Aptamer-linked photonic crystal hydrogel sensor for rapid point-of-care detection of human immuno-deficiency virus-1 (HIV-1). Journal of pharmaceutical and biomedical analysis The detection of the human immunodeficiency virus-1 (HIV) at an early stage is vital and could be realized through its cell surface glycoprotein-120 (gp120) without virus preprocessing. Here, we present an ssDNA-aptamer-linked photonic crystal (APC) hydrogel sensor for HIV detection which is comprised of photonic crystals (PCs) made of polystyrene nanoparticles embedded in the polyacrylamide hydrogel. ssDNA aptamers specific for gp120 are crosslinked in the hydrogel which can selectively bind to gp120 by hydrogen bonding increasing the PCs particle spacing and swelling of the hydrogel. The binding response can be visually monitored as a color change due to the diffraction of light from PCs and can eventually be measured (1-1000 ng mL of gp120) and 10 to 10 VP mL of HIV by the Debye's ring diameter or a UV/Vis spectrometer. APC-hydrogel can be regenerated by Tris-HCl and EDTA washing buffer system. The sensor demonstrates LOD of 7.1 ± 1.55 ng mL for gp120 and 4 VP mL for the whole HIV, a rapid response of 5 min, reusability up to 70 % (in fifth use), and recovery of 95.4 ± 0.1 % to 99.0 ± 0.2 % in plasma samples. The sensor is cost-effect and stable compared to antibody-based sensors and can be utilized to develop point-of-care testing (POCT) devices for HIV diagnosis. 10.1016/j.jpba.2022.115104