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TESTING


and used for testing in a miniaturized flow- through setup, allowing topical and systemic applications (Figure 1b). Microfluidic channels in the REVex chip can mimic dynamic blood flow perfusion beneath the skin tissue, adding a fourth dimension to skin testing. This recreates in-vivo-like conditions, as the continuous flow of the receptor solution can be fine-tuned by the user, for a closer mimicking of the human body microenvironment. ReleGO is a fully-automated skin-on-


chip fraction collector for safety, efficacy and permeation studies that enables more reliable and faster data on new drugs, cosmetics and chemical ingredients (Figure 2). The system can integrate up to 4 REVex devices, allowing simultaneous testing of 12 skin tissues per one experiment. A touch screen with an intuitive user


interface allows adjusting different testing conditions such as flow rate, temperature and time collection intervals, ultimately enabling effortless long-term experiments. When skin simulants are loaded in the


REVex chips, a continuous flow of receptor solution is pumped beneath them: the collection of the outflow is then performed automatically into the wells of 96-well plates. The molecule of interest can be analyzed over time directly using a plate reader (Figure 3) or other sensitive analytical techniques (eg. LC- MS/MS, ICP/MS).


Overcoming the limitations of current state-of-art testing REVIVO BioSystems microfluidic technology increases throughput as manual operations are minimized and many ReleGO systems can be easily run in parallel. More test samples can be screened in a shorter period of time, as opposed to incumbent methods (Table 2), and the end-to-end path to the market can be


TABLE 2: DIFFUSION CELL VERSUS REVEX CHIP * PRECISION MEASURED DURING PERMEATION EXPERIMENT ON SYNTHETIC MEMBRANES TO VALIDATE THE DESIGN OF THE MICROFLUIDIC DEVICE AGAINST FRANZ CELLS


Franz diffusion cell


Geometric* precision (CV%) l


Caffeine


l Salicylic Acid l Testosterone


Cleaning after use Skins per device


3-8% 3-8% 5-10%


Required


(>50$ per cycle of autoclave) 1


more productive for ingredients and finished products. Testing protocols, including recovery for mass balance, can be fully automated, thus saving hours of manual work. The diameter of each skin tissue disc loaded


on the REVex device is 8 mm. Therefore, with the same skin area needed for a diffusion cell, four to ten tests can be conducted using the REVex chip. This allows savings on biomaterials as it requires much smaller skin samples. The microfluidic design guarantees laminar


flow in the lower compartment, preventing undesired accumulation and the occurrence of unstirred water layers. At the same time, the user can choose the most suitable flow rate for the receptor solutions, so that the penetrated compound does not get too diluted or too concentrated. Thanks to the dynamic conditions, the viability of real human tissue explants can also be extended for long term studies.


Conclusion With continuous efforts being put into the development of ReleGO and in microfluidic techniques, users can look forward to more sophisticated systems for studying skin metabolism, cell-cell interactions, and the


REVex chip


1-2% 1-2% 5-8%


No (disposable) 3


screening of cosmetics ingredients and therapeutic drugs for many years to come. Revivo Biosystems will continue to drive next-generation skin-on-chip platforms that will bring us closer and closer to real-time testing and to mimic the natural complexity of living human skin, giving us a promising reason to choose such in vitro and ex vivo testing platforms over animal tests. The REVex chip and ReleGO platform


can be used not only for permeation but also for replacing Ussing chambers for gut related studies, for safety and efficacy studies on skin and oral mucosa equivalents, with the advantage to have more granular, time- sensitive analysis of soluble factors that those tissues may release. The combination with multiplexed cytokines and growth factors assays, for example, may open avenues for more insightful data and studies that were not previously imagined.


127


PC


Reference 1. Alberti M, Dancik Y, Sriram G, Wu B, Teo YL, Feng Z., Bigliardi-Qi M, Wu RG, Wang ZP, Bigliardi P. Multi-chamber microfluidic platform for high precision skin permeation testing. Lab Chip 2017;17:1625-34.


Figure 4: Flowchart for setting up a study with the microfluidic approach www.personalcaremagazine.com April 2023 PERSONAL CARE


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