Periodic Reporting for period 1 - DISRUPT (On-chip tomographic microscopy: a paraDIgm Shift for RevolUtionizing lab-on-a-chiP bioimagingtechnology)
Reporting period: 2022-12-01 to 2023-11-30
The long-term vision of DISRPUT is to revolutionise the field of biomedical imaging by developing a radically new lab-a-on-chip technology: integrated tomographic microscopy. This unprecedented technique will be enabled by pushing forward the science of on-chip wireless photonics (OWP) and tomography, in combination with microfluidics and artificial intelligence (AI). The CMOS compatibility of this technology represents a paradigm shift, as it assures the realization of TPM microscopes that are dramatically cheaper, lighter, and smaller than current approaches. Moreover, the singular features of the proposed solution introduce key advantages in terms of resolution, sensitivity, throughput, parallelisation, and energy efficiency. To illustrate its potential, we will show that on-chip TPM can be used for cancer detection and the identification of infected cells. Our project encompasses a comprehensive and multifaceted design and testing process, focused on the development of an advanced photonic system for detailed biological analysis. A detailed analysis of the technical objectives together with their completion levels after this first year is provided in the next section.
In this section, we enumerate the comprehensive list of objectives for the entire project. Attached below these are tables in which we highlight the expected level of progress for these objectives, as well as the actual progress achieved in this year of work. For those objectives that have not yet commenced, we simply indicate that the tasks related to them have not yet begun.
O1. Design and experimental validation of a low-directivity NA (gain < 7 dB) to act as a cylindrical-wave emitter and of a high-directivity NA (gain > 20 dB) to act as the pixels of the visible scattered-field detector.
Expected level of completion at the end of RP1 60%
O1.1. Acquired the know-how necessary to extend the application of silicon nanoantennas and other structures to silicon nitride.
O1.2. Specify the requirements of the transmitting nanoantenna (cylindrical-wave emitter)
O1.3. Final design of the high directivity nanoantenna.
Real level of Completion 40%
O1.1. Completed.
O1.2. In progress.
O1.3. In progress.
O2. Design and test of a holographic detection module suitable for on-chip tomography based on interferometric junctions, including the grating couplers and the CCD detector.
Expected level of completion at the end of RP1 Design 50% Test 0%
O2.1. Definition of required building blocks.
O2.2. Define preliminary used system for measurements.
O2.3. Determine the discrete devices used for the setup.
O2.4. Define the demonstrator.
Real level of Completion Design 50% Test 0%
All objectives completed – for further information, see D2.1
O3. Design and test of the complete photonic subsystem based on the developments of O1 and O2.
Expected level of completion at the end of RP1 Design 30% Test 0%
O3.1. Fabrication of channel.
O3.2. Layout of the subsystem with the I/O devices and chip blueprint.
Real level of Completion Design 30% Test 0%
O3.1. Completed.
O3.2. Completed.
O4. Design and test of the microfluidic system to include the optical interface to the TPM and to carry out all fluidic operations, including the presentation of the cells in a sheath flow arrangement to the optical field for analysis.
Expected level of completion at the end of RP1 Design 30% Test 0%
O4.1. Concept of the microfluidic system
Real level of Completion Design 30% Test 0%
O4.1. Completed.
O5. On-chip integration of the systems developed in O3 and O4 to build the on-chip TPM microscope.
The tasks related to this Objective have not yet begun.
O6. Implementation of a diffraction tomography algorithm adapted to the tomographic microscope of O5.
Expected level of completion at the end of RP1 100%
O6.1. Linear detector.
O6.2. Circular detector.
O6.3. Synthetic aperture with moving source.
O6.4. Synthetic aperture for moving sample.
O6.5. Synthetic aperture for moving sample with circular detector.
Real level of Completion 70%
O6.1. Completed.
O6.2. Completed.
O6.3. Algorithm implemented – simulation error detected and working on it. (status: 80%)
O6.4. Algorithm developed and expected to work on O6.3 completion. (status: 80%)
O6.5. Initial hypothesis of system reduction from 3D to 2D. (status: 5%)
O7. Artificial intelligence. - We will employ classical statistical approaches and DL to distil and extract the relevant information from the RI images provided by the TPM, which will be crucial to manage such a large amount of data and will help during the LoC design and the training and validation of a reliable system. The developed AI algorithms will guarantee important predictive model features such as robustness, explainability, unbiased and trustworthiness.
