Lab on a Chip

By Christina Phillis

Diagnosing disease in remote areas with limited resources can be a difficult feat. Quantitative testing, which requires the ability to measure not just the presence or absence of biomolecules but the precise concentration, is difficult to perform outside of the clinical setting. Those sorts of tests typically require both large and expensive equipment as well as trained personnel and access to electricity. One essential requirement for healthcare providers in these challenging situations is the ability to produce robust readouts despite harsh environments and user errors. These readouts are essential for detecting molecular markers that aid in the diagnosis of disease.

Researchers in the lab of Rustem Ismagilov, Caltech’s Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering for Medicine, have invented a new visual readout method for diagnostics using analytical chemistries and image processing. The new method provides unambiguous quantification of single nucleic-acid molecules, and the best part is: it can be performed by any cell phone camera. A paper published in the journal ACS Nano describes and validates the visual readout method using RNA from the hepatitis C virus.

“The readout process we developed can be used with any cell-phone camera,” Jesus Rodriguez-Manzano, a postdoctoral scholar in chemical engineering and one of two first authors on the paper, told Science Daily. “It is rapid, automated and doesn’t require counting or visual interpretation, so the results can be read by anyone ― even users who are color blind or working under poor lighting conditions. This robustness makes our visual readout method appropriate for integration with devices used in any setting, including at the point of care in limited-resource settings. This is critical because the need for highly sensitive diagnostics is greatest in such regions.”

How It Works

With SlipChip, a microfluidic device, researchers are able to quantify concentrations of single molecules such as DNA or RNA. The portable lab-on-a-chip was invented in the Ismagilov lab several years ago. It consists of two credit card-sized, stacked glass plates with a thin layer of lubricating fluorocarbon between them. The top plate has wells and the bottom plate has wells and ducts on its surface. The sample is added to the interconnected channels of the SlipChip. As the plates are slipped over each other, fluidic paths are formed when the ducts in the lower plates and the wells in the upper plate line up. Complex reactions occur as each well is either joined or separated and reactants and molecules are either brought into contact or isolated. The design of the chip allows the user to control the sample and prevent contamination.

To take the SlipChip technology further in aiding healthcare workers in remote locations, indicator chemistries are integrated into the wells of the device. Based on whether the result is positive or negative, the wells change color after the amplification reaction is performed. If one of these devices was being used to count HCV RNA, for example, a well would turn blue if it contained an RNA molecule that amplified during reaction and a well would remain purple if it lacked an RNA molecule.

Next, any user hoping to understand the results of this readout would take a picture of the entire SlipChip using a camera phone. The photo is then processed, and the colors detected by the camera’s sensor are transformed into an unambiguous readout of positives and negatives. Earlier iterations of the SlipChip technology used a chemical that would fluoresce after a reaction within the well took place. Those readouts are too subtle for a cell-phone camera to detect and require certain lighting conditions, which are difficult to achieve in settings that lack electricity.

The researchers of this study were able to upload their image to a cloud-based server where custom software determined the concentration of a sample and sent the results back in an email. This is a promising new option for healthcare practitioners who find themselves in settings with limited resources.