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Updated: Jun 4, 2026

Design to Implementation Study for Development and Patient Validation of Paper-Based Toehold Switch Diagnostics
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Published on: June 17, 2022

Modular Input-Output Biosensor Design Using De Novo Protein Switches.

James Wang1, Julie Yi-Hsuan Chen1, Chenggang Xi1

  • 1Department of Biomolecular Engineering, University of California, Santa Cruz, California 95064, United States.

ACS Sensors
|June 3, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a versatile biosensor platform called LOCKR. This plug-and-play system efficiently links molecular binding events to detectable signals, enabling sensitive detection of various peptides.

Keywords:
bioassaybiosensorprotein designprotein switchreporter

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Sensor Technology

Background:

  • Protein-based biosensors offer real-time detection with minimal sample preparation, surpassing conventional methods.
  • A significant challenge in biosensor development is effectively translating molecular recognition into a reliable signal output.

Purpose of the Study:

  • To introduce the LOCKR (Ligand-Oriented Combinatorial Kinase-Regulated) platform, a novel plug-and-play strategy for biosensor development.
  • To demonstrate the modularity of the LOCKR platform by enabling interchangeable recognition domains and reporter modules for diverse analyte detection and signal output formats.

Main Methods:

  • The LOCKR platform was designed for modular reconfiguration, allowing for the swapping of recognition domains and reporter modules.
  • The study expanded LOCKR-compatible readouts to include Förster-type resonance energy transfer (FRET) and β-lactamase-based colorimetry, in addition to split luciferase.
  • Computationally designed high-affinity binders were integrated as recognition elements for specific analyte detection.

Main Results:

  • The LOCKR platform successfully enabled direct signal transduction from molecular binding events.
  • Sensitive detection of glucagon, neuropeptide Y, and peptide YY was achieved, with limits of detection in the picomolar range.
  • The platform demonstrated versatility by supporting multiple readout formats, including FRET and colorimetry.

Conclusions:

  • The LOCKR platform provides a flexible and efficient solution for bridging molecular recognition and signal generation in biosensors.
  • This modular approach facilitates the development of tailored biosensors for various user-defined applications.
  • The integration of computationally designed binders enhances the sensitivity and specificity of the developed biosensors.