Hydrogel-Coated Microneedle Arrays for Minimally Invasive Sampling and Sensing of Specific Circulating Nucleic Acids from Skin Interstitial Fluid

Abstract

Minimally-invasive technologies that can sample and detect cell-free nucleic acid biomarkers from liquid biopsies have recently emerged as clinically useful for early diagnosis of a broad range of pathologies, including cancer. Although blood has been so far the most commonly interrogated body fluid, skin interstitial fluid has been mostly overlooked despite containing the same broad variety of molecular biomarkers originating from cells and surrounding blood capillaries. Minimally-invasive technologies have emerged as a method to sample this fluid in a pain-free manner and often take the form of microneedle patches. Herein, we developed microneedles that are coated with an alginate-peptide nucleic acid hybrid material for sequence-specific sampling, isolation and detection of nucleic acid biomarkers from skin interstitial fluid. Characterized by fast sampling kinetics and large sampling capacity (~6.5μL in 2 min), this platform technology also enables for the first time the detection of specific nucleic acid biomarkers either on the patch itself or in solution after light-triggered release from the hydrogel. Considering the emergence of cellfree nucleic acids in bodily fluids as clinically informative biomarkers, platform technologies that can detect them in an automated and minimally invasive fashion have great potential for personalized diagnosis and longitudinal monitoring of patient-specific disease progression.

Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid

“…Zhang et al devised encoded MNs capable of detecting multiple biomarkers such as tumor necrosis factor alpha (TNF‐α), interleukin 1β (IL‐1β), and IL‐6 26. Sulaiman et al developed MNs coated with an alginate‐peptide‐nucleic acid hybrid material for specific nucleic acid sampling and detection 27. Furthermore, the extraction of plant DNA by MNs was demonstrated for rapid detection of plant diseases 28…”

Advances in the Formulations of Microneedles for Manifold Biomedical Applications

“…In order to simplify postquantification of biomarkers, Zhang et al integrated the hydrogel MNs with photonic crystal barcodes, which enabled direct quantification of the biomarkers via the fluorescence of the barcodes . Moreover, Al Sulaiman et al coated the solid MNs with a layer of hydrogel which covalently connected with bespoke peptide nucleic acid (PNA) probes via a photocleavable linker . When MNs were in contact with the solution containing DNA, the DNA sequence of interest diffused into hydrogel matrix and hybridized to the probes to form the PNA:DNA complex.…”

“…When MNs were in contact with the solution containing DNA, the DNA sequence of interest diffused into hydrogel matrix and hybridized to the probes to form the PNA:DNA complex. The nonspecific DNA could be removed from MNs by simple washing ( Figure ) . There were two ways for quantification or analysis of these captured DNA.…”

“…B) Schematic of the generic protocol for MN sampling of target biomarker (red) and purification to remove nontarget sequences (green). Reproduced with permission . Copyright 2019, American Chemical Society.…”

Engineered Microneedles for Interstitial Fluid Cell‐Free DNA Capture and Sensing Using Iontophoretic Dual‐Extraction Wearable Patch

“…Although state‐of‐the‐art MNs have greatly promoted sample extraction, [ 10–12 ] some limitations in the isolation of biomolecules exist. Consequently, some enhanced MN platforms approached these tedious problems by means of laser illumination, [ 13 ] multiple photonic crystal barcodes, [ 14 ] hydrogels, [ 15–17 ] and near infrared quantum dots. [ 18 ] Sulaiman et al first reported ultrafast MNs based on an alginate‐peptide hydrogel for sequence‐specific isolation, extraction, and detection of microRNA within 2 min.…”