The award will fund the development of human Organ Chips with automated in-line sensors to study vaccine responses
By Lindsay Brownell
(BOSTON) — The Wyss Institute for Biologically Inspired Engineering has been selected as one of three participants in a new federal ImmuneChip+ Program to develop advanced tissue chip platforms with immune system components and automated monitoring.
The program is co-sponsored by the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, and the National Center for Advancing Translational Sciences (NCATS).
As part of ImmuneChip+, the Wyss Institute received a contract award from BARDA that funds a one-year research program under the direction of Wyss Founding Director Don Ingber, M.D., Ph.D., focused on developing human lymphoid follicle chip (LF Chip) microfluidic culture devices that replicate immune vaccination responses, with instrumentation for in-line, continuous monitoring.
“The ongoing COVID-19 pandemic has made clear the need for rapid vaccine development, and this can be hampered by the lack of animal models that faithfully replicate human vaccination responses. While non-human primates have been used in the past, they are in short supply and they too frequently fail to predict human responses. The Wyss Institute is proud to be part of a program to advance development of human Organ Chip models of immune responses that can potentially replace animal models for preclinical evaluation of vaccines and drugs in the future,” said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Vaccination-on-a-chip
Lymphoid follicles (LF) are the smallest functional unit of lymph nodes, and contain aggregations of immune cells including B cells, T cells, and dendritic cells. LFs coordinate the body’s immune response against pathogens and are a key part of the vaccination process, in which a “memory” of a mock invader is created so that an effective immune response can be mounted the next time the pathogen is encountered.
The Wyss Institute team, led by Girija Goyal, Ph.D. working with Ingber, has been able to replicate the vaccination process in vitro in an Organ Chip. Their goal now is to engineer Organ Chip culture systems that can continuously monitor the tissue’s responses to increase understanding of health and disease without putting human test subjects at risk, and enable more efficient assessment of potential treatments.
To achieve this goal with LF Chips, the Wyss team will build a microfluidic sensor cartridge that senses and samples multiple biomarkers in the LF Chip repeatedly over time. They will then integrate it into existing Organ Chip culture systems, develop an automated microfluidic readout instrument using commercial parts, and demonstrate in-line sensing of two or more human vaccine-related biomarkers.
This will be accomplished by leveraging recent work focused on instrumented microfluidic Organ Chip devices made by Adama Sesay, Ph.D., and major advances in electrochemical sensing of biomarkers in small volumes made by Pawan Jolly, Ph.D. as part of the Institute’s Bioinspired Therapeutics and Diagnostics Platform led by Ingber.
“This project an excellent example of how the different technologies we have developed at the Wyss Institute can work in concert with each other to advance research and knowledge. While our sensor technology was initially created for diagnostic applications, it can also be used for monitoring vaccine response by integrating it with our Organ Chip technology,” said Jolly.
In addition to the Wyss Institute’s work, other BARDA awardees will be developing their own instrumentation to collectively create a set of mature ImmuneChips that enable the study of how the body’s reaction to immune threats plays out across multiple organs. The Wyss Institute team successfully demonstrated this human Body-on-Chips system in the past by linking eight different types of Organ Chips together via a common vascular network.
“This is an intense but exciting project whose ambition is to enhance the usability of organ chips for personalized medicine and drug development, and will also help position them for wider use in academic, governmental, pharmaceutical, and medical research,” said Sesay, who is a Senior Staff Engineer at the Wyss Institute.