An optofluidic device is reported in this paper that can highly improve the robustness of surface-enhanced Raman scattering (SERS) detection and provide fingerprint information of proteins with a concentration in the nanogram per liter range within minutes. Moreover, the conformational change of protein can also be obtained using this device. Fabricated by standard photolithography processes, the optofluidic device has a step microfluidic–nanofluidic structure, which provides robust SERS detection. The sensitivity of the device is investigated using insulin and albumin as target analytes at a concentration of 0.9 ng/L. The ability to detect conformational changes of proteins using this technology is also shown by probing these analytes before and after their denaturation.
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