In April 2022, Trajan Scientific and Medical licensed a novel skin microbiopsy™ technology, dubbed Harpera™, developed by the University of Queensland (UQ). This technology, crafted by Prof. Tarl W. Prow, Prof. Peter Soyer, and Dr. Alexander Bernard Ansaldo, offers a less invasive alternative for diagnosing inflammatory skin diseases, skin cancers, and more.
Initially envisioned for studying tumor and inflammation markers via less invasive means, Harpera's non-surgical biopsy method has in recent times shown its applicability across various dermatological and cosmetological areas, including parasitic skin infections, wound healing kinetics, pre-clinical studies, and identification of targeted skin biomarkers to customize dermatology or cosmetology treatments. The devices simple design presents a skin biopsy method easily adoptable by a wider range of healthcare professionals, like general practitioners and nurses.
In the area of skin cancer monitoring, this gentler punch biopsy may enable more frequent skin biopsies needed for longitudinal tracking of a patient's skin cancer status over time without requiring them to endure painful surgical procedures. The Harpera™ Microbiopsy™ Punch facilitates minimally invasive biopsies for more frequent monitoring by healthcare professionals.
According to Australia's Department of Health and Ageing, Australia and New Zealand have the highest skin cancer incidence and mortality rates in the world. Furthermore, according to the American Cancer Society, there are approximately 5.4 million basal and squamous cases diagnosed in the United States each year, and 20% of these are squamous cell carcinoma.
It is estimated that one Australian is diagnosed with melanoma every 30 minutes. A risk factor to developing squamous cell carcinoma is the formation of precancerous actinic keratosis (AK), which should be identified and treated early to prevent progression.
The two most common tests used to diagnose skin cancer are imaging, such as computer tomography (CT) or Magnetic Resonance Imaging (MRI), and skin biopsy.
There are currently three popular techniques for skin biopsy: excisional biopsy, where the whole growth is removed; shave biopsy, where the physician shaves the top layer of the skin; and punch biopsy, where the physician takes a 2-5 mm skin sample. In all cases, biopsy samples are sent to a pathology laboratory for histological analysis.
However, rather than being designed to pierce the skin to obtain a blood microsample, the Harpera device was designed as a punch biopsy alternative that could collect a skin sample with a width of 0.25 mm and penetration depth of up to 1.2mm.
This is quite small compared to the 2-5mm diameter size of a traditional punch biopsy. The “lancet” element of the Microbiopsy device was made up of three layers. Each layer was manufactured using 0.05mm thick medical grade stainless steel, shaped using laser cutting. It was housed in a spring-loaded applicator.
The middle layer of the needle was either flat (like the outer layers) or forked at its terminus to create a sample collection chamber.
The conventional approach to collecting a skin biopsy sample to identify skin cancer or another skin condition has several disadvantages and limitations:
With consent, Microbiopsy skin samples were collected multiple times from a group of 20 healthy volunteers or ex vivo from excised actinic keratosis (AK) lesions from conventional biopsies of patient samples. The samples were appropriately stored in PBS and or in RNALater® prior to analysis. Microscopy of the wound site was conducted to monitor healing. RNA and DNA sequencing were conducted to evaluate device performance.
Chamber width was also evaluated by microscopy. Upon imaging the blades, best performance of collections from all 20 volunteers were achieved with a chamber width of 0.15 mm. Using reflectance confocal microscopy, both skin strata were observed from imaging and around 1634 nuclei were observed from the microbiopsies.
In terms of DNA collection, the 0.15 mm chamber yielded the highest amount of DNA (5.9 ±3.4ng) although there was no significant difference when channel widths of 0-0.20 mm were employed. Indeed, the yield of DNA when the sampler had no chamber was 4.5 ±1.4ng. Furthermore, the researchers observed that increasing the surface roughness of the microbiopsy would lead to higher but more variable DNA yield.
The optimal velocity of the device was evaluated, and 16.6 m/s (p<0.0001) was found to be optimal (6.0 ±3.0 ng). When slower velocities were employed, DNA yield significantly dropped to the point that at less than 9.2 m/s, negligible amounts of DNA were collected. Faster velocities (up to 20.2 m/s was tested) did not yield any further DNA.
Pain upon sampling was also assessed and all volunteers scored 0 out of 10 at 5 min after final microbiopsy collection. It must be noted that pain did increase with increasing sampling velocities. When a 0.15 mm channel at 20.2 m/s was used, the average pain score was 1.5 ± 1.1, which is still considered a low pain value.
Reflectance confocal microscopy was also employed to image the application site and the puncture sites, which were found to measure around 0.10 x 0.5mm. Local erythema was observed, and this lasted for up to 24 hours. Afterwards, this was not visible to the naked eye.
The RNA from conventional vs Microbiopsies of AK samples were compared and gave comparable (RNA Integrity) RIN scores (conventional biopsy RIN = 6.5, Microbiopsy, RIN = 5.10). Furthermore, observation of the gels showed both similarities and differences in the band patterns from the RIN experiment. It was concluded that this may have been due to the differences in sample size.
The group then conducted whole transcriptome amplification for the microbiopsy samples and for a representative amount of skin as a control. They observed a 2000-fold amplification and cDNAs for both, which resulted in similar quality. Moreover, they then performed PCR (Polymerase Chain Reaction) to amplify human beta-actin (often used as an endogenous housekeeping gene mRNA) in the samples. Identical bands on the gel electrophoresis plate were observed for both sample types.
Because this device allows for multiple micro-biopsies to be collected from the same subject, the researchers anticipate that Harpera could be used in future for routine procedures to obtain molecular data of skin lesions.
As analytical technology becomes progressively more sensitive, the amount of biological material needed for analysis in research becomes smaller, where tiny microsamples are sufficient for gathering study data.
This remote research approach negated the need for study participants to attend in-clinic phlebotomy procedures for blood draws. Innovations such as the Microbiopsy device evaluated by LL Lin et al in the study paper summarized here demonstrate how the concept of a disposable lancet can be repurposed in a device to reliably collect skin samples.
It is hoped that this new Microbiopsy device has the potential to measure molecular tumor markers, allowing researchers to understand more fully the pathology of the transition of AK lesions into full blown squamous skin cancer.
Neoteryx, the microsampling brand of Trajan, is now working to bring Microbiopsy to market. The Harpera Microbiopsy Punch is currently in development and available as an Investigational Use Only (IUO) tool and aims to support researchers in:
This article was summarized for our readers by James Rudge, PhD, Technical Director, and edited by Florian Lapierre, PhD, Product Director at Neoteryx, the microsampling brand of Trajan Scientific and Medical. This is curated content. To learn more about the important research outlined in this blog, visit the original paper published in F1000 Research.
Related Reading: https://www.neoteryx.com/microsampling-blog/harpera-publication-list
Image Credits: Neoteryx, Trajan