The tasks related to this Objective have not yet begun.
O8. Laboratory demonstration of a device able to detect synthetic healthy cells and Urological Cancer (Uca) and Gynaecological Cancer (GCa) Tumour cells (TCs) based on the optimisation of the TPM microscope, the microfluidic system and DL algorithms of O4-O7.
The tasks related to this Objective have not yet begun.
O9. Laboratory demonstration of a device able to detect individual cells infected with viruses or bacteria in a heterogeneous population based on the results of O5-O7.
The tasks related to this Objective have not yet begun.
O1. Design and experimental validation of a low-directivity NA (gain < 7 dB) to act as a cylindrical-wave emitter and of a high-directivity NA (gain > 20 dB) to act as the pixels of the visible scattered-field detector.
Expected level of completion at the end of RP1 60%
O1.1. Acquired the know-how necessary to extend the application of silicon nanoantennas and other structures to silicon nitride.
O1.2. Specify the requirements of the transmitting nanoantenna (cylindrical-wave emitter)
O1.3. Final design of the high directivity nanoantenna.
Real level of Completion 40%
O1.1. Completed.
O1.2. In progress.
O1.3. In progress.
O2. Design and test of a holographic detection module suitable for on-chip tomography based on interferometric junctions, including the grating couplers and the CCD detector.
Expected level of completion at the end of RP1 Design 50% Test 0%
O2.1. Definition of required building blocks.
O2.2. Define preliminary used system for measurements.
O2.3. Determine the discrete devices used for the setup.
O2.4. Define the demonstrator.
Real level of Completion Design 50% Test 0%
All objectives completed – for further information, see D2.1
O3. Design and test of the complete photonic subsystem based on the developments of O1 and O2.
Expected level of completion at the end of RP1 Design 30% Test 0%
O3.1. Fabrication of channel.
O3.2. Layout of the subsystem with the I/O devices and chip blueprint.
Real level of Completion Design 30% Test 0%
O3.1. Completed.
O3.2. Completed.
O4. Design and test of the microfluidic system to include the optical interface to the TPM and to carry out all fluidic operations, including the presentation of the cells in a sheath flow arrangement to the optical field for analysis.
Expected level of completion at the end of RP1 Design 30% Test 0%
O4.1. Concept of the microfluidic system
Real level of Completion Design 30% Test 0%
O4.1. Completed.
O5. On-chip integration of the systems developed in O3 and O4 to build the on-chip TPM microscope.
The tasks related to this Objective have not yet begun.
O6. Implementation of a diffraction tomography algorithm adapted to the tomographic microscope of O5.
Expected level of completion at the end of RP1 100%
O6.1. Linear detector.
O6.2. Circular detector.
O6.3. Synthetic aperture with moving source.
O6.4. Synthetic aperture for moving sample.
O6.5. Synthetic aperture for moving sample with circular detector.
Real level of Completion 70%
O6.1. Completed.
O6.2. Completed.
O6.3. Algorithm implemented – simulation error detected and working on it. (status: 80%)
O6.4. Algorithm developed and expected to work on O6.3 completion. (status: 80%)
O6.5. Initial hypothesis of system reduction from 3D to 2D. (status: 5%)
O7. Artificial intelligence. - We will employ classical statistical approaches and DL to distil and extract the relevant information from the RI images provided by the TPM, which will be crucial to manage such a large amount of data and will help during the LoC design and the training and validation of a reliable system. The developed AI algorithms will guarantee important predictive model features such as robustness, explainability, unbiased and trustworthiness.
The tasks related to this Objective have not yet begun.
O8. Laboratory demonstration of a device able to detect synthetic healthy cells and Urological Cancer (Uca) and Gynaecological Cancer (GCa) Tumour cells (TCs) based on the optimisation of the TPM microscope, the microfluidic system and DL algorithms of O4-O7.
The tasks related to this Objective have not yet begun.
O9. Laboratory demonstration of