In this case, the components consist of a sheet of paper or glass fiber sandwiched between a plastic or metal block and a glass cover. The blocks, which are about half an inch on each edge, can snap together along any edge. Some of the blocks contain channels for samples to flow straight through, some have turns, and some can receive a sample from a pipette or mix multiple reagents together.
The blocks can also perform different biochemical functions. Many contain antibodies that can detect a specific molecule in a blood or urine sample. Those antibodies are attached to nanoparticles that change color when the target molecule is present, indicating a positive result.
These blocks can be aligned in different ways, allowing the user to create diagnostics based on one reaction or a series of reactions. In one example, the researchers combined blocks that detect three different molecules to create a test for isonicotinic acid, which can reveal whether tuberculosis patients are taking their medication.
The blocks are color-coded by function, making it easier to assemble predesigned devices using instructions that the researchers plan to put online. They also hope that users will develop and contribute their own specifications to the online guide.
The researchers also showed that in some ways, these blocks can outperform previous versions of paper diagnostic devices. For example, they found that they could run a sample back and forth over a test strip multiple times, enhancing the signal. This could make it easier to get reliable results from urine and saliva samples, which are usually more dilute than blood samples, but are easier to obtain from patients.
“These are things that cannot be done with standard lateral flow tests, because those are not modular — you only get to run those once,” says Hamad-Schifferli.
The team is now working on tests for human papilloma virus, malaria, and Lyme disease, among others. They are also working on blocks that can synthesize useful compounds, including drugs, as well as blocks that incorporate electrical components such as LEDs.
The ultimate goal is to get the technology into the hands of small labs in both industrialized and developing countries, so they can create their own diagnostics. The MIT team has already sent them to labs in Chile and Nicaragua, where they have been used to develop devices to monitor patient adherence to TB treatment and to test for a genetic variant that makes malaria more difficult to treat.
Catherine Klapperich, associate dean for research and an associate professor of biomedical engineering at Boston University, says the MIT team’s work will help to make the diagnostic design process more inclusive.
“By reducing the barriers to designing new point-of-care paperfluidics, the work invites nonexperts in and will certainly result in new ideas and collaborations in settings all around the world,” says Klapperich, who was not involved in the research. “The practical demonstrations of the system presented here are poised to be immediately useful, while the possibilities for others to build on the tool are large.”
The researchers are now investigating large-scale manufacturing techniques, and they hope to launch a company to manufacture and distribute the kits around the world.
“We are excited to open the platform to other researchers so they can use the blocks and generate their own reactions,” Young says.
|The research was funded by a gift from Autodesk and the U.S. Public Health Service.|
Ampli: A Construction Set for Paperfluidic Systems, Elizabeth A. Phillips, Anna K. Young, Nikolas Albarran, Jonah Butler, Kaira Lujan, Kimberly Hamad-Schifferli, Jose Gomez-Marquez. Advanced Healthcare Materials 2018; 1800104 DOI: 10.1002/adhm.201800104