DNAzyme-based biosensor technology for selective and real-time detection of potassium ions in biological systems

Background

The ability to monitor potassium ion (K+) dynamics is of critical importance, particularly in the context of cancer research and neurobiology. Potassium ions play a fundamental role in maintaining cellular homeostasis, regulating membrane potential, and influencing processes such as cell proliferation, apoptosis, and immune responses. Disruptions in K+ homeostasis are closely linked to disease progression, including tumor growth, metastasis, and the development of drug resistance. Accurate, real-time detection of K+ fluctuations within living cells is therefore essential for advancing our understanding of disease mechanisms and for developing targeted therapeutic strategies.

However, traditional small-molecule and nanoparticle-based sensors often lack sufficient selectivity, especially in distinguishing K+ from the highly abundant sodium ions (Na+), or have detection ranges that do not align with the high intracellular concentrations of K+ leading to poor sensitivity or saturation. Additionally, these approaches may involve complex synthesis, limited biocompatibility, or high background signals that compromise quantitative accuracy. As a result, researchers are often unable to reliably track K+ dynamics in real time or in the relevant physiological context, hindering both basic research and clinical translation.

Technology description

The technology is a DNAzyme-based fluorescent sensor engineered for the selective detection and real-time imaging of potassium ions (K+). It consists of two DNA strands: a substrate strand containing a single RNA base and a fluorophore-quencher pair, and an enzyme strand with a catalytic loop. In the presence of K+, the enzyme strand catalyzes the cleavage of the RNA base, separating the fluorophore from the quencher and producing a measurable fluorescent signal. The sensor demonstrates over 1000-fold selectivity for K+ over sodium and other relevant ions, making it highly suitable for monitoring physiological intracellular K+ concentrations. Its modular design allows for customization, and it can be delivered into live cells for dynamic imaging of K+ fluctuations, supporting applications in cancer research and cellular physiology.

This technology is differentiated by its exceptional selectivity, sensitivity, and adaptability compared to existing K+ sensors, as it maintains high performance in the physiologically relevant K+ range and minimizes background signals through an inactive control mutant. The DNAzyme core sequences ensure robust K+-dependent activity and minimal cross-reactivity. Its biocompatibility, ease of synthesis, and compatibility with both fluorescence and photoacoustic imaging further set it apart, enabling accurate, quantitative, and real-time monitoring of K+ dynamics in complex biological environments. This platform not only advances fundamental research but also holds promise for diagnostic and therapeutic applications, particularly in oncology where K+ homeostasis is closely linked to tumor progression and drug resistance.

Benefits

Exceptional selectivity for potassium ions with over 1000-fold discrimination against other relevant ions
Detection range and sensitivity optimized for physiological intracellular potassium concentrations
Biocompatible and stable DNA-based sensor suitable for live cell imaging
Simple and customizable synthesis
Robust performance with low background signal
Enables quantitative imaging of potassium dynamics in cancer research
Potential to guide development of improved cancer treatment
Versatile platform adaptable to fluorescence and photoacoustic detection modalities

Commercial applications

Live cell potassium imaging
Cancer progression biomarker analysis
Drug resistance mechanism studies
Ion-channel targeted drug screening
Point-of-care potassium diagnostics

Additional information

This DNAzyme-based fluorescent sensor selectively detects potassium ions. It comprises two DNA strands: a substrate with an RNA base, fluorophore, and quencher, and an enzyme strand with a catalytic loop. K+ binding activates the enzyme, cleaving the RNA base. This separates the fluorophore from the quencher, generating a fluorescent signal for real-time K+ dynamics in living cells, offering high selectivity and physiological detection.