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Large area interferometric imager for highly sensitive inspection of materials

Periodic Reporting for period 1 - LIM (Large area interferometric imager for highly sensitive inspection of materials)

Reporting period: 2021-10-01 to 2022-09-30

The accurate and rapid inspection of transparent materials and substrates is of utmost importance for several high-tech areas in the material and life science industries. In particular, life science industry strongly relies on the imaging and analysis of cell cultures which offer intrinsically low contrast and are thus very challenging to inspect.
Optical microscopes can detect objects by means of several physical processes, such as light emission, scattering, absorption and reflection. However, for highly transparent samples, such as cells, these mechanisms are often too weak for obtaining high contrast images. In cell imaging, some of the most common and effective solutions to this problem involve the use of fluorescent labels, which can be linked to antibodies that target specific parts of the cell. Fluorescent techniques allow to obtain high contrast images but can easily compromise cell’s health, leading to wrong results for in-vitro toxicity and drug development studies. In this context, different label-free photonic imaging techniques have emerged to address these limitations.
In this project, innovative proprietary phase imaging optoelectronic prototypes have been developed and validated with different types of optical materials and cells. Compared to existing market solutions, the advanced label-free prototypes offer ultra-sensitive and stable quantitative phase imaging by means of mass-scalable and cost-effective optoelectronic designs that can be developed into either full-imagers or add-on systems.
The accurate imaging and study of cells without compromising their health and behaviour is of fundamental importance for several life-science industries. For instance, life-cell imaging, toxicology and regenerative medicine are three sectors that strongly rely on the characterization and monitoring of cell’s response to different conditions. In these fields, the development of a highly sensitive and compatible label-free imaging platform that offers new or complementary learnings not accessible today could enable new learnings and discoveries.
The commercialization of such innovative phase imaging devices could also have a significant impact for society in material science industries with applications such as in-line metrology, surface inspection or automated optical inspection.
The overall goal of the project was to validate the patented imaging device prototypes within different industrial environments and evaluate related business cases and market potentials. The three key objectives of the project were to i) analyse customer-relevant samples and evaluate their demand, ii) adapt and integrate the LIM prototypes into industrial environments and to iii) define a commercialization process with strategy of technology transfer.
During the project, key features and technical specifications of the technology have been identified and a process for their verification has been developed, adopting industry standards. Four different sets of technical requirements have been addressed by analysing different end-customer needs and application cases. Additionally, multiple prototypes have been developed to address the different needs and applications that the technology could serve. This include the lens-free LIM with a large field of view, compact and robust; the standalone LIM that includes imaging lenses and accepts a wide variety of commercial magnification objectives to allow high spatial resolution; and the add-on LIM that fits into standard optical microscope and is the most compatible and affordable solution.
Some of the prototypes were developed with several hardware and software improvements implemented based on initial market feedback have been tested with different end-customers and samples, including a long-period leasing and testing at an industrial end-customer’s premises. In this context, some of the improvements included new software to store data and overcome phase-wrapping difficulties as well as new algorithms to reduce phase imaging defects observed during the testing periods.
With the goal of commercially exploiting the results, a detailed market and competitor analysis of the different technologies and companies in the fields relevant for the technology have been performed, highlighting the potential market opportunities and key competitive advantages. In particular, the global microscopy market was analysed in terms of size, key players, final applications, regional segmentation and global trends. In terms of the competitor analysis, multiple phase-imaging solution providers have been identified and their solutions have been technically analysed to identify key competitive advantages of the proposed solution.
A systematic intellectual property position review and landscape assessment has also been performed in preparation of a new invention disclosure. In particular, this review has required the analysis of up to 40 potentially relevant documents including peer-reviewed scientific articles and patents. On top of that, the main building blocks of the proposed business model to commercialize the manufacture and distribution of the phase imaging devices has been completed.
In terms of dissemination, the project has been presented to multiple end-users across different research centres, leading microscopy corporations and small or medium enterprises. We have been in contact with more than 70 end-customer during 2021, with the most relevant interactions taking place since October 2021. The team has engaged and participated in two international industry-focused conferences and the innovative and potential impact of the project has been recognized with a first prize in one of the conferences. Additionally, the project has been disseminated across different webpage publications, social networks and in a podcast.
During this project the LIM technology has been developed to go beyond the state of the art and the requirements communicated by the customer interactions. On the one side the sensitivity of the device has remained as high as to identify the single nanometric features. On the other side, the acquisition speeds and compatibility of the tool have dramatically increased, resulting in a technology that will enable new industrial applications.
In terms of economic and social impact, all the envisioned applications for the LIM technology can be related to the microscopy market. This market presents huge niche opportunities as end-users require new technologies with improved capacities therefore pushing key microscope players to invest in new devices, either through their R&D and partnerships, or through licensing agreements.
The market and competitor analysis performed throughout the project have revealed that the LIM technology has the potential to bring several competitive advantages and unique selling proposition to the market. Initial projection estimations based on the business model assumptions performed indicate that with an initial investment of 1-1.5 M€ the spin-off could reach an estimated revenue above 30 M€ across the different revenue channels in five years to place up to 50.000 LIM devices in public and private research laboratories across Europe and United States.
Application examples of the LIM technology
Comparison of the traditional and LIM imaging solutions for neuron samples
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