Periodic Reporting for period 1 - ARTS (Precision tissue biobanking made easy)
Période du rapport: 2023-01-01 au 2024-12-31
To treat and understand the underlying mechanisms in various human diseases including cancers, the investigation of high-quality human and animal tissues is crucial. Large-scale biobanks are therefore essential to meet the world-wide demand for high-quality tissues to answer urgent research questions. Targeted tissue types such as tumors, stroma cells or epithelial cells are usually not visible to the eye hence, in my ERC project, we developed a technology enabling us to collected targeted tissue sub-samples based on clinical pathology readings. Our solution was developed for high-quality fresh frozen prostate tissue for metabolomics, transcriptomics and genomics analysis. During this proof of concept project, we explored the possibility to develop our technology into a generalised tissue harvesting and sub-sampling procedure. Our aim was to obtain a semi- or fully automated tissue harvesting protocol by an Augmented Reality enhanced and an automated Tissue Sampler (ARTS), a technology that was aimed to be cost-effective, simple to operate, and allow maximal tissue utilization.
According to the first work package including design and fabrication, we have fulfilled the 4 milestones of the application; optimize sample detection and process monitoring by improving the existing camera setup, automate sample and drill positioning system, implement an automated sub-sample collection system and implement a closed system concept to allow control of environmental parameters. The project has undergone three stages of development. In the first stage, a team of students together with NTNU’s prototype laboratory TrollLABS proposed Computer Numerical Control (CNC) milling for cutting out samples. In the second stage, they tested the CNC milling, explored various non-invasive sample gripping solutions to secure slices during milling, and implemented a closed cooling solution. In the third and final stage, a new and improved tissue sampler was designed, built and tested to be fully capable of extracting tissue samples for cellular research. It was able to extract samples from anywhere on frozen slices of diverse tissue types, including real human prostate, with precision and no limitations to sample shape or size. It was simultaneously able to keep the slices below -10°C, thus preserving the biological integrity of the tissues. Several components, like the semi-automatic collection system and a spring-based clamping mechanism, were developed to illustrate the potential of automation. The testing also confirmed applicability to a broad variety of tissue types and an improved user-friendliness. This work is currently summed up in the form of a HardwareX article for open access publication with a planned submission in autumn of 2025.
To advance interface in work package 2, we hired a company, involving a product designer, mechanical engineer, and a cybernetic engineer. The initiative was structured into two phases: an insight phase to explore the product's potential and a subsequent phase focused on refining the existing prototype. This resulted in a 5-axis milling machine designed for a controlled environment. The second phase focused on improving the existing prototype with an emphasis on usability and quality control. Key enhancements were made to address temperature regulation and operational safety. Improvements that were implemented was 1) a new end mill holder for safer and more efficient end mill changes, reducing operational time and minimizing the risk of injury 2) a redesigned sample clamping system utilizing anodized aluminum to enhance stability during milling processes 3) an automated sample collection using a 2-axis CNC-operated robot for automated sample collection, designed to fit standard sample boxes, thereby streamlining workflow and reducing manual intervention. These enhancements improved functionality and opened new opportunities for medical research. Continued testing and validation will be crucial to confirm benefits. Ongoing engagement with users and stakeholders was recommended to ensure the system meets their needs and supports operational efficiency. In Work Package 3, the Technology Transfer Office (TTO) conducted IP and strategy mapping, considered IPR issues, engaged with industry, gained market insights, and explored business models. Early in the project, it was found that broad patent protection for the new prostatectomy specimen analysis method was difficult due to the invention’s early stage and existing patents from major industry players. As development progressed, technological changes required ongoing IP reviews. The resulting strategy focused on identifying distinct, potentially patentable elements. Throughout the ARTS project, TTO continued assessing IP, culminating in a draft IP asset list by 2024. The latest review identified both patentable and non-patentable but unique assets. No current patentable assets have been found, though other protection routes are being considered. These assets may hold commercial value if industry partners are interested in licensing or acquiring them. However, commercialization may be hindered by the use of patient-specific data and images. The IP landscape includes patents from Roche, Becton, Dickinson and Company, and Philips, covering biopsy and tissue collection technologies.
