Rapid and selective sampling of IgG from skin in less than 1 min using a high surface area wearable immunoassay patch

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^-2) and array size (4-36 mm²) 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^-2, 36 mm², 140 μm) with a 4.5-fold increase in penetrated surface area compared to our standard MPA design (20,408 proj. cm^-2, 16 mm², 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.