Periodic Reporting for period 1 - AutoDropProd (Development of a commercially-viable system for the automatic generation of high-throughput well defined single and double microdroplets) Período documentado: 2018-09-01 hasta 2020-08-31 Resumen del contexto y de los objetivos generales del proyecto Emulsions of microdroplets have been used in a wide range of applications especially in pharmaceutical and biosciences, cosmetics and food industries. However, most of the emulsions used consist of varying size (polydisperse) droplets. Polydispersity is particularly problematic in the pharmaceutical industry, where irregular drug quantities encapsulated in polydisperse drug-loaded droplets and particles can cause an initial burst of drug release in vivo, which can lead to undesirable cytotoxic effects. On the other hand, monodisperse emulsions can be produced, manipulated and analyzed using microfluidics. This is achieved by producing emulsions in micrometer sized channels in a droplet-by-droplet manner at kHz rates. Although this method produces droplets with size variations of less than 5%, for the pharmaceutical industry higher droplet size uniformity level is needed to achieve better control of drug encapsulation and release. Additionally, microfluidic approach at its current state, which is based on manual or semi manual droplet production, is not suitable for industrial applications, where high amounts of emulsion with the non-stop protocols are needed. To achieve this, physical parameters of droplets such as size, frequency and monodispersity has to be detected, monitored and regulated very rapidly for the long periods of time without human interaction.The most widely applied method to monitor physical parameters of the droplets such as droplet size and frequency, is the manual measurement. However, it does not advance us to automatization. Other existing methods are based on optical, electrical or even Artificial Intelligence (AI) droplet recognition. However, the low throughput or increased complexity of the systems, is not viable option for industrial applications. Thus, in this project it was designed and built a fully automatic, high throughput, real time droplet detection system which can produce monodisperse droplets and control their size for very long periods of time using a fast response pressure pump. This system solves two major problems concerning microdroplet emulsions – it ensures the conformity of droplet size and produces the emulsions at industrial levels without human intervention, making it the best option for scientific environment as well as for the industrial application. Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha During the time of the project a lot of work has been performed to achieve the goals of the project – starting from the market research for the new product all the way to device preparation and the market launch for beta testers. The market research showed that most people working with the droplets check their physical parameters manually and if there is some automatization it is minimal or very complicated and non-user-friendly, limiting its applicability. Additionally, there are just a few players in the market, but their solutions are just partial and lacks full problem-solving approach.Having in mind the results of the market research, it was designed and built a high throughput, automatic system to detect, measure and regulate the size of the droplets in microfluidic chip by integrating and synchronizing the strongest parts of several existing systems. It was combined fast optical detection of the droplets together with an automatic calibration based on AI image recognition and a fast feedback loop centered on quick response pressure pump to monitor and produce very uniform size droplets for long periods of time. The system can work with up to 10 kHz of droplet production rates as it is not limited by the processing power of the computer or data transfer speeds. Moreover, this approach does not depend on high speed cameras to photograph the droplets, lowering the cost of the system. The special design of the sample holder allows the use of almost any microfluidic chip making the system more versatile. The work was disseminated in a workshops, summer schools, two international conferences and by participating in open webinar where it was presented in an oral form to wide audience and recorded. The video of the presentation is open to everyone and it can be found on YouTube platform (https://www.youtube.com/watch?v=xXJ8K1DnVqc&ab_channel=Elveflow). Also, one scientific article was submitted to the international scientific journal as well as several white papers related to the subject have been written, which can be found on the www.elveflow.com webpage. Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha) The system created is fully automatized and does not need any user interference once the initial droplet parameters have been introduced, allowing 24/7 droplet production. This enables the wide-scale application of the microfluidics in the industry, where high throughput for long periods of time, without human interaction is very important. Finally, the systems capability to detect droplets and bubbles makes it very versatile and of potentially of universal implementation.The commercialization of above-described system will benefit greatly both scientific laboratories (in the fields of pharmacy, chemistry, biology, genetics, etc.), as well as the industries (food, pharmaceutical, cosmetics, chemicals). Firstly, the employment of monodispersed droplets for the experiments will improve dramatically the accuracy of the results. In addition, using monodispersed droplets as a “venue” for the experiments would help to cut the costs dramatically, especially in cases where expensive reagents and chemicals are used. Moreover, the new system will allow to minimize the usage of additives, such as emulsifiers, stabilizers and preservatives as finalized emulsions have longer shelf life. For the industries, the employment of automatic droplet regulation system will give an access to unlimited amounts of monodispersed emulsions, allow to simplify the procedures and to minimize manpower needed, leading to decrease in costs and increase in accuracy. One of the first beneficiaries of the droplet detection and regulation system could be the pharmaceutical industry that could use the system for drug encapsulation. We believe that in medium term (5-10 years) the new medicaments will be produced using microfluidics, that would enable to reduce the costs and have higher value products. fig4.jpg fig3.jpg remigijus-bella.jpg
