Extreme point-of-care systems

The recent pandemic/epidemic episodes associated with viral diseases (influenza epi-centered in México in 2009, Ebola in West Africa in 2013-2015, and Zika in Latin America and Southeast Asia in 2016) are tangible and cruel reminders of the need for portable, low-cost, and easy-to-use diagnostic systems that can effectively address epidemic episodes in remote or underprivileged areas.

The diagnostic technologies currently available for identifying epidemic diseases are still very limited in scope. Yes, highly accurate, reproducible, and fast (some of them) diagnostics exist, but most of these are designed to be run in a conventional lab. They heavily depend on the use of costly and bulky equipment operated by highly-trained lab technicians. We urgently need portable, inexpensive, user-friendly, robust, and accurate diagnostic systems that can be reliably used outside the lab in remote or unprivileged areas, in disaster areas (i.e., after an earthquake or a hurricane), on battle frontlines, or in the home. Broadly defined, these are point-of-care (POC) diagnostics.

Today, the development of cost-efficient POC systems is a research niche of high relevance. Our work in the engineering front for POC systems is aimed at the development of extremely portable, simple, and cost-effective strategies for the diagnosis of epidemic diseases. Our ultimate aim is to develop “ideal” POC systems that can be easily and cost-effectively used wherever they are most needed.

Our use of various technologies and concepts makes our research approach to POC systems distinctive. We mainly use the recombinase polymerase amplification (RPA) reaction, as opposed to the more classical polymerase chain reaction (PCR). This is because PCR requires a repeated cycling of temperatures between 60 and 90 °C, whereas RPA is an isothermal nucleic acid amplification strategy that can be conducted optimally at 35–37 °C (but renders amplification in a wider temperature window of 25–42 °C). Therefore, RPA reactions can be run as a “single-well, one-temperature” process and do not require a thermocycler, thereby greatly simplifying the architecture of our POC systems.

Besides using RPA, we also design and build simple and inexpensive Arduino-based systems that allow us to follow the amplification of nucleic acids and discern between positive and negative samples by sensing electrical, optical, or physical changes. In addition, we use simple means to release and extract nucleic acids from complex biological samples (i.e., electrical discharges or temperature changes). The integration of simple, portable, and inexpensive methods for extraction, amplification, and on-line monitoring of the amplification in a single unit makes these systems extremely useful in POC settings. We are currently combining the use of RPA, microfluidic tools, nanotechnology, and simple electronics (mainly Arduino-based systems) to engineer extreme-POC platforms for diagnostic confirmation of Ebola, Zika, Dengue, influenza, Chikungunya, and HIV infections from extremely small saliva or blood samples.

Nanobiotechnology for Vaccine Development

Despite many centuries of learning experience, our technologies to produce vaccines are still based on the same old-fashioned (and not necessarily always highly effective) methodologies. These methodologies can be greatly improved by the combined use of modern biotechnology and nanotechnology concepts and tools.

We run a strong research program for novel technology that is focused (primarily) on influenza vaccines. Current influenza vaccine technology relies heavily on the expansion of influenza viruses in embryonated chicken eggs. Indeed, for this reason, the development and massive production of seasonal influenza vaccines is a cumbersome, expensive, and lengthy process that is not suitable for addressing epidemic or pandemic emergencies such as the one that we lived through in 2009 with the Influenza A/H1N1/2009 pandemic (i.e., the pandemic needs immediate vaccine for a new organism). We combine the use of biotech, microtech, and nanotech tools to develop better influenza vaccines.

For instance, we use recombinant technology to produce specific viral antigens (i.e., hemagglutinins or HA form influenza) in bacteria. Using these antigens, we functionalize nanoparticles to engineer cost-effective and safe vaccine candidates for veterinary and human use. In addition, we use microfluidics (i.e., in lab-on-chip systems) to test our nano-vaccines and we fabricate small continuous bioreactors to produce pilot scale amounts. Our unique and integral approach to vaccine development (science and technology from biodesign to continuous manufacture) enables the rapid design and engineering of novel vaccines for both existing and newly emerging public health threats.