Periodic Reporting for period 4 - Droplet Microarray (Miniaturized System for Screening of Primary Cells based on Droplet Microarray)
Período documentado: 2023-01-01 hasta 2023-12-31
Current biological or cell screening systems are mainly based on microtitre plates. However, in personalised medicine, it is not possible to perform a large number of therapeutic tests on primary patient cells (e.g. biopsies) due to the high consumption of cells and reagents in microtitre plates. In preclinical drug research, the availability of rare primary cell types limits the potential for innovation as researchers have limited access to screening models relevant to human physiology. Making these rare cell types available for basic research, drug discovery, replacement of animal testing and personalised medicine will have a significant impact on society by enabling the development of novel drug therapies and diagnostics.
Further miniaturisation of current assays would inevitably enable the widespread use of rare cell types while reducing costs, increasing throughput and improving the biological relevance of screening results. DMA enables researchers and clinicians to perform meaningful experiments with primary cells and circulating tumour cells - alternative technologies hardly work at low cell numbers.
Aquarray has started this project to bring Droplet Microarray (DMA) technology to the market and develop a first version of an automated screening system. The Integrated Screening System (ISS) enables new therapeutic responses to cancer by using tumour cells from patients or other primary cells for diagnostics and therapy selection. With our miniaturisation approach, this type of testing becomes more affordable and also enables new approaches for high-throughput screening with cell-based assays in research and development.
In addition, Aquarray is actively developing partnerships with various technology providers for mass spectrometry, high-content microscopy and other applications to make its technology available to customers outside the cell-based screening and personalised medicine markets.
Further miniaturisation of current assays would inevitably enable the widespread use of rare cell types while reducing costs, increasing throughput and improving the biological relevance of screening results. DMA enables researchers and clinicians to perform meaningful experiments with primary cells and circulating tumour cells - alternative technologies hardly work at low cell numbers.
Aquarray has started this project to bring Droplet Microarray (DMA) technology to the market and develop a first version of an automated screening system. The Integrated Screening System (ISS) enables new therapeutic responses to cancer by using tumour cells from patients or other primary cells for diagnostics and therapy selection. With our miniaturisation approach, this type of testing becomes more affordable and also enables new approaches for high-throughput screening with cell-based assays in research and development.
In addition, Aquarray is actively developing partnerships with various technology providers for mass spectrometry, high-content microscopy and other applications to make its technology available to customers outside the cell-based screening and personalised medicine markets.
The project had a major impact on Aquarray and its development in many ways. Thanks to the support and co-funding of the project, Aquarray was able to build a strong brand name associated with the DMA's unique capability for biochemical and biological experiments as well as for screening compounds with a small number of primary cells. By participating in trade shows and exhibitions, communicating with customers via social media, videos, press releases and other communication channels, and continuously improving the website, Aquarray has steadily increased its visibility among customers, partners and collaborators. The implementation of various dissemination activities has led to increased visibility, which is reflected in the number of visitors to our website, LinkedIn followers and subscribers to our YouTube channel.
However, the acceptance of new technologies is slow and requires staying power, especially when it comes to the transition from pure research applications to use in personalised medicine, where regulatory hurdles must be overcome in addition to general acceptance of the technology.
In recent years, new laboratory technologies and equipment have been continuously developed and introduced. Aquarray will benefit from these developments, e.g. devices for replication of DMAs by sandwiching or devices for extraction of liquid from the spots for washing or sampling, for which prototypes are being developed or first commercial devices are already available. These developments will significantly expand the application possibilities and customer base for DMA technology, and Aquarray is actively participating in these developments and collaborating with institutes and companies that are driving these developments forward. Establishing the automated Integrated Screening System (ISS) as a product is a task that has a time horizon well beyond the funding period and will be continued with Aquarray’s own resources. Market research carried out as part of this project has shown that the availability of DMAs with pre-printed compound libraries is a prerequisite for the full utilisation of the ISS and for attracting customers who have limited access to devices for printing compounds onto the DMA.
An important achievement during the project was the ISO 9001 certification, which helped to increase the company's overall credibility and led to the optimisation of various processes. The reorganisation of processes according to ISO 9001 requirements led to improved documentation and interaction with customers, optimisation of various processes, introduction of frequent and structured review of strategic risks and search for potential errors, and helped Aquarray achieve greater efficiency in all company activities. It also led to further improvements in the production process. Tools and processes were optimised to increase pattern accuracy, which improves product quality and increases customer satisfaction, and to improve the scalability of the production process, enabling higher throughput. As a result of these improvements, the amount of scrap produced has also been significantly reduced, improving production efficiency and costs. Another goal was to reduce the time required for quality control after production of the DMA-Slides while ensuring functional and reliable measurements. The quality control of the DMAs was optimised by comparing different techniques to visualise the hydrophilic spots on a hydrophobic background. After optimising the protocol, quality control can be performed manually by adding steam instead of water to each spot. This leads to a time saving of at least 50 %.
