We have open-sourced the design files for Otto, the Franz diffusion cell autosampler that we built to automate skin permeation studies. This means we’re sharing the 3D-printable models with the world, for free. Anyone may print, modify and share these files with others — with attribution. The files are released under the CC BY 4.0 licence.
Abdelghany TM, Vo N, Vukajlovic D, Smith E, Wong JZ, Jackson E, Hilkens CMU, Lau WM, Ng KW, Novakovic K. Engineering and in vitro evaluation of semi-dissolving, hydrogel-forming polymeric microneedles for sustained-release drug delivery. Int J Pharm. 2025:125932. https://doi.org/10.1016/j.ijpharm.2025.125932
In our latest paper, we describe a microneedle formulation that utilises two polymeric domains: a soluble one and an insoluble one. The insoluble domain is chemically crosslinked and traps the soluble polymer, along with the drug, within it. This combination creates a microneedle array patch that can release a drug for over 2 months.
It can contain a significantly larger dose than microneedles where the drug is contained within the microneedle tips only (e.g., detachable microneedles). The drug reservoir in the backplate makes this possible to support extended release. It uses one-pot synthesis, a mild hydroalcoholic solvent system and mild temperatures to aid manufacturability and drug stability.
For the first time, we were able to see, on video, how the microneedles released the drug and swell as they hydrated. These videos are buried in the supplementary files for the paper, but I thought it worthy of sharing more widely here:
In this collaborative paper—our second with the Malaysian team led by Dr Choon Fu Goh—we examine some commercially available cosmetic products and ask what lessons we can learn from them to enhance pharmaceutical microneedle product translation and commercialisation.
We have known, for a long time, that the regulatory hurdles for pharmaceutical products are much greater than those for cosmetic products. Still, it’s interesting to see how cosmetic microneedle products have surged years (if not decades) ahead of their pharmaceutical counterparts, particularly in the Asian market. A low regulatory hurdle could spur innovation, but it could equally grow fad. How can one tell which it is? We examined a selection of commercially available cosmetic microneedle products to find out, and report our findings in this paper.
This has been an interesting paper to work on. I have admired Goh’s tenacity collecting microneedle patches from pharmacies on his various international trips across Asia for this study. Last year, I hosted him in Newcastle to conduct parts of the study, including some microscopy work and the optical coherence tomography (OCT) analysis on microneedle penetration in ex vivo pig skin. It’s rewarding to see those efforts pay off.
Citation: Chan HKY, Archbold L, Lau WM, Ng KW. Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies, Journal of Pharmaceutical Sciences, 2025:103837. https://doi.org/10.1016/j.xphs.2025.103837
We have a new paper out. This one is close to my heart because I personally spent many hands-on hours developing Otto.
Who’s Otto?
Otto is a Franz diffusion cell (FDC) autosampler robot. It replaces manual sampling and refilling of FDCs in a skin (and cornea, mucosal membrane, etc.) permeation experiment. Those who have worked with FDCs before would know how fiddly, time-consuming and labour-intensive that is. It’s a job most suited for a robot.
But Otto is about more than us trying to avoid menial labour. It’s about the quality of the science, too.
Let me rephrase that — it’s primarily about the quality of the science.
For a long time, we have noted many skin drug absorption studies that include unusually large sampling gaps of ≥16 hours, presumably because the researchers were unable to collect samples outside normal working hours. This sampling gap could allow the drug to accumulate in the FDC receptor chamber and, consequently, underestimate drug absorption due to sink condition being violated. We have faced similar logistical challenges ourselves as local rules prevent some researchers from working out of normal working hours. A FDC autosampler would solve these challenges, but we have not been able to afford any of the few commercial FDC automation systems available. When COVID-19 hit, and lab access was further restricted, we finally found the impetus and time to build the FDC autosampler we had always needed, for less than £500, and retrofitted it to our existing FDCs.
Thus, Otto was born.
Otto is a Franz diffusion cell (FDC) autosampler robot, adapted from the Creality Ender 3 Pro 3D printer. This picture depicts an automated skin permeation experiment using FDCs, in which Otto handled FDC sampling and refilling fully unattended. See the full paper for details on the number labels. Image reproduced under the CC BY 4.0 licence.
