molecules with a single error in its code and produce an electrical signal when these pieces of DNA bind to the chip’s DNA probe. The probe is a synthetic piece of double stranded DNA with a sequence coding for a specific type of single nucleotide polymorphism (SNP) — one of the most common genetic mutations.

Current SNP detection methods are relatively slow, expensive, and require bulky equipment.

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"We're developing a fast, easy, inexpensive and portable way to detect SNPs using a small chip that can work with your cell phone," said co-author Preston Landon, a research scientist in Lal's research group.

Essentially, the chip works by performing DNA strand displacement. This process occurs when a DNA double helix exchanges one strand for another complementary strand.

In this study, the chip’s DNA probe is a double helix with two complementary DNA strands — a “normal” strand and a “weak” one — that are engineered to bind weakly to each other. The normal strand is attached to the device’s transistor, and the weak one contains compounds, called inosines, that weaken its bond to the normal strand.

Based on this process, the researchers are able to see which strands contain the SNP mutation because they’ll bind to the normal strand and knock off the weak one.

“This is the first example of combining dynamic DNA nanotechnology with high resolution electronic sensing,” said Michael Hwang, co-first author of the study and materials science PhD student at UC San Diego. “The result is a technology that could potentially be used with your wireless electronic devices to detect SNPs.”

Additionally, the new technology improves upon former SNP detection methods, which typically use single-stranded DNA probes as opposed to double-stranded. With double-stranded DNA probes, only DNA strands that match perfectly to the normal strand are capable of knocking out the weak strand.

"A single stranded DNA probe doesn't provide this selectivity--even a DNA strand containing one mismatching nucleotide base can bind to the probe and generate false-positive results," Lal said.

The researchers say this is the first step towards a biosensor chip that could be implanted in the body to detect specific DNA mutations, and then wirelessly transmit real-time information to devices like smartphones or laptops.

But since the technology is at a proof-of-concept stage, there’s still a lot of work to be done. The researchers say that the next steps include scaling up the technology and adding wireless capability to the chip. They envision the chip being used to conduct liquid biopsies in clinical settings in the future.

In the research, which has been published in the Proceedings of the National Academy of Sciences, the authors conclude, “This technology opens opportunities for the development of more reliable and efficient diagnostic tools, including design and development of miniaturized, point-of-care, and implantable biosensors, for early detection of potentially life-threatening human diseases.”

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