Signal-amplifying Biohybrid Material Circuits for CRISPR/Cas-based single-stranded RNA Detection

Abstract

The functional integration of biological switches with synthetic buildingblocks enables the design of modular, stimulus-responsive biohybridmaterials. By connecting the individual modules via diffusible signals,information-processing circuits can be designed. Such systems are, however,mostly limited to respond to either small molecules, proteins, or optical inputthus limiting the sensing and application scope of the material circuits. Here,a highly modular biohybrid material is design based on CRISPR/Cas13a totranslate arbitrary single-stranded RNAs into a biomolecular material response.This system exemplified by the development of a cascade of communicatingmaterials that can detect the tumor biomarker microRNA miR19b in patientsamples or sequences specific for SARS-CoV. Specificity of the system is furtherdemonstrated by discriminating between input miRNA sequences with single-nucleotide differences. To quantitatively understand information processing inthe materials cascade, a mathematical model is developed. The model is usedto guide systems design for enhancing signal amplification functionality of theoverall materials system. The newly designed modular materials can be usedto interface desired RNA input with stimulus-responsive and information-processing materials for building point-of-care suitable sensors as well as multi-input diagnostic systems with integrated data processing and interpretation.