Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE 2 RD), which addresses all these impediments on a single platform. The NE 2 RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE 2 RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE 2 RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the pointof-care or primary care settings and at patients' homes.iosensing platforms have enabled various applications in different fields of clinical medicine such as biomarker/drug discovery and initiation and monitoring of therapy (1-3). However, material cost, accessibility, ease of operation, lack of portability, and complexity in readout remain major challenges for developing robust diagnostic assays (SI Appendix, Table S1). Recent advances in nanotechnology and biosensing have created new avenues to address these issues (4-9). Technically, they have provided integration of high-throughput sampling with readout systems for quantitative detection of disease-specific biotargets. Therefore, they have demonstrated great potential to revolutionize medical diagnostics. However, from a clinical and technological perspective, existing platforms still face several challenges. First, lengthy assay time hinders physicians from making early clinical decisions. Second, examining clinical samples with diverse pH range, ionic content, and ionic strength requires
SignificanceBiosensing technologies have significant impact on medical diagnostics but difficulties in the handling of complex biospecimens, portability, and nonlinearity in dynamic detection range present considerable technical bottlenecks in their tran...