The functional integration of biological switches with synthetic building blocks enables the design of modular, stimulus-responsive biohybrid materials. 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 input thus limiting the sensing and application scope of the material circuits. Here, we design a highly modular biohybrid material based on CRISPR-Cas13a to translate arbitrary single-stranded RNAs into a biomolecular material response. We exemplify this system by the development of a cascade of communicating materials that can detect the tumor biomarker microRNA miR19b in patient samples or sequences specific for COVID-19. Specificity of the system is further demonstrated by discriminating between input miRNA sequences with single-nucleotide differences. To quantitatively understand information processing in the materials cascade, we developed a mathematical model. The model was used to guide systems design for enhancing signal amplification functionality of the overall materials system. The newly designed modular materials can be used to 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.

The authors have declared no competing interest.

European Union (ERC, STEADY, 101053857) German Research Foundation (DFG) under Germany's Excellence Strategy CIBSS, EXC2189, Project ID: 390939984 and under the Excellence Initiative of the German Federal and State Governments BIOSS, EXC294, by the German Ministry of Education and Research (BMBF) through LiSyM Cancer (Grant No. 031L0256G) in part by the Ministry for Science, Research and Arts of the state of Baden-Wuerttemberg by the state of Baden-Wuerttemberg through bwHPC Bundesministerium fuer Bildung und Forschung (BMBF) under grant number 13GW0493 (MERGE)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Collection of plasma samples from patients was approved by the Ethic commission of the Medical university of Vienna. The title of the Ethic vote is “Bestimmung von Biomarkern in Tumorgewebe, Liquor und Blut bei Patienten mit Hirn- und Rückenmarkstumoren” (No. 1244/2016).

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All data produced in the present study are available upon reasonable request to the authors