Summary:
UCLA researchers in the Department of Bioengineering have developed a novel enzyme-based particle platform that enables amplified molecular detection in fully aqueous systems for sensitive, multiplexed analysis of low-abundance analytes.
Background:
The detection of molecules and determination of enzymatic activity are foundational across clinical diagnostics, pharmaceutical development, molecular biology, and environmental monitoring. Traditionally, these analytical reactions have relied on macro-scale tools such as standard test tubes or multi-well plates. While effective, these conventional approaches consume large volumes of valuable samples and costly reagents, which limit cost-effectiveness and sensitivity when detecting low-abundance analytes. Micro-scale platforms, including microfluidic droplets and microwells, address some of these limitations by reducing reaction volumes and enabling digital quantification. However, this improvement often comes with added complexity, as many droplet-based systems still require specialized equipment, oil-based partitioning, and complex imaging or reader systems. Surface-based enzyme assays, such as ELISA and western blotting, offer a more practical alternative for target separation and signal localization, but their larger stationary surfaces limit miniaturization, multiplexing, and high-throughput digital quantification. There remains an unmet need for a practical analytical platform that combines the sensitivity of micro-scale digital assays with the accessibility of solid-phase enzyme-based detection.
Innovation:
UCLA researchers have developed a novel enzyme-based particle platform that amplifies molecular detection signals directly on solid particle surfaces in a fully aqueous system. The technology uses functionalized particles as localized reaction sites, allowing enzyme-generated signals to remain concentrated on individual particles rather than diffusing through the surrounding solution. The platform leverages substrates not previously utilized for localized deposition, including ADHP (amplex red dihydroxyphenoxazine), enhancing detection sensitivity and quantification via digital signals. In addition, the invention employs hydrogel matrices instead of conventional nitrocellulose membranes or tissue sections to diversify applicability to a broad array of sample types. By localizing signal generation, the platform supports sensitive detection of low-abundance analytes while enabling multiplexed reagent or sample analysis without relying on traditional water-in-oil droplet partitioning. This approach combines the sensitivity and quantitative potential of micro-scale digital assays with the practical workflow of solid-phase enzyme detection, making it broadly applicable to biomarker detection, molecular diagnostics, biosensing, drug discovery screening, and research assays.
Potential Applications:
- Molecular diagnostic assays
- Biomarker detection for clinical samples
- Biosensing platforms for proteins, nucleic acids, metabolites, and other analytes
- Drug discovery screening and enzyme activity assays
- Environmental monitoring for low-abundance targets and biohazardous materials
- Research tools for biochemical pathway analysis
Advantages:
- Enables sensitive detection of low-abundance analytes
- Supports digital and quantitative assay readouts
- Allows multiplexed detection of multiple analytes or samples
- Reduces reliance on water-in-oil droplet partitioning and specialized microfluidic workflows
- Improves signal localization for stronger signal-to-noise performance
- Leverages substrates that generate digital vs analog signals
- Reduced cross-reactivity
State of Development:
The technology has been developed and successfully demonstrated using enzyme-based signal accumulation on particles. Further validation across additional analytes, sample types, and assay formats would support broader implementation.
Related Publications and Patents:
- System and Methods for Amplified Detection of Molecules on Microparticles (Case No. 2021-002)
- Systems and methods for the amplified detection of molecules on microparticles
Reference:
UCLA Case No. 2026-130-1
Lead Inventors:
Dino Di Carlo, Bioengineering Department Chair