CAMBRIDGE, MA—Major infectious diseases, like COVID-19, often go undetected until they spread. Spotting the problem in a community isn’t easy, in part because infectious disease detection, which is the foundation for surveillance and contact tracing, can take hours, if not days. Compounding the problem is that traditional detection assays are designed a priori while newer bio detection technologies have been slow to move from the lab into general use.
Now scientists are developing a portable device that is easily configurable for screening thousands of pathogens in minutes, not hours. The device will incorporate recent advances in biotechnology, imaging analysis and microfluidics. The aim is to improve the speed of treatment and enhance the standard of care for the public and to equip the military with new biosurveillance technology.
Rachel Fezzie, a biochemist and molecular biologist at Draper, says infectious disease detection needs to be faster, lower in cost and field-ready. “The development of a rapid, low-cost diagnostic device that is capable of detecting 1,000 biomarkers in one processing cycle is an important step forward in improving infectious disease detection,” Fezzie explains. “A device with the ability to detect pathogens sooner and in a greater variety would improve public health, add protections for military units and provide critical information to medical decision-makers within minutes.”
Fezzie and her colleagues at Draper are developing just such a technology as part of a team recently selected by the Defense Advanced Research Projects Agency (DARPA). Led by MRIGlobal, the team is developing a massively multiplexed device (MMD) for DARPA’s “Detect It with Gene Editing Technologies” (DIGET) program. The aim, says DARPA, is to incorporate gene editors into detectors for distributed health biosurveillance and rapid, point-of-need diagnostics for endemic, emerging and engineered pathogenic threats.
The foundation for the MMD is DETECTR™, a CRISPR-based detection platform developed by Mammoth Biosciences, which is a member of the MRIGlobal team. The platform has been proven as a rapid detection diagnosis technology that uses a gene editing molecular tool to find a specific genetic sequence within a sample.
The MMD will incorporate several innovative technologies developed by Draper. Fluid routing throughout the disposable cartridge will be controlled by Draper’s proprietary electromagnetic pump and valve technology, ideal for applications with low size, weight and power requirements. Draper’s demonstrated experience in functionalizing glass substrates and printing compact, high-density DNA arrays will directly inform the development path to scale Mammoth’s DETECTRTM chemistry to 1,000-plex via a microarray of Cas/gRNA complexes. Each Cas/gRNA complex is designed to detect a unique pathogen.
The MMD will also use a new approach to optical detection through development of a miniaturized, simple, lens-free system that has no moving parts, making it attractive for field deployment. Reconfiguration of the microarray will be enabled by printing array chips with new Cas/gRNA complexes, a process expected to take 24 hours or less.
“The MMD”—according to John Julias, Draper’s program manager for DIGET—“seeks to fundamentally alter the concept of operations for biosurveillance and diagnostic detection by increasing throughput, sensitivity and usability to levels unmatched by existing technologies. A single run of the MMD promises to provide not only species- or strain-level identification but also information on genetically encoded characteristics such as antimicrobial resistance, as well as gene expression data to indicate disease severity in a person.”
The projected sample-to-answer time of 15 minutes with the MMD will enable more assays to be run in a day, allowing appropriate action to be taken in near real-time, Fezzie explains. “Currently, you would need next-generation sequencing to identify such a broad a range of pathogens, and that typically takes days to perform by highly skilled laboratory staff.”
Draper’s DIGET work is supported by the company’s Bioengineering, Microsystems and Advanced Material divisions, and it is managed by its Special Programs Office.