Programmable artificial cells for point-of-care nucleic acid detection

Overview

This research proposes programmable artificial cells built on a microfluidic chip that leverage toehold switch technology for the highly sensitive and specific point-of-care (POC) detection of nucleic acids. The artificial cells are designed with hierarchical compartments that mimic natural cellular processes, enabling the integration and sequential control of transcription and translation within a single, controllable platform.

By fusing synthetic biology with microfluidic technology, the approach aims to overcome limitations in current nucleic acid detection methods, delivering improved accuracy, efficiency, and speed. Potential applications span medical diagnostics, environmental monitoring, and biotechnological research, offering a novel diagnostic tool capable of detecting a wide range of sequences with high specificity.

Technical specifications

Core technology components:

• Programmable artificial cells engineered with hierarchical compartments that replicate natural intracellular biochemical processes
• Toehold switch technology integrated for specific and sensitive detection of target nucleic acid sequences
• Microfluidic chip architecture enabling controlled, sequential execution of transcription, translation, and post-translational modifications
• Compartmentalized design with separate functional zones for each stage of the central dogma, allowing precise regulation of biomolecular processes

Key capabilities demonstrated in preliminary work:

• Successful execution of complex biomolecular processes within an artificial cell-on-a-chip format
• Production of post-translationally modified proteins, including ubiquitinated α-synuclein (linked to Parkinson's disease), as a proof-of-concept for cellular mimicry
• Specific and sensitive nucleic acid detection enabled by toehold switch advancements

Technology readiness level

The technology is currently at an early-to-mid stage of development. Preliminary validation has been achieved through prior demonstrations of artificial cell-on-a-chip functionality and toehold switch-based nucleic acid detection. The research plan is structured in three stages: design and fabrication of the programmable artificial cells with integrated compartments and toehold switches; testing and optimization to evaluate detection accuracy across various nucleic acid sequences; and application validation through comparative studies against standard point-of-care diagnostic methods using clinically relevant targets. The platform is advancing toward prototype development with clear pathways to clinical and field validation.