Nanophotonic resonators can confine light to deep-subwavelength volumes with highly enhanced near-field intensity and therefore are widely used for surface-enhanced infrared absorption spectroscopy in various molecular sensing applications. The enhanced signal is mainly contributed by molecules in photonic hot spots, which are regions of a nanophotonic structure with high-field intensity. Therefore, delivery of the majority of, if not all, analyte molecules to hot spots is crucial for fully utilizing the sensing capability of an optical sensor. However, for most optical sensors, simple and straightforward methods of introducing an aqueous analyte to the device, such as applying droplets or spin-coating, cannot achieve targeted delivery of analyte molecules to hot spots. Instead, analyte molecules are usually distributed across the entire device surface, so the majority of the molecules do not experience enhanced field intensity. Here, we present a nanophotonic sensor design with passive molecule trapping functionality. When an analyte solution droplet is introduced to the sensor surface and gradually evaporates, the device structure can effectively trap most precipitated analyte molecules in its hot spots, significantly enhancing the sensor spectral response and sensitivity performance. Specifically, our sensors produce a reflection change of a few percentage points in response to trace amounts of the amino-acid proline or glucose precipitate with a picogram-level mass, which is significantly less than the mass of a molecular monolayer covering the same measurement area. The demonstrated strategy for designing optical sensor structures may also be applied to sensing nano-particles such as exosomes, viruses, and quantum dots., Photonic sensors: trapping analytes by digging into nano-trenches An innovative sensor can make it easier to use infrared light for label-free, picogram-scale detection of amino acids and other molecules. Photonic sensors avoid the need for large quantities of analytes by using nanoscale gap structures to trap targets and subject them to ultrahigh optical fields. Peter Liu and colleagues at the State University of New York at Buffalo in the United States have developed a microchip that naturally drives molecules into nanoscale gap regions. The team fabricated arrays where aluminum ribbons overhang narrower strips of insulating crystals. When a drop of test solution is placed onto the chip and left to evaporate, surface tension creates concave profiles that concentrate molecules under the aluminum layers. The resonant frequencies within this device’s “nano-trenches” can be tuned to specific molecular targets by tweaking the array’s geometric parameters.