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Journal Club: New chip allows for rapid, low-cost disease diagnosis from small DNA, RNA samples

A new point-of-care biochip enables rapid detection of nucleic acids in blood samples, paving the way for quick, cheap tests for HIV, MRSA, and numerous other diseases.
Video Credit: Yeh et al. Sci. Adv. 2016;3:e1501645

Ideally, an urgent diagnosis occurs rapidly and at a patient’s side. Blood tests sent to a lab waste precious time. Rapid, onsite tests, sometimes called “point-of-care,” can be especially valuable in remote, resource-poor settings.

Now scientists have developed a prototype, low-cost, handheld, disposable chip that can detect viral and bacterial DNA or RNA directly from blood samples within about 30 minutes, findings detailed online March 22 in Science Advances.

Current conventional methods to analyze DNA or RNA often require a time-consuming multi-step process and expensive lab equipment. Study senior author Luke Lee at the University of California at Berkeley and his colleagues sought to develop a simpler, cheaper solution using microfluidic chips that shuffle liquids within microscopic channels. They aimed to create a “lab-on-a-chip” that could analyze genetic material in much less time, with fewer materials, and at a lower cost than a conventional laboratory.

The result is a chip they call SIMPLE (self-powered integrated microfluidic point-of-care low-cost enabling). The transparent silicone rubber device is about the size of a microscope slide. It accurately detected RNA from the HIV-1 virus and DNA from the Methicillin-resistant Staphylococcus aureus (MRSA) bacterium in roughly a half-hour. This work “presents a practical approach for integrating a number of microfluidic innovations into one package,” says biomedical engineer Samuel Sia at Columbia University in New York, who did not take part in this research.

The 2.5-by-7.5-centimeter SIMPLE chip relies on three technical advances. First, a user mixes blood samples with chemical reagents and then loads the mixture into wells in the chip. The chip is then incubated on reusable heat packs or in simple ovens, which help drive chemical reactions that detect tiny amounts of genetic material from the bacteria or virus of interest—for instance, anywhere from roughly 10 to 100,000 copies of MRSA DNA per microliter.

Next, the scientists developed a method to easily prepare samples for analysis on the chip by filtering plasma from human blood in a single step. The plasma gets separated into more than 200 microscopic wells for analysis.

Finally, the chip essentially carries its own power source in the form of two “vacuum batteries,” which are voids in the chip. When the chip releases this vacuum, it pulls air through lung-like structures in the chip, which helps drive microscopic droplets of fluid around the device. A method called recombinase polymerase amplification boosts nucleic acid amounts to detectable levels using enzymes; crucially, no added heat is necessary for the reaction.

“Our SIMPLE biochip can be used for molecular-level medical diagnostics of many different diseases,” Lee explains, citing for example malaria, Ebola, or dengue. The chip’s layout also could make it possible to perform tests for multiple diseases on the same chip.

The chip’s materials and reagents cost less than $10 per device, the researchers report, and mass production could drive down the price further. The scientists envision using the device in rural third-world country villages that lack centralized laboratories, electricity, medical personnel, and the funds for costly equipment.

Right now, the chip’s results are analyzed using a benchtop microscope. “In the future, I would be interested to see if they can detect the signal without the need for an external microscope,” says Sia. The researchers say they plan to integrate a simple, low-cost, handheld imaging device with the chip, and to conduct field trials.

Eventually they’d also like to pre-load all of the reagents into the chip so that users only have to add the blood samples. Lee aspires to create an advanced version of his team’s lab-on-a-chip that can genetically analyze blood samples in just five minutes, he says.

Categories: Applied Biological Sciences | Biochemistry | Infectious disease | Journal Club | Medical Sciences and tagged | | | |
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