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The Persistence of Engineering: Technology that Impacts People

Like most people dedicated to their field, engineering researchers long to know that their efforts make a difference in the world. Still, that vision can take years to achieve, especially considering the track that research often takes … from laying foundational knowledge to developing technological innovations in a laboratory setting and, hopefully, introducing the innovation, product, or service to the marketplace where it can more easily be accessed by consumers. Hsueh-Chia Chang, the Bayer Chair Professor of Chemical and Biomolecular Engineering (CBE) and director of the Center for Microfluidics and Medical Diagnostics, and his team feel blessed because they have not only been able to develop biotechnologies that may significantly improve global health and reduce health-care costs but they are also seeing some of those technologies begin to enter the market and make a difference in people’s lives, particularly in the area of early diagnostics.

Ask any physician: the earlier diseases can be detected and diagnosed, the better for the patient. Early detection typically lowers mortality rates because a disease can be treated at a stage where it is easier to disrupt. Early detection can help save lives and affect quality of life, not because it provides a “cure,” but because it gives physicians and patients options not available in the later stages of a disease. For example, the 5-year survival rate of pancreatic cancer is only 2% despite years of improvement in therapy. This is because current diagnostics can only detect the disease at a late stage.

Likewise, the sooner pathogens or diseases are detected in the environment, the lower the infection rate and hospitalization costs are likely to be. Dengue Fever, for instance, is the fastest-spreading mosquito-born viral infection in the world. Typically found in tropical and sub-tropical climates, the World Health Organization estimates that approximately half of the world’s population is at risk. While there is no effective vaccine or medication, early detection and subsequent access to proper medical care lowers fatality rates to below 1%.

The “environment,” however, does not always mean tropical rain forests or subSaharan deserts. In the United States alone, infectious diseases like MRSA, viral pneumonia, and sepsis have death rates around 20%. These diseases are responsible for approximately 20,000 deaths annually, with 90% of the infections occurring within hospital walls. The best way to combat this is with frequent screening that is very inexpensive, especially at home or at Point-of-Care (POC) locations. This screening would help identify the pathogen quicker to provide more immediate care while also allowing for isolation and quarantines as needed, to limit exposure.

But frequent screening necessitates that the screening devices must be plentiful and easy to use — in other words, inexpensive and fully integrated in a turn-key instrument, as easy and economical to find and use as a drug store pregnancy test or glucose test kit. To date, the POC nucleic acids diagnostics required for early identification/diagnosis of Dengue Fever, MRSA, etc., rely on a $50,000 instrument, and the tests, which must be administered by trained technicians, still cost more than $50 because of the expensive reagents needed. Frequent screening becomes economically viable only if these costs are reduced to $100 and $1, respectively. That is a tall order. But that — and more — is exactly what Chang and his group are working to achieve through fundamental cutting-edge research and integration of multiple innovative, but low-cost, nanotechnologies.

Instead of extensive pretreatment by a lab-bound technician, Chang’s technologies integrates nanoporous ion-selective membranes into their biochips for the nucleic acids diagnostics. These membranes are similar to the resins in a home water softener … and just as inexpensive. Under an electric field, which is supplied by a small hand-held ammeter that can be controlled by a laptop,  these on-chip membranes can desalt the sample, separate/concentrate the analyte, and even quantify specific nucleic acids with excellent selectivity. Unlike electrochemical sensing based on electron transfer across DNA wires, these technologies rely on non-equilibrium ion currents through the membranes, making them much more robust and specific. Chang’s technologies are designed to detect multiple targets at varying concentrations — millions of DNA copies for  infectious pathogens and fewer than 100 host microRNA. For the latter effort, he uses an ion-selective conic nanopore, which allows him to separate double-stranded DNA from single-stranded ones via a dynamic racheting mechanism like a very specific molecular diode.  For high-throughput screening of a large library of targets, Chang and team have developed several nanophotonic technologies that can screen and quantify a much larger number of targets than DNA microarray and require much less expensive optical instrument. They use a singular scattering from nanocones and plasmonic hot-spots from a field-controlled nanoparticle aggregation to enhance the sensitivity of the on-chip optical sensors, eliminating the need for expensive optics. For more abundant targets, his nanophotonic sensors require only an LED array and a miniature iPhone camera.

The group of integrated molecular sensing and sorting technologies developed in Chang’s lab form the basis for the handheld diagnostic device that is being produced commercially by FCubed, LLC. Located near Notre Dame, FCubed currently employs 16 full-time workers from the South Bend area. Completely portable, the device being produced can be used for real-time, on-site water quality and food testing. Clinical trials are now under way for MRSA screening at four U.S. hospitals. Chang and his team are working on additional technologies for oral and pancreatic cancer screening, as well as for monitoring of the dengue virus in mosquito samples. Two startups and a major international organization are negotiating with Notre Dame to license these technologies. Chang is also engaging Catholic philanthropic organizations, both at Notre Dame and in Europe, to find more applications for his low-cost diagnostic technologies. He is making a difference.