title: Dynamic application of microprojection arrays to skin induces circulating protein extravasation for enhanced biomarker capture and detection.
abstract: Surface modified microprojection arrays are a needle-free alternative to capture circulating biomarkers from the skin in vivo for diagnosis. The concentration and turnover of biomarkers in the interstitial fluid, however, may limit the amount of biomarker that can be accessed by microprojection arrays and ultimately their capture efficiency. Here we report that microprojection array insertion induces protein extravasation from blood vessels and increases the concentration of biomarkers in skin, which can synergistically improve biomarker capture. Regions of blood vessels in skin were identified in the upper dermis and subcutaneous tissue by multi-photon microscopy. Insertion of microprojection array designs with varying projection length (40-190 μm), density (5000-20,408 proj.cm(-2)) and array size (4-36 mm(2)) did not affect the degree of extravasation. Furthermore, the location of extravasated protein did not correlate with projection penetration to these highly vascularised regions, suggesting extravasation was not caused by direct puncture of blood vessels. Biomarker extravasation was also induced by dynamic application of flat control surfaces, and varied with the impact velocity, further supporting this conclusion. The extravasated protein distribution correlated well with regions of high mechanical stress generated during insertion, quantified by finite element models. Using this approach to induce extravasation prior to microprojection array-based biomarker capture, anti-influenza IgG was captured within a 2 min application time, demonstrating that extravasation can lead to rapid biomarker sampling and significantly improved microprojection array capture efficiency. These results have broad implications for the development of transdermal devices that deliver to and sample from the skin.
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; University of Queensland, ARC Centre of Excellence in Convergent Bio-NanoScience and Technology, Brisbane, Queensland 4072, Australia.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Coffey
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; University of Queensland, ARC Centre of Excellence in Convergent Bio-NanoScience and Technology, Brisbane, Queensland 4072, Australia.
authors.forename: Stefano C
authors.initials: SC
authors.lastname: Meliga
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; University of Queensland, ARC Centre of Excellence in Convergent Bio-NanoScience and Technology, Brisbane, Queensland 4072, Australia; University of Queensland, Australian Infectious Diseases Research Centre, Brisbane, Queensland 4072, Australia.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Corrie
authors.affiliation: University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland 4072, Australia; University of Queensland, ARC Centre of Excellence in Convergent Bio-NanoScience and Technology, Brisbane, Queensland 4072, Australia; University of Queensland, Australian Infectious Diseases Research Centre, Brisbane, Queensland 4072, Australia; University of Queensland, Faculty of Medicine and Biomedical Sciences, Brisbane, Queensland 4072, Australia. Electronic address: m.kendall@uq.edu.au.
authors.forename: Mark A F
authors.initials: MAF
authors.lastname: Kendall
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D019937:Diagnostic Techniques and Procedures / Q000295:instrumentation*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism*; D005260:Female; D008807:Mice, Inbred BALB C; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D000418:Albumins; D015415:Biomarkers
keywords: Biomarkers; Diagnosis; Extravasation; Microneedles; Sampling; Skin