Multi-Particle System for Capture and Detection of Cellular and Molecular Analytes (Case No. 2025-267)

Summary:

UCLA researchers in the Department of Bioengineering have developed a novel multi-particle system that selectively confines cells and molecular reactions within cavities formed by interacting particles.
      
Background:

Screening and selecting cells with specific, beneficial traits has become a vital process in using cell-derived products for advances in biotechnology and life science research. Prevalent examples include screening for primary B cells that rapidly produce functional antibodies, activated T cells based on cytokine secretion profiles, and screening for therapeutically potent mesenchymal stromal cells based on extracellular vesicle secretion. Since genetically identical cells can behave differently, it’s crucial to examine large populations of individual cells to enrich cells with desirable properties. Thus, studying individual cells to identify molecular differences helps explain why cells respond and function in unique ways to treatment. This approach is fundamental to both therapeutic development and basic life science research. To do so, researchers compartmentalize individual cells into small spaces, which help map molecular outputs to individual cells. Current methods are slow, expensive, complex, prone to signal mixing, and have low compatibility with certain cell types. Thus, there is a need to improve affordability and accessibility of single-cell analysis, all while offering improved control and compatibility. 

Innovation:

Researchers at UCLA have developed a novel system that confines cells and molecular reactions into cavity-containing particles, which are sealed through interactions with capping particles. These interactions can be induced by simple mixing and centrifugation, creating millions of capped particles without the need for complex microfluidic devices. These compartments can be sealed to restrict particles based on size, enabling precise control over the reaction environment. Particles can be functionalized using barcodes and reactive moieties, enabling high-throughput identification and enhanced molecular interactions. Additionally, this system is compatible with a wide variety of cells and a diverse range of assays. Examples include motile and fast-growing cells, hybridoma screening, growth assays, secretion assays, gene expression assays, and colony forming assays. This novel multi-particle system offers an improved alternative over current single-cell screening technologies by overcoming limitations of affordability, scalability, functionality, and accessibility. Potential applications include ex-vivo cell processing, single-cell analysis, high-throughput drug screening, antibody discovery, biomarker screening, high sensitivity or digital molecular assays, and precision medicine.

Potential Applications:

●    Single-cell analysis
●    High-throughput screening for drugs
●    Cell identification and sorting
●    Disease detection
●    Biomarker screening
●    Characterization/Optimization of cells
●    Microbial analysis
●    Single-cell sequencing

Advantages:

●    Cost
●    Accessibility
●    Scalability
●    High-throughput 
●    Compatibility
○    Cells
■    ranging from motile to fast-growing, suspension to adherent.
○    Assays
■    secretion, gene expression, killing, growth, etc
●    Control
○    reaction environment

Development-To-Date: First successful demonstration of the invention completed.

Related Papers:

• Ghosh, R., Arnheim, A., van Zee, M., Shang, L., Soemardy, C., Tang, R. C., ... & Di Carlo, D. (2024). Lab on a particle technologies. Analytical Chemistry, 96(20), 7817-7839.
• Mellody, M., Nakagawa, Y., James, R., & Di Carlo, D. (2025). Multi-reactive hydrogel nanovials for temporal control of secretion capture from antibody-secreting cells. Lab on a Chip, 25(6), 1565–1574. https://doi.org/10.1039/d4lc01056f 
• Michael Mellody, Yuta Nakagawa, Alyssa Arnheim, Lily Shang, Catherine Soo, Natalie Tsubamoto, Sarah Taylor, Sumedha Shastry, Wesley Luk, Ian Morales, Richard James, Dino Di Carlo, Sealable capped nanovials for high-throughput screening of cell growth and function, bioRxiv 2025.06.29.662236; doi: https://doi.org/10.1101/2025.06.29.662236 

Reference:

UCLA Case No. 2025-267

Lead Inventor:  

Dino Di Carlo