We have spent the last 2 years validating Otto’s performance. In this paper, we demonstrate that the sampling gap indeed led to violation of sink condition and underestimation of drug absorption. We further show that Otto improved data quality by avoiding the sampling gap. We have benchmarked Otto’s precision and accuracy against a trained researcher. We are pleased to report that it outperforms the researcher on both counts.
Otto is better than the commercial offerings in many ways. It is built on open-source technologies, using inexpensive consumables and 3D-printed custom parts, and is therefore fully customisable. It has a small footprint of just 50 cm × 46 cm. It can be retrofitted to generic FDCs and can collect up to 100 samples per experiment, fully unattended. The samples are collected directly into high-performance liquid chromatography (HPLC) autosampler vials, so it integrates seamlessly with downstream analysis without any further liquid handling, nor modification to the FDCs or analytical equipment.
Logistical, human resource and financial constraints continue to grip many research organisations long after COVID-19 restrictions have ended. Otto should prove itself a valuable asset in many research labs seeking to retrofit an automation solution to their existing FDCs.
The build instructions for Otto are too extensive to include in this paper, so we will be publishing them separately.
We have been working with Professor Katarina Novakovic‘s team for several years now to develop long-acting microneedle patch formulations based on our ULTRA technology. ULTRA stands for Ultra-long and Tunable Release of Actives. It is a polymeric composite material that confers exceptional sustained release properties.
Our work in this area is yet unpublished, but it has already attracted the attention of RTS (Radio Television of Serbia), which featured the ULTRA microneedle technology in a segment of the documentary series, A Guide to the Future (Vodič kroz budućnost). The full-length documentary is available on YouTube and is mostly in Serbian (Wing and I speak about the ULTRA microneedle technology in English). The segment about our ULTRA microneedle technology starts around the 17-minute mark.
Thanks to RTS and their crew for their invaluable time and efforts in creating this fantastic coverage.
One of the challenges in developing microneedle devices to capture disease biomarkers from the skin is the lack of suitable skin specimens in which to test the devices. Donor skin specimens that carry the specific target diseases simply do not come by easily.
We took a grounds-up approach by growing melanoma skin cancer cells in a three-dimensional (3D) culture, supported structurally by a biocompatible polymer scaffold. This allowed us to simulate not only the biological microenvironment around the cells, but also the three-dimensional structure of the skin for microneedle insertion. Importantly, it was a simple and inexpensive, yet versatile, laboratory model to set up.
In pioneering the 3D cell culture model for evaluating microneedle devices against a skin cancer biomarker, we also demonstrated – for the first time – successful capture of S100B (a biomarker for melanoma skin cancer) in situ using our immunodiagnostic microneedle device.
Stella Totti, formerly a PhD student and now a postdoctoral researcher in Eirini’s research group, is the first author. I am especially pleased that hard work has paid off for Lorraine Dale, a former MSc student of mine, who contributed greatly to this work and is a co-author on this paper.
We are now accepting applications for a funded PhD studentship in rapid disease diagnosis.
If you have read about our microneedle technology, and think that it is an area of research you would like to engage in and gain a PhD in the process, then please see the link below for eligibility and how to apply:
We have developed a microneedle array biosensor that can detect skin burns. To make the biosensor, we devised a nanocomposite material from carbon nanotubes and a biocompatible polymer, poly(lactic acid). We then shaped the microneedle array from the nanocomposite material. The microneedles that formed were about 870 μm long, 250 μm wide, and electroactive. This meant that the microneedle array could be inserted into the skin to detect certain analytes by electrochemistry. We verified this by using the microneedle array to detect vitamin C in solution. Interestingly, when we tested the microneedle array biosensor on skin burns and normal (non-burnt) skin, the skin specimens showed different electrochemical responses. This gives us the technological basis for a minimally invasive biosensing approach to detecting skin burns.
There are currently a couple of PhD studentships available within the pharmaceutics team at the School of Pharmacy, Newcastle University. Please click through the following links to find out more: