Hollow Microneedle‐based Plasmonic Sensor for on Patch Detection of Molecules in Dermal Interstitial Fluid

Abstract

Interstitial fluid (ISF) extraction and analysis are challenges that can be tackled by Hollow MicroNeedles (HMNs) technology, overcoming most of the difficulties associated with in situ detection. Herein, a plasmonic transducer, composed of gold nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA) hydrogels, is integrated in the inner cavity of HMNs to detect biomarkers from the ISF‐based point‐of‐care. The wearable HMN‐based patch is used for minimally invasive pierce of the skin. The large swelling capability of the plasmonic transducer allows the uptake of ISF by capillarity. Biotin, as a small model molecule, is efficiently collected in the inner cavity of HMN and its high specificity with the streptavidin is exploited as a validation of the plasmonic nanocomposite functionality embedded within. The recognition of biotin is achieved in dual‐optical mode: the localized surface plasmon resonance (label‐free) and the metal‐enhanced fluorescence (label‐based). Overall, the proposed HMN‐based patch for target sensing in ISF can represent a novel point‐of‐use device for the detection of biomarkers as an alternative to conventional hospital or lab settings to help faster medical decision‐making.

A Review of Recent Advances in Microneedle-Based Sensing within the Dermal ISF That Could Transform Medical Testing

“…3 Polyethylene glycol diacrylate (PEGDA) is chemically stable and is considered by industry to be biologically inert, with a wide range of mechanical properties. 27,28 PEGDA can be polymerized at a very fast rate at room temperature with low energy input in the presence of a UV light source and photoinitiators and has a very high water content and excellent elasticity. 28 Different Ways to Fabricate MNs.…”

“…One of the simplest processing methods is to directly engrave and process the nanocomposite substrate material by UV photolithography (Figure a), , and this direct processing of the substrate material by UV light can be designed for a wide range of shapes, which can result in many integrated MN systems with unique characteristics. ,,, The technique is based on applying a layer of photoresist on the surface and etching the substrate surface with different shapes and heights by UV beams to obtain differently shaped MNs for the preparation of MN integrated systems for ISF detection in conjunction with detection equipment.…”

“…Schematic representation of the processing of different detection MNs: (a) Application of ultraviolet lithography for substrate material engraving. Reproduced from ref . Copyright 2023 Wiley-Blackwell.…”

“…Figure d shows the most commonly used method for mold preparation, 3D printing. − As shown in Figure d, 3D printing involves the design of a template pattern on a computer for printing, after which the designed pattern is sliced, processed and imported into the printer to print the MN template and carry out negative mold preparation. The transfer printing method shown in Figure e is similar to that shown in Figure c, in which the code needed for the experiment is added to the transfer material to obtain the MNs with a specific role. ,, …”

In Situ Tyrosinase Monitoring by Wearable Microneedle Patch toward Clinical Melanoma Screening

“…One fascinating technique for in situ sensing is the utilization of a microneedle (MN) array patch. − Such an MN with hundreds of tiny tips (50–900 μm) can physically pierce the surface layer of the skin, enabling reaching deep skin tissue areas. Recently, MN arrays showed enormous potential and had some success for simple, rapid, continuous, painless, minimally invasive monitoring of various biomarkers on both the skin surface and under the skin, including glucose, alcohol, lactate, pH, nerve agents, and glutamate. − Even so, fewer attempts have been made to develop an MN-based sensor for in situ monitoring of TYR changes so far. Wang and co-workers reported an MN electrochemical sensor, in which the immobilized catechol is rapidly transformed to benzoquinone by TYR, which is detected amperometrically .…”