Australian Institute for Bioengineering and Nanotechnology, Delivery of Drugs and Genes Group (D2G2), The University of Queensland, St Lucia, Queensland 4072, Australia; Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, St Lucia, Queensland 4072, Australia.
Australian Institute for Bioengineering and Nanotechnology, Delivery of Drugs and Genes Group (D2G2), The University of Queensland, St Lucia, Queensland 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, St Lucia, Queensland 4072, Australia; Department of Chemical Engineering, Monash University, Clayton, Victoria, 3800, Australia; Australian Infectious Diseases Research Centre, St. Lucia, Queensland, 4067, Australia.
Biomaterials. 2018 Jul;170:49-57. doi: 10.1016/j.biomaterials.2018.03.039. Epub 2018 Mar 22.
Microprojection array (MPA) patches are an attractive approach to selectively capture circulating proteins from the skin with minimal invasiveness for diagnostics at the point-of-care or in the home. A key challenge to develop this technology is to extract sufficient quantities of specific proteins from within the skin to enable high diagnostic sensitivity within a convenient amount of time. To achieve this, we investigated the effect of MPA geometry (i.e. projection density, length and array size) on protein capture. We hypothesised that the penetrated surface area of MPAs is a major determinant of protein capture however it was not known if simultaneously increasing projection density, length and array size is possible without adversely affecting penetration and/or tolerability. We show that increasing the projection density (5000-30,000 proj. cm) and array size (4-36 mm) significantly increases biomarker capture whilst maintaining of a similar level tolerability, which supports previous literature for projection length (40-190 μm). Ultimately, we designed a high surface area MPA (30,000 proj. cm, 36 mm, 140 μm) with a 4.5-fold increase in penetrated surface area compared to our standard MPA design (20,408 proj. cm, 16 mm, 100 μm). The high surface area MPA captured antigen-specific IgG from mice in 30 s with 100% diagnostic sensitivity compared with 10-30 min for previous MPA immunoassay patches, which is over an order of magnitude reduction in wear time. This demonstrates for the first time that MPAs may be used for ultra-rapid (<1 min) protein capture from skin in a time competitive with standard clinical procedures like the needle and lancet, which has broad implications for minimally invasive and point-of-care diagnostics.
微投影阵列 (MPA) 贴片是一种有吸引力的方法，可以选择性地从皮肤中捕获循环蛋白，实现微创，便于在即时护理或家庭环境中进行诊断。开发这项技术的一个关键挑战是从皮肤中提取足够数量的特定蛋白质，以在方便的时间内实现高诊断灵敏度。为了实现这一目标，我们研究了 MPA 几何形状（即投影密度、长度和阵列大小）对蛋白质捕获的影响。我们假设 MPA 的穿透表面积是蛋白质捕获的主要决定因素，但尚不清楚是否可以在不影响穿透和/或耐受性的情况下同时增加投影密度、长度和阵列大小。我们表明，增加投影密度（5000-30000 proj. cm）和阵列大小（4-36 毫米）可显著增加生物标志物捕获量，同时保持相似水平的耐受性，这与之前关于投影长度（40-190 μm）的文献一致。最终，我们设计了一种高表面积 MPA（30000 proj. cm、36 毫米、140 μm），与我们的标准 MPA 设计（20408 proj. cm、16 毫米、100 μm）相比，穿透表面积增加了 4.5 倍。与之前的 MPA 免疫分析贴片相比，高表面积 MPA 在 30 秒内从小鼠中捕获了具有 100%诊断灵敏度的抗原特异性 IgG，而之前的 MPA 免疫分析贴片需要 10-30 分钟，这将佩戴时间缩短了一个数量级。这首次证明 MPA 可用于在与标准临床程序（如针和采血器）竞争的时间内从皮肤中进行超快速（<1 分钟）蛋白质捕获，这对微创和即时护理诊断具有广泛的意义。
