TRAILBLAZER: Bringing the Solid State to Life with Cell Crystals to Transform Biosensing in Environmental, Health Care, and National Security Applications

About This Grant

The ability to detect pathogens, toxins, and biological/chemical threat agents is critical to supporting public health, and national security. However, such detection is limited by instrument sensitivity and portability, slow analysis methods, and the inability to detect unknown hazardous substances. For example, to protect public health after extreme weather events, toxins and harmful bacteria in waterways must be monitored over vast distances, yet water quality samples are typically collected in the field and brought to a laboratory for analysis using time-consuming methods and non-portable instrumentation. One potential way to overcome these limitations is to use living cells as biosensors in versatile, portable, and sensitive devices. Decades of research have provided the ability to manipulate the genetic circuitry of living cells, programming them like computers. Unfortunately, biosensing devices made from such cells are not currently as reliable as everyday digital electronics. Taking inspiration from digital technology now relied upon worldwide, this project will develop biosensors that harness the fundamental physical principles underlying the functionality of modern electronic devices. The project will broaden participation in STEM fields by developing a program to guide team research, mentoring, and training activities that tap into the full spectrum of available talent. The research team will hold biannual workshops to learn new ways to expand the range of thoughts, ideas, impacts, and approaches for defining and solving important questions in research. Partnering with a local museum, an exhibit for continuous use in public education and outreach will be created, assembling high-school and undergraduate research teams to build the exhibit. This TRAILBLAZER project aims to develop biotechnology inspired by solid-state physics while leveraging the powerful complexity of genetics. Coherent, spatiotemporally patterned, and highly controlled collective biological states will emerge upon integrating programmed cell communication with cell positioning on lattices. This structure-function hypothesis is drawn from solid-state materials; semiconductors, magnets, and superconductors are made by arranging specific atoms into specific crystal structures, but the atoms alone do not have the properties of their assemblies. Thus, as in atomic crystals, emergent collective states can be designed by matching cell programming to cell assembly. Creating new biological states by integrating a top-down structural strategy with bottom-up cell-engineering has never been attempted; crystallinity has not yet been leveraged to control collective cell behavior. Thus, the main research thrusts are: (1) develop new types of engineered cells and synthetic biology programming specifically for incorporation into crystal lattices; (2) bring together theoretical modeling, advanced bio-fabrication, and experimentation to create and study the novel biological phases that emerge in analogy to the collective phases that emerge in solid state materials. The project will introduce new ways to think of biotechnology development, which will be used to create totally new classes of biosensors and other cell-based devices. Anticipated Transformative Impact: Disruptive options for 3-D biomanufacturing beyond bioprinting. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.