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Harpera, a new skin microbiopsy tool for dermatological research

In April 2022, Trajan Scientific and Medical (Trajan) announced it had licensed a skin microbiopsy technology invented by researchers at the University of Queensland (UQ) to commercialize it.

One of the primary goals for development of this new microbiopsy technology, which Trajan named Harpera, was to provide a minimally invasive sampling tool for research into inflammatory skin diseases and skin cancers. The UQ inventors, Prof. Tarl W. Prow, Prof. Peter Soyer, Dr. Alexander Bernard Ansaldo, hoped that this innovative technology could, in many cases, replace the more invasive skin biopsy technologies currently available for analyzing skin conditions.

Since their early prototypes of the new microbiopsy tool were created, other potential applications for it have emerged, including parasitic skin infections, wound healing kinetics, pre-clinical studies, and identification of targeted skin biomarkers to customize dermatology or cosmetology treatments.

The Field of Skin Biopsy Is Ripe for New Technology with a Personalized Approach

the harpera tool on a white surface.

The inventors at the UQ knew that there was potential in the skin biopsy market for a small, portable microbiopsy tool.

With advancements in omics technologies (which often require far smaller sample sizes for accurate bioanalysis), they hoped that tumor and inflammation markers taken from smaller, less invasive skin microbiopsies might replace the more invasive traditional biopsies.

Less invasive biopsy approaches would enable more personalized longitudinal monitoring of skin conditions.

The UQ inventors hoped their tool could be used easily and effectively by a wider range of healthcare professionals, including general practitioners and nurses. The inventors also aimed at creating a tool that could deliver a pain-free skin biopsy experience, even in sensitive areas like the face.

In the area of skin cancer monitoring, they hypothesized that this gentler tool could enable the 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.

Development of a Microbiopsy Sampling Tool to Overcome Biopsy Limitations

Harpera 2024_IM_4182-1A study paper by LL Lin et al, published in the July 2013 edition of F1000 Research evaluated the form and function of this new microbiopsy (MB) tool, which is similar to a disposable blood lancet.

However, rather than being designed to pierce the skin to obtain a blood microsample, the MB tool 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 MB tool 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 Need to Improve Skin Cancer Identification & Tracking: A Potentially Preventable Disease

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.

a doctor inspects a womens neck for skin cancer.

It is estimated that one Australian is diagnosed with melanoma every 30 minutes. 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.

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.

Disadvantages of Current Skin Biopsy Approaches & Technologies

The conventional approach to collecting a skin biopsy sample to identify skin cancer or another skin condition has several disadvantages and limitations. First, after a subjective visual assessment, a skin biopsy must be performed by an expert dermatologist, who will use several tools and technologies to surgically extract the specimen.

Second, the biopsy procedure typically occurs after the skin cancer has already developed enough to be visually identified. Third, current biopsy procedures are invasive and painful, resulting in scarring in most cases.

Unfortunately, current skin biopsy protocols have been established to fit laboratory requirements for histological examination of specimens, rather than the needs of dermatologists or the comfort of patients.

Another limitation is that current histopathology measurements typically have low accuracy rates and can be considered subjective.

Characterizing the Form and Function of the New Microbiopsy Device

  • With consent, MB 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.

Microbiopsy Study Authors’ Conclusions

  • Although histopathology from traditional biopsies allows for accurate diagnosis, molecular diagnostics (both DNA and RNA) allows for detection of molecular markers. The MB device has the potential to screen lesions for disease markers in discovery research. It also has the potential to facilitate longitudinal studies from lesions, without destroying the lesion.

  • The RIN scores matched those of shave biopsies, although the authors highlighted that in some cases these were too low for whole transcriptome approaches.

  • Procedures using this MB device do not need anesthesia, or sutures, or the setup for a minor surgery like a conventional skin biopsy.

  • Because this tool allows for multiple microbiopsies to be collected from the same subject, the researchers anticipate that this tool could be used in future for routine procedures to obtain molecular data of skin lesions.

Neoteryx Comments

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.

Further, microsampling tools like the new Harpera microbiopsy device described here can be conveniently used by a wide range of healthcare personnel, or even laypeople, with some basic training.

The potential for remote microsampling devices that can support a wide range of applications is increasing. Indeed, we saw a revolution in blood microsampling in 2020, when around 10,000 sample collection kits containing 10 µL Mitra® devices were sent to volunteers at home for a remote serosurveillance study of COVID-19.

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 tool to reliably collect skin samples.

It is hoped that this new microbiopsy tool 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.

Next Steps for the Harpera Microbiopsy Tool

Neoteryx, the microsampling brand of Trajan, is now working to bring this new microbiopsy technology to market. The Harpera microbiopsy tool is currently available for research use only (RUO) and aims to support researchers in:

  • Applying a low-risk, minimally invasive collection process, without the need for anesthesia or sutures
  • Increasing compliance from participant by providing an option for rapid, painless specimen collection, even in cosmetically sensitive areas (e.g., face, neck)
  • Enabling flexible longitudinal monitoring through more frequent sampling over time
  • Providing reliable, high-quality skin specimens for various type of biomarker assays (ELISA, qPCR, Sanger sequencing, Live cells assays, etc.)

Visit our Harpera webpage and schedule a meeting with a microsampling specialist to learn more.


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

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