Market insight involved industry interviews of biobanks and core facilities where TTO identified 52 actors, the most relevant actors were contacted; 6 showed no interest,10 were interviewed, and 7 were engaged in email correspondence. The results revealed that the identified customer group is small, with limited needs, as not all biobanks had relevant tissue and funding. The growth rate of biobanking did not support huge investments. In addition, significant modifications would be necessary for implementation due to the absence of both national and international standards for tissue sample collection. We experienced unforeseen delays during the latest prototype development, that prevented us from collecting feedback from interested parties before the end of this PoC project. Thus, there might be more information collected from these or other relevant actor groups.
Throughout the project, innovation readiness level (IRL) assessments were conducted several times for structure and support for idea owners and NTNU TTO in the development of an early-stage idea to an innovation on the market. The business plans discussed have highlighted challenges that biobanks do not have business plans but are publicly funded and they are bound to strict regulations. The market interviews indicated that implementation required extensive changes due to the lack of national and international standards for tissue sample collection. Several biobanks have their own protocols or set-up. This might however change in the future and then and possible commercial opportunities might appear.
To advance interface in work package 2, we hired a company, involving a product designer, mechanical engineer, and a cybernetic engineer. The initiative was structured into two phases: an insight phase to explore the product's potential and a subsequent phase focused on refining the existing prototype. This resulted in a 5-axis milling machine designed for a controlled environment. The second phase focused on improving the existing prototype with an emphasis on usability and quality control. Key enhancements were made to address temperature regulation and operational safety. Improvements that were implemented was 1) a new end mill holder for safer and more efficient end mill changes, reducing operational time and minimizing the risk of injury 2) a redesigned sample clamping system utilizing anodized aluminum to enhance stability during milling processes 3) an automated sample collection using a 2-axis CNC-operated robot for automated sample collection, designed to fit standard sample boxes, thereby streamlining workflow and reducing manual intervention. These enhancements improved functionality and opened new opportunities for medical research. Continued testing and validation will be crucial to confirm benefits. Ongoing engagement with users and stakeholders was recommended to ensure the system meets their needs and supports operational efficiency. In Work Package 3, the Technology Transfer Office (TTO) conducted IP and strategy mapping, considered IPR issues, engaged with industry, gained market insights, and explored business models. Early in the project, it was found that broad patent protection for the new prostatectomy specimen analysis method was difficult due to the invention’s early stage and existing patents from major industry players. As development progressed, technological changes required ongoing IP reviews. The resulting strategy focused on identifying distinct, potentially patentable elements. Throughout the ARTS project, TTO continued assessing IP, culminating in a draft IP asset list by 2024. The latest review identified both patentable and non-patentable but unique assets. No current patentable assets have been found, though other protection routes are being considered. These assets may hold commercial value if industry partners are interested in licensing or acquiring them. However, commercialization may be hindered by the use of patient-specific data and images. The IP landscape includes patents from Roche, Becton, Dickinson and Company, and Philips, covering biopsy and tissue collection technologies.
Market insight involved industry interviews of biobanks and core facilities where TTO identified 52 actors, the most relevant actors were contacted; 6 showed no interest,10 were interviewed, and 7 were engaged in email correspondence. The results revealed that the identified customer group is small, with limited needs, as not all biobanks had relevant tissue and funding. The growth rate of biobanking did not support huge investments. In addition, significant modifications would be necessary for implementation due to the absence of both national and international standards for tissue sample collection. We experienced unforeseen delays during the latest prototype development, that prevented us from collecting feedback from interested parties before the end of this PoC project. Thus, there might be more information collected from these or other relevant actor groups.
Throughout the project, innovation readiness level (IRL) assessments were conducted several times for structure and support for idea owners and NTNU TTO in the development of an early-stage idea to an innovation on the market. The business plans discussed have highlighted challenges that biobanks do not have business plans but are publicly funded and they are bound to strict regulations. The market interviews indicated that implementation required extensive changes due to the lack of national and international standards for tissue sample collection. Several biobanks have their own protocols or set-up. This might however change in the future and then and possible commercial opportunities might appear.
To conclude, we have successfully developed a proof of concept, a ready-to-use prototype of a medical device for biobanks and researchers to perform tissue extraction. We plan to create a short video to explain the device further, which can be used to further engage companies and other stakeholders. Based on findings from our market research, we decided to publish design and results of the second iteration of the ARTS prototype in form of an open access article to increase the dissemination of our technology in the public research sector.