Early circulating biomarker detection using a wearable microprojection array skin patch

Coffey, Jacob W.; Corrie, Simon R.; Kendall, M. A. F.

doi:10.1016/j.biomaterials.2013.08.078

Cited by 53 publications

(74 citation statements)

References 65 publications

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“…Similar devices reported in the literature include silicon microneedles, produced by reactive ion etching [10,11,12,14], and polycarbonate microneedles [13], produced by compression moulding. PLA microneedles are advantageous because they are inexpensive and simple to fabricate by micromoulding using relatively modest technology.…”

Section: Antibody Immobilisationmentioning

confidence: 86%

“…PLA microneedles are advantageous because they are inexpensive and simple to fabricate by micromoulding using relatively modest technology. Surface activation for PLA microneedles for antibody immobilisation requires fewer steps and much shorter incubation times (2-3 hours) compared to their silicon and polycarbonate counterparts (typically 1-2 days) [10,11,12,13,15]. Consequently, in this study, it was possible to complete antibody immobilisation and blocking of non-specific binding sites within 24 hours.…”

Section: Antibody Immobilisationmentioning

confidence: 87%

“…Previous microneedle-based biomarker extraction studies have necessitated either dilution of the signal in a liquid medium [11,12,13,14,19] or direct quantification of fluorescence on the microneedles [10,15] for detection. Signal dilution is undesirable as it inevitably reduces the sensitivity of the test, especially for biomarkers that are present at very low levels.…”

Section: Benefits and Limitationsmentioning

confidence: 99%

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Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Lau

Williams

2015

Drug Deliv. and Transl. Res.

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Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays.

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Section: Antibody Immobilisationmentioning

confidence: 86%

Section: Antibody Immobilisationmentioning

confidence: 87%

Section: Benefits and Limitationsmentioning

confidence: 99%

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Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Lau

Williams

2015

Drug Deliv. and Transl. Res.

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“…In this application, it is termed microprojection array (MPA), referring to its longer projections (150-250 µm). As biomarker tool, MPAs have been used to capture specific biomarkers from blood and tissue fluids from skin through surface modifications [294,[352][353][354][355]. Thus far, surface-modified MPA have successfully captured OVA-specific IgG [353], NS1 protein [354] and influenza-specific IgG from skin [355].…”

Section: The Nanopatch™mentioning

confidence: 99%

“…As biomarker tool, MPAs have been used to capture specific biomarkers from blood and tissue fluids from skin through surface modifications [294,[352][353][354][355]. Thus far, surface-modified MPA have successfully captured OVA-specific IgG [353], NS1 protein [354] and influenza-specific IgG from skin [355]. Projected into the future, surface-modified MPAs -containing longer projections than the NP -may therefore enable the capture of multiple biomarkers on one patch, with an integrated or separate read-out, providing high-throughput analyses from blood and/ or tissue fluids.…”

Section: The Nanopatch™mentioning

confidence: 99%

Investigation of cell death caused by the Nanopatch™ and its role in vaccine delivery as a physical immune enhancer

Depelsenaire¹

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Since the introduction of vaccines, millions of lives have been saved. Yet, infectious diseases continue to contribute to deaths in underdeveloped countries, with over 2 million children dying per year from preventable diseases such as diphtheria, pertussis and tetanus. Despite the advantages of vaccines, there are also some risks and disadvantages associated with vaccines and their delivery such as the need for medical personnel for administration, refrigeration of the vaccine, disease transmission associated with needles and potential adverse side effects due to adjuvants. While intramuscular and subcutaneous injections are most frequently used for vaccine administration, these sites are poor in antigen-presenting cells. The skin, the largest immunological organ, by contrast contains a dense network of antigen-presenting cells, important in the uptake of antigen and presentation to naive T-cells, and has received increased interest as a target site for vaccine delivery. Intradermal immunisations have achieved significant dose-sparing over conventional immunisation routes. However, using existing needle designs, intradermal injections can be difficult to administer into the thin dermal layer due to the proportionally large scale of the needle. This has led to the development of alternative skin-based delivery methods, such as microneedle arrays.Here, the Nanopatch™ is an array containing 3364 microprojections of ~110 µm in length, which was used to deliver the vaccine into the viable epidermis and dermis of the skin. With an unprecedented >100-fold dose-sparing reported by the Nanopatch™ in comparison to conventional immunisation strategies with an influenza split virion vaccine, the mechanisms behind this skin- The extent of cell death after Nanopatch™ application and intradermal injection was investigated, characterised and quantified by Confocal/ Multiphoton microscopy, Western Blot and flow cytometry. A distinct pattern of dead cells was obtained with significantly higher levels (~65-fold) of cell death in murine ear skin following Nanopatch™ treatment than intradermal injection.ii | P a g e Measured skin cell death was tuneable by changing projection density but not shapes, and was associated with modelled stresses of ≥1 MPa.Immunogenicity studies demonstrated consistently and statistically significantly higher anti-IgG endpoint titres (up to 50-fold higher) in Nanopatch™ than intradermally injected groups after delivery of a split virion influenza vaccine, with a 10-fold dose-sparing effect. Importantly, colocalisation of delivered antigen with both, live and dead cells was necessary for immunogenicity enhancement. Overall, higher inflammatory responses and longer-lasting antigen depot formation were associated with Nanopatch™ immunisations but not with intradermal injections. The findings indicated a correlation between co-localisation of antigen cell death caused by the Nanopatch™ and enhanced immunogenicity with split virion influenza vaccine as model antigen.Collectively, the data presented wi...

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Microneedle Technology

Quinn¹,

Courtenay²,

Kearney³

et al. 2015

Novel Delivery Systems for Transdermal and Intradermal Drug Delivery

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Early circulating biomarker detection using a wearable microprojection array skin patch

Cited by 53 publications

References 65 publications

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Investigation of cell death caused by the Nanopatch™ and its role in vaccine delivery as a physical immune enhancer

Microneedle Technology

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