Microbiopsy engineered for minimally invasive and suture-free sub-millimetre skin sampling

Abstract

We describe the development of a sub-millimetre skin punch biopsy device for painless and suture-free skin sampling for molecular diagnosis and research. Conventional skin punch biopsies range from 2-4 mm in diameter. Local anaesthesia is required and sutures are usually used to close the wound. Our microbiopsy is 0.50 mm wide and 0.20 mm thick. The microbiopsy device is fabricated from three stacked medical grade stainless steel plates tapered to a point and contains a chamber within the centre plate to collect the skin sample. We observed that the application of this device resulted in a 0.21 ± 0.04 mm wide puncture site in volunteer skin using reflectance confocal microscopy. Histological sections from microbiopsied skin revealed 0.22 ± 0.12 mm wide and 0.26 ± 0.09 mm deep puncture sites. Longitudinal observation in microbiopsied volunteers showed that the wound closed within 1 day and was not visible after 7 days. Reflectance confocal microscope images from these same sites showed the formation of a tiny crust that resolved by 3 weeks and was completely undetectable by the naked eye. The design parameters of the device were optimised for molecular analysis using sampled DNA mass as the primary end point in volunteer studies. Finally, total RNA was characterized. The optimised device extracted 5.9 ± 3.4 ng DNA and 9.0 ± 10.1 ng RNA. We foresee that minimally invasive molecular sampling will play an increasingly significant role in diagnostic dermatology and skin research.

Dysplastic/Clark naevus in the era of molecular pathology

“…Development and employment of minimally invasive techniques such as sub‐millimetre skin biopsies to obtain genomic material for molecular studies would be of great value in evaluation of clinically difficult lesions . Another promising approach is non‐invasive tape stripping of stratum corneum to isolate RNA to evaluate the gene expression profile of suspicious lesions.…”

Advances of the skin microbiopsy for blood and skin sampling with streamlined handling and fabrication settings

“…Early microneedle designs usually possessed a solid body and were primarily designed for cosmetic or therapeutic purposes, such as drug delivery 33 . Recent advances in rapid prototyping techniques, for example 3D printing and laser cutting, has enabled microsampling with microneedles for clinical research purposes 34,35 .…”

“…Another major limitation is that these designs often require the use of some advanced fabrication technologies and therefore are not scalable in most cases 49,50 . In contrast, Lin et al reported an alternative type of hollow microneedle, the skin microbiopsy, that was fabricated with relatively low-tech equipment, such as a laser cutter, for skin sampling 34 . In the study, the skin microbiopsy was fabricated with three layers of medicalgrade steel sheet ( Fig.…”

“…7a & b). The skin microbiopsy penetrated the skin approximately 500 µm deep, and the channel in the middle of the microneedle was able to sample tiny pieces of skin tissue like a claw 34 (Fig. 7c).…”

“…Although the absorbent microneedle does not offer the continuous monitoring function like the hollow microneedle, the fabrication process is usually much simpler, and thus the cost of the device is much lower comparatively. For the case of the absorbent microbiopsy, the fabrication process only involved the use of laser cutting and low-cost materials, such as filter paper and stainless-steel sheet 34,54 . Furthermore, the absorbent microneedle has the potential to facilitate clinical research by reducing the use of reagents and the use of animals when compared to other conventional sampling approaches.…”