Inappropriate use of veterinary drugs can result in the
presence
of antibiotic residues in animal-derived foods, which is a threat
to human health. A simple yet efficient antibiotic-sensing method
is highly desirable. Programmable DNA amplification circuits have
supplemented robust toolkits for food contaminants monitoring. However,
they currently face limitations in terms of their intricate design
and low signal gain. Herein, we have engineered a robust reciprocal
catalytic DNA (RCD) circuit for highly efficient bioanalysis. The
trigger initiates the cascade hybridization reaction (CHR) to yield
plenty of repeated initiators for activating the rolling circle amplification
(RCA) circuit. Then the RCA-generated numerous reconstituted triggers
can reversely stimulate the CHR circuit. This results in a self-sufficient
supply of numerous initiators and triggers for the successive cross-invasion
of CHR and RCA amplifiers, thus leading to exponential signal amplification
for the highly efficient detection of analytes. With its flexible
programmability and modular features, the RCD amplifier can serve
as a universal toolbox for the high-performance and accurate sensing
of kanamycin in buffer and food samples including milk, honey, and
fish, highlighting its enormous promise for low-abundance contaminant
analysis in foodstuffs.