Colorimetric sensing offers instant reporting via visible signals. Versus labor-intensive and instrument-dependent detection methods, colorimetric sensors present advantages including short acquisition time, high throughput screening, low cost, portability, and a user-friendly approach. These advantages have driven substantial growth in colorimetric sensors, particularly in point-of-care (POC) diagnostics. Rapid progress in nanotechnology, materials science, microfluidics technology, biomarker discovery, digital technology, and signal pattern analysis has led to a variety of colorimetric reagents and detection mechanisms, which are fundamental to advance colorimetric sensing applications. This review first summarizes the basic components (e.g., color reagents, recognition interactions, and sampling procedures) in the design of a colorimetric sensing system. It then presents the rationale design and typical examples of POC devices, e.g., lateral flow devices, microfluidic paper-based analytical devices, and wearable sensing devices. Two highlighted colorimetric formats are discussed: combinational and activatable systems based on the sensor-array and lock-and-key mechanisms, respectively. Case discussions in colorimetric assays are organized by the analyte identities. Finally, the review presents challenges and perspectives for the design and development of colorimetric detection schemes as well as applications. The goal of this review is to provide a foundational resource for developing colorimetric systems and underscoring the colorants and mechanisms that facilitate the continuing evolution of POC sensors.

The transmission of SARS‐CoV‐2 coronavirus has led to the COVID‐19 pandemic. Nucleic acid testing while specific has limitations for mass surveillance. One alternative is the main protease (M^pro) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect M^pro via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C‐/N‐terminus to exploit the specific recognition by M^pro. Autolytic cleavage releases a positively charged moiety that assembles the nanoparticles with rapid color changes (t<10 min). We determine a limit of detection for M^pro in breath condensate matrices <10 nM. We further assayed ten COVID‐negative subjects and found no false‐positive result. In the light of simplicity, our test for viral protease is not limited to an equipped laboratory, but also is amenable to integrating as portable point‐of‐care devices including those on face‐coverings.