A “hot Spot”-Enhanced paper lateral flow assay for ultrasensitive detection of traumatic brain injury biomarker S-100β in blood plasma

Currently colorimetric paper lateral flow strips (PLFS) encounter two major limitations, that is, low sensitivity and severe interference from complex sample matrices such as blood. These shortcomings limit their application in detection of low-concentration analytes in complex samples. To solve these problems, a PLFS has been developed by utilizing surface-enhanced Raman scattering (SERS) for sensing signal transduction. In particular, a hierarchical three-dimensional nanostructure has been designed to create “hot spots”, which can significantly amplify the SERS sensing signal, leading to high sensitivity. As a result, this PLFS has demonstrated a limit of detection (LOD) of 5.0 pg mL−1 toward detection of S-100β, a traumatic brain injury (TBI) protein biomarker in blood plasma. The PLFS has been successfully used for rapid measurement of S-100β in clinical TBI patient samples taken in the emergency department. Availability of PLFS for blood testing would shift the paradigm of TBI patient management and clinical outcome in emergency departments. It is expected that this type of PLFS can be adapted for rapid detection of various human diseases due to its capability of measuring a low level of protein blood biomarkers in complex human fluids. •A paper biosensor for the detection of protein biomarker in blood plasma is proposed.•A hierarchical 3D plasmonic nanostructure is developed to improve detection sensitivity.•A two-order of magnitude improvement in detection sensitivity is obtained.•Test results from the proposed sensor are comparable to those by the standard ELISA in clinical samples.•The proposed sensor provides guidance for rational design of highly sensitive and anti-interference POC devices.