High-throughput droplet microfluidics platform for discovering stable sweet proteins
A droplet-based microfluidics assay that screens millions of sweet protein mutants to identify acid- and heat-stable variants. The platform reduces discovery timelines from years to months and is adaptable across multiple sweet protein types, enabling faster development of natural sugar alternatives for food and beverage applications.
Overview
This solution offers a high-throughput droplet-based microfluidics platform designed to discover and engineer stable sweet proteins that can serve as natural sugar alternatives. Traditional rational protein engineering approaches face significant limitations because detailed structural information is often unavailable, and even when structures are known, linking specific mutations to functional improvements is challenging. The proposed assay overcomes these barriers by screening millions of sweet protein mutants within picolitre water-in-oil droplets, dramatically accelerating the discovery process.
The platform reduces protein discovery timelines from years to months and is highly adaptable to different types of sweet proteins. By identifying variants with enhanced acid and heat stability, the technology addresses key challenges in formulating natural sweeteners for food and beverage products, where processing conditions and shelf-life requirements demand robust protein performance.
Technical specifications
Core capabilities:
- Picolitre water-in-oil droplets and microcapsules engineered to encapsulate and culture microbes producing recombinant sweet proteins
- Construction of sweet protein expression pathway libraries with transformation into suitable host strains such as E. coli, yeast, or fungi
- Custom-designed sweet protein-human tongue T1R2/T1R3 receptor binding assay for functional screening
- Fluorescence-activated cell sorting (FACS) to isolate functional and acid/heat-stable sweet protein-containing droplets
- Adaptable platform architecture compatible with multiple sweet protein types
Key advantages:
- Screens millions of mutants in a single high-throughput workflow
- Reduces discovery timelines from years to months
- Built on validated droplet microfluidics expertise previously applied to enzyme engineering, antibody pair identification, and cytokine capture assay development
- Complementary to existing sugar-reduction technologies co-developed with major food industry partners
Technology readiness level
The platform is currently at an advanced development stage. The droplet and microcapsule systems suitable for encapsulating and culturing recombinant sweet protein-producing microbes have already been developed, with additional data collection ongoing. The research plan outlines a one-year completion timeline structured around three phases: library and strain construction, receptor binding assay design, and functional stability screening using FACS. The team is actively seeking partnerships to support bulk protein stability testing, human panel taste testing, and funding for key personnel.
About Harvard University
Harvard University is a comprehensive private research university in Cambridge and Boston, recognized for intensive, cross-disciplinary research and education. Industry engages through an integrated innovation ecosystem with shared core facilities, corporate-sponsored research, and incubator space in Allston. Affiliated teaching hospitals in the Longwood Medical Area enable clinical collaboration and translation, while proximity to Kendall Square places partners in a dense R&D corridor. Research is supported by major federal agencies such as the NIH, NSF, DOE and DARPA, as well as philanthropic and corporate sponsors. A dedicated technology transfer office manages IP, licensing, and startup formation and streamlines agreements for corporate collaborations.
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