Lensless Wide-Field Microscopy: Toward Next-Generation Chemical Bioimaging

Lensless imaging offers a new route to substantially alleviate the shackle of space-bandwidth-product (SBP) on conventional optical microscopes, thus high resolution and wide field-of-view (FOV) can be more easily achieved simultaneously. A series of lensless imaging methods have taken their place in chemical bioimaging due to their advantages of wide FOV and low cost. This review discusses the development of sensor-proximal contact, incoherent, holographic, and ptychographic imaging and evaluates their applications across cellular phenotyping, particle and molecular sensing, as well as tissue and in vivo imaging. Particular emphasis is placed on interfacial chemical strategies involving affinity reagents, responsive materials, luminescent reactions, and engineered probes. These approaches convert nanoscale chemical events, which cannot be directly resolved by lensless systems, into amplified and spatially resolved optical signals. By combining chemical signal transduction with large-area imaging, lensless platforms can detect individual cells, particles, and molecular events while simultaneously capturing their temporal dynamics, spatial organization, and collective evolution. This chemistry-centered minireview highlights future opportunities for extracting multiscale spatiotemporal information from complex chemical and biological systems.