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Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn‐around time and extensive capital equipment. Here, an ultrasensitive and amplification‐free RNA quantification method is demonstrated by integrating CRISPR‐Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR‐powered assay exhibits nearly 1000‐fold lower limit‐of‐detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification‐free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource‐limited settings.

Zika virus (ZIKV) is an increasing global health challenge. There is an urgent need for rapid, low‐cost, and accurate diagnostic tests that can be broadly distributed and applied in pandemic regions. Here, an innovative, adaptable, and rapidly deployable bioplasmonic paper‐based device (BPD) is demonstrated for the detection of ZIKV infection, via quantification of serum anti‐ZIKV‐nonstructural protein 1 (NS1) IgG and IgM. BPD is based on ZIKV‐NS1 protein as a capture element and gold nanorods as plasmonic nanotransducers. The BPD displays excellent sensitivity and selectivity to both anti‐ZIKV‐NS1 IgG and IgM in human serum. In addition, excellent stability of BPDs at room and even elevated temperature for one month is achieved by metal–organic framework (MOF)‐based biopreservation. MOF‐based preservation obviates the need for device refrigeration during transport and storage, thus enabling their use in point‐of‐care and resource‐limited settings for ZIKV surveillance. Furthermore, the versatile design (interchangeable recognition element) of BPDs more generally enables their ready adaptation to diagnose other emerging infectious diseases.

Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are highly promising for on‐chip and point‐of‐care diagnostics. In particular, plasmonic biosensors that rely on artificial antibodies are highly attractive for applications in resource‐limited settings due to the excellent thermal, chemical, and environmental stability of these biorecognition elements. In this work, a universal LSPR response amplification strategy based on the biomineralization of a metal–organic framework (MOF) on the captured analyte proteins is demonstrated. The amplification relies on the differential ability of abiotic recognition elements and captured biomolecules to induce biomineralization of a MOF. The rapid amplification process (less than 10 min) demonstrated here results in nearly 100% higher sensitivity and three times lower limit of detection compared to the innate sensor. The amplification approach can be broadly applied to a wide variety of bioanalytes and can be rapidly implemented in real‐world conditions without compromising the assay time or reusability of the plasmonic biochip.