The DMA-Slides in their current form offer many advantages for the user. However, for some customers, especially where automation is required, the slide format is a disadvantage. They are not easy to adapt to laboratory equipment and the manual handling is not user-friendly. An overriding goal was to develop a DMA-Cartridge in ANSI microplate format. This format is used in common laboratory automation systems and it is therefore very important to adapt the DMA to this format. Therefore, the design of the DMA-Cartridge was iteratively optimised using 3D printing technology. Based on the final design, the DMA-Cartridges were manufactured, tested and are currently being launched on the market.
However, the acceptance of new technologies is slow and requires staying power, especially when it comes to the transition from pure research applications to use in personalised medicine, where regulatory hurdles must be overcome in addition to general acceptance of the technology.
In recent years, new laboratory technologies and equipment have been continuously developed and introduced. Aquarray will benefit from these developments, e.g. devices for replication of DMAs by sandwiching or devices for extraction of liquid from the spots for washing or sampling, for which prototypes are being developed or first commercial devices are already available. These developments will significantly expand the application possibilities and customer base for DMA technology, and Aquarray is actively participating in these developments and collaborating with institutes and companies that are driving these developments forward. Establishing the automated Integrated Screening System (ISS) as a product is a task that has a time horizon well beyond the funding period and will be continued with Aquarray’s own resources. Market research carried out as part of this project has shown that the availability of DMAs with pre-printed compound libraries is a prerequisite for the full utilisation of the ISS and for attracting customers who have limited access to devices for printing compounds onto the DMA.
An important achievement during the project was the ISO 9001 certification, which helped to increase the company's overall credibility and led to the optimisation of various processes. The reorganisation of processes according to ISO 9001 requirements led to improved documentation and interaction with customers, optimisation of various processes, introduction of frequent and structured review of strategic risks and search for potential errors, and helped Aquarray achieve greater efficiency in all company activities. It also led to further improvements in the production process. Tools and processes were optimised to increase pattern accuracy, which improves product quality and increases customer satisfaction, and to improve the scalability of the production process, enabling higher throughput. As a result of these improvements, the amount of scrap produced has also been significantly reduced, improving production efficiency and costs. Another goal was to reduce the time required for quality control after production of the DMA-Slides while ensuring functional and reliable measurements. The quality control of the DMAs was optimised by comparing different techniques to visualise the hydrophilic spots on a hydrophobic background. After optimising the protocol, quality control can be performed manually by adding steam instead of water to each spot. This leads to a time saving of at least 50 %.
The DMA-Slides in their current form offer many advantages for the user. However, for some customers, especially where automation is required, the slide format is a disadvantage. They are not easy to adapt to laboratory equipment and the manual handling is not user-friendly. An overriding goal was to develop a DMA-Cartridge in ANSI microplate format. This format is used in common laboratory automation systems and it is therefore very important to adapt the DMA to this format. Therefore, the design of the DMA-Cartridge was iteratively optimised using 3D printing technology. Based on the final design, the DMA-Cartridges were manufactured, tested and are currently being launched on the market.
The results of this project will have a major impact on the screening market as it will enable the screening of very expensive and very limited biological materials. In this way, it has the potential to change the industrial and academic research and development landscape. As the technology enables a high degree of parallelisation and miniaturisation, it will enable new developments outside the life sciences, e.g. in combinatorial screening and related fields.
It is expected that the ISS will be recognised as a cost-effective alternative to expensive automation devices in research and personalised medicine. The acceptance of DMA technology and ISS by users and the wider scientific community will help to open up new avenues for personalised medicine and the screening of new bioactive molecules. It will also enable the screening of expensive compounds or compounds with limited availability and scarce cells, which was not previously possible. We expect to further advance the integration of on-chip chemical synthesis, biological assays and multiple readout capabilities, with the possibility of further automation and device integration.
It is expected that the ISS will be recognised as a cost-effective alternative to expensive automation devices in research and personalised medicine. The acceptance of DMA technology and ISS by users and the wider scientific community will help to open up new avenues for personalised medicine and the screening of new bioactive molecules. It will also enable the screening of expensive compounds or compounds with limited availability and scarce cells, which was not previously possible. We expect to further advance the integration of on-chip chemical synthesis, biological assays and multiple readout capabilities, with the possibility of further automation and device integration.