Transdermal Minimally-Invasive Optical Multiplex Detection of Protein Biomarkers by Microneedles-Embedded Nanopillars Array

Biomarkers detection have become essential in medical diagnostics and early detection of life-threatening diseases. Modern-day medicine relies heavily on painful and invasive tests, the extraction of large volumes of venous blood being the most common tool of biomarker detection. These tests are time-consuming, expansive, and require complex sample manipulations and trained staff. The application of 'intradermal' biosensors utilizing microneedles as a minimally-invasive and pain-free sampling and sensing elements for capillary blood biomarkers detection has gained extensive interest in the past few years as a central point-of-care (POC) detection platform. Herein, we present a new diagnosis paradigm based on vertically-aligned nanopillars array-embedded microneedles sampling-and-detection elements for the direct optical detection and quantification of biomarkers in capillary blood. We present here the first demonstration on the simple fabrication route for the creation of a multidetection-zone silicon nanopillars array, embedded in microneedle elements, followed by their area-selective chemical modification, towards the multiplex intradermal biomarkers detection. The utilization of the rapid and specific antibody-antigen binding, combined with the intrinsically large sensing area created by the nanopillars array, enables the simultaneous efficient ultrafast and highly sensitive intradermal capillary blood sampling and detection of protein biomarkers of clinical relevance, without requiring the extraction of blood samples for the ex-vivo biomarkers analysis. Through preliminary in vitro and in vivo experiments, the direct intradermal in-skin blood extraction-free platform has demonstrated a remarkable sensitivity (low pM) and specificity for the accurate multiplex detection of protein biomarkers in capillary blood.