Intracellular Signal Amplification for Ultrasensitive Detection and Imaging: Progress, Challenges, and Opportunities

Abstract

AbstractDisease signaling molecules and biomarkers are important in biosensing and biomedicine, and their ultra‐sensitive detection and imaging are critical in medical diagnosis. However, most biomarkers have low levels of expression in cells and are easily degraded; therefore, they cannot be accurately detected in real time by conventional amplification methods, which are typically confined to cell lysates. To achieve highly sensitive detection of intracellular low‐abundance molecules, extensive efforts have been devoted to the development of in situ signal amplification techniques. This review tracks the development of recent advances in in situ signal amplification strategies, and systematically summarizes the advantages and disadvantages of enzymatic and non‐enzymatic amplification techniques for detecting and tracing intracellular targets. Further, perspectives, challenges, and opportunities for intracellular signal amplification are discussed to promote its adoption for in situ signal amplification in clinical settings and to provide new insights into signaling molecules and biomarkers in cellular functions and associated diseases.