University of Connecticut biomedical engineering professor Changchun Liu is leading a new research effort that could help transform how clinicians detect and monitor cancer using a simple blood test.

Liu has received a four-year National Institutes of Health (NIH) R01 research grant totaling more than $2.5 million for a project titled “Asymmetric CRISPR Approach for Nucleic Acid Quantification.” The award will support the development of a next-generation CRISPR-based diagnostic platform designed to accurately measure disease biomarkers in blood samples, with a particular focus on early cancer detection.

The NIH R01 is among the most competitive and prestigious funding mechanisms, supporting innovative research projects with strong potential for scientific and societal impact.

“Our goal is to develop a simple, sensitive, and quantitative platform for measuring nucleic acid biomarkers from blood samples,” says Liu. “By combining CRISPR technology with microfluidic systems, we hope to make advanced molecular testing more accessible for clinical and point-of-care applications.”

Liu is a professor in the Department of Biomedical Engineering, which is a joint effort from UConn Health and the UConn College of Engineering.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology is widely recognized for its gene-editing capabilities, but researchers have increasingly adapted it for diagnostic applications. While many existing CRISPR-based tests can determine whether a target molecule is present, Liu’s team is focused on answering a more complex question: how much of that target is present.

The project centers on developing an “asymmetric CRISPR” approach, which engineers the CRISPR reaction to provide quantitative measurements rather than simple positive-or-negative results.

This capability is particularly important for detecting biomarkers that exist at extremely low concentrations in the bloodstream, such as exosomal microRNAs associated with early-stage cancers.

“Many disease biomarkers are present at very low levels, especially during the earliest stages of cancer,” Liu explains. “Reliable quantification can improve disease detection, monitoring, and treatment decisions.”

Current laboratory methods, including quantitative polymerase chain reaction (qPCR), provide accurate measurements but often require expensive instrumentation, specialized laboratories, and trained personnel. Liu’s team aims to simplify the process by integrating the CRISPR technology into a portable microfluidic chip capable of analyzing blood samples with greater speed and accessibility.

The new project builds on years of research conducted in Liu’s laboratory focused on CRISPR diagnostics and point-of-care technologies.

In 2023, Liu and collaborators reported advances in CRISPR diagnostic performance in a study published in Nature Communications. The research demonstrated new strategies for improving the sensitivity and efficiency of CRISPR-based molecular testing.

The NIH-funded project expands on that foundation by moving the technology closer to real-world clinical use.

“Unlike traditional CRISPR diagnostics that primarily provide yes-or-no answers, our approach enables quantitative nucleic acid measurement through a simplified workflow,” says Liu. “The integration of microfluidics also improves automation and portability, creating opportunities for broader clinical implementation.”

Over the next four years, the research team will work to refine the technology and evaluate its potential for analyzing clinical blood samples, with cancer detection serving as a primary application.

For Liu, the greatest promise of the research lies in its potential to improve patient outcomes.

“The most exciting aspect is enabling simple blood-based tests for early cancer detection and disease monitoring,” Liu says. “These technologies could help clinicians detect disease earlier and guide more precise treatment decisions.”

Beyond cancer, the platform could eventually support a wide range of diagnostic applications, helping expand the reach of CRISPR-based technologies into routine clinical practice.

As the project moves forward, Liu and his team hope their work will contribute to a future where advanced molecular testing is faster, more affordable, and accessible to patients wherever care is delivered.