NeuroSplice: Portable Multiple Sclerosis Diagnostic Tool
A low-cost, cell-free diagnostic tool that detects a RNA biomarker from blood PBMCs.
The Problem & Our Innovation
The Challenge
Current diagnostic methods for multiple sclerosis often require costly centralized labs and invasive spinal taps that are painful and inaccessible for many patients. These limitations hinder early screening and widen healthcare inequities, despite disease markers like sIL7R isoforms being detectable in blood.
The NeuroSplice Solution
We created NeuroSplice, a low-cost, cell-free diagnostic tool that replaces invasive spinal taps with a simple blood test. Using engineered toehold switches on a portable paper strip, it enables specific, accessible, and affordable early detection of Multiple Sclerosis.
Meet CalUCSF
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Integrated Human Practices & Ethics
Design Integration
We conducted structured interviews with clinical neurologists and community health practitioners to refine the diagnostic target and ensure our deployment strategy addresses global health equity and patient data concerns.
Education & Outreach
Our team developed educational modules for young children that taught how the brain works, why healthy habits keep it strong, and how challenges like MS affect people, while reminding kids of the importance of supporting family and friends with kindness.
Project Pillars
Precision Detection
Engineered toehold switches deliver highly accurate detection with minimal false positives.
Portable & Paper-Based
Freeze-dried, cell-free reactions embedded on a simple, shelf-stable paper strip.
Clear Readout
Flourescence intensity reflects RNA levels, easy to interpret, whether qualitative or quantitative.
Safe by Design
A cell-free system means no living organisms, eliminating escape or biohazard risks.
TXTL Mechanism
This conceptual diagram illustrates the cell-free process: the target RNA binds to the toehold, unzipping it to expose the Ribosome Binding Site (RBS), which initiates the expression of the sfGFP reporter.
Experimental Validation Metrics
Clear ON/OFF Separation
2x Fold Change
sfGFP reporter showed a 2x difference between ON (60,000–70,000 a.u.) and OFF (30,000 a.u.) states across multiple trials (p ≪ 0.0001).
Rapid Detection
4-5 hrs
Fluorescence onset within 4-5 hours in TXTL reactions incubated at 27–32 °C, requiring no thermal cycling.
High Reproducibility
p ≪ 0.0001
Validated over 5 independent runs with consistent ON/OFF kinetics and highly significant reproducibility (p-values as low as 1.43 x 10^-111).
Optimized Reporter
sfGFP
Switching to sfGFP improved brightness, faster maturation, and sharper discrimination compared to earlier chromoprotein reporters.