Category: News

Keep abreast with latest developments in our research team.

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Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies

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

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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.

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ULTRA microneedle patch technology featured on Serbian national TV

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.

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Rach successfully defends PhD thesis

Rach Dixon (soon to be Dr Dixon officially) successfully defended her PhD thesis. The title of her thesis was Development of a Minimally Invasive Microneedle Immunosensor to Detect Biomarkers in the Skin.

Congratulations, Rach!

Rach’s work has brought many firsts to our group, including a new microfabrication technique and a new signal detection platform. It’s been a pleasure working with her and we are utterly delighted for her success.

The examiners were Dr Al Edwards (University of Southampton) and Dr Neil Keegan (Newcastle University). The examination was chaired by Professor Sarah Slight. We thank them for conducting a smooth PhD examination. Thanks also to the administrative staff involved in organising it.

Here’s everyone beaming after the examination:

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Hot off the press: Elastin-derived peptide-based hydrogels as a potential drug delivery system

Keng has published a new paper out with Dr Othman Al Musaimi and co-workers. In this paper, we report the development of a self-assembling hydrogel formulation based on peptide sequences derived from elastin.

Elastin is a naturally occurring protein found in many connective tissues in the body, including the skin and blood vessels. These peptide sequences have been selected carefully to promote self-assembly of the hydrogels and confer the desired mechanical properties to the hydrogel. This hydrogel can be an interesting drug delivery system. The ability for the hydrogel to self-assemble at room temperature makes it easier to incorporate drugs into the hydrogel matrix. The mechanical properties will determine the rate at which the drugs can then be released from the hydrogel.

The paper is open access and free to read, so head over there now to read the full text for free.

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Hot off the press: Mathematical modelling of genipin-bovine serum albumin interaction using fluorescence intensity measurements

Hydrogels are a popular drug delivery vehicle. You can encapsulate drugs including large biological macromolecules like proteins in them, to be released in the body. Some hydrogels use chemical crosslinking to create the hydrogel matrix – with the drug in it. Can protein drugs encapsulated this way participate in those crosslinks? What if they do? How will that affect their subsequent release?

We started asking these questions when attempting to deliver protein drugs by encapsulating them in hydrogel-forming microneedle array patches. These were important questions, and now we have the answers.

In this paper, we address these questions using bovine serum albumin as a model drug, and a genipin-chitosan hydrogel as the drug delivery vehicle. Using a combination of empirical fluorometry data and mathematical modelling, we investigate the kinetics of the interactions of the protein drug and genipin (the crosslinker).

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Group photos and social

We probably should do this more as a group.

Don’t get me wrong, we do socialise daily, but we don’t document it the way we document our experiments meticulously. So, before people start to disappear for their summer breaks, Wing had the brilliant idea of a lab photo and a meal together.

It was a shame that we couldn’t get everyone in one photo, but people deserve to take their holidays when they want them! So, we gathered up the boffins on two separate occasions and collected photographic evidence of them in full PPE (personal protective equipment, for the uninitiated), thoroughly committed to their research and enjoying it. We then headed off for a meal and a afternoon chat filled with laughter, talking mostly about ‘safe hobbies’.

We really should do this more.

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Hot off the press: In vitro evaluation of microneedle strength: a comparison of test configurations and experimental insights

We test our microneedles a lot to examine how they fail. The most common technique we use to quantify the mechanical strength of the microneedles is by applying axial compression (crushing the microneedles from the tip towards the base) on a texture analyser, and pinpointing the minimum force that results in microneedle failure. We’re fortunate that our lab is well equipped to perform these tests. We get a live video feed of what’s happening to each microneedle as it’s being compressed. We can also playback the videos and analyse them synchronously with the force-displacement data. This technique has proved invaluable in making sure our microneedles perform as they should.

Hence, when Dr Choon Fu Goh invited me (Keng) to contribute to this paper on the mechanical testing of microneedle strength, I jumped at the opportunity. This is our first paper together and I really enjoyed working on this. I hope the microneedle community finds it useful.

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Welcome Bohan!

Bohan Zhou, who spent several weeks as a research intern in our lab last year, has rejoined us to study a PhD in microneedle biosensing. We have a very interesting project lined up. Welcome back, Bohan!

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Grace passes PhD viva without corrections!

Many congratulations to Grace Young who has passed her PhD viva – without corrections, I might add. This is an incredible feat. Congratulations, Dr Young! This is very well deserved.

Thanks, Professor Brendan Gilmore and Dr Chien-yi Chang, for conducting the examination.

Grace was supervised by Dr Wing Man Lau, Professor Nick Jakubovics and myself. The title of her thesis is “Development of a novel antimicrobial and drug delivery strategy to combat biofilm”.

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Micromoulding microneedle array patches under vacuum, hands-free!

Our hands-free, ‘vac-and-fill’ micromoulding technique prevented air entrapment and bubble formation in viscous formulations when degassed under vacuum. Image from Smith E, et al. Int J Pharm 2024;650:123706. Licence: CC BY 4.0 Deed.

Our latest paper, Vac-and-fill: A micromoulding technique for fabricating microneedle arrays with vacuum-activated, hands-free mould-filling, has been published in the International Journal of Pharmaceutics. It’s open access, so head over there to read the full-text article for free!

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This paper reports the solution to a problem that took us several months to solve. We were trying to mould a microneedle array patch. There are basically two ways to do it: you fill the mould with the liquid formulation and either centrifuge it or degas it under vacuum. Both techniques are widely reported in the literature. They have been designed to force any air out of the microcavities in the mould, so that the formulation can enter them to form the microneedles. We didn’t have the right rotor to go with the centrifuge, so we opted for the vacuum degassing technique, fully expecting it to be a walk in the park. What a disappointment that turned out to be! We discovered that our formulation was too viscous to allow the air to escape. We ended up with a lot of air bubbles trapped in the liquid formulation.

We quickly realised that the vacuum degassing technique reported in the literature had used low polymer concentrations, which meant that their liquid formulations were not as viscous as ours. To micromould the microneedle array patch successfully from our viscous formulation, we had to remove the air first before filling the formulation into the mould. But how would one fill the mould under vacuum?

The answer: a modified syringe, a 3D-printed part, some painstaking calibration, and viola! The paper describes our solution in full, but here’s a peek of the contraption in action.

This is Emma’s first paper and our first together with Dr Katarina Novakovic‘s group. Congratulations, Emma, and thank you team for the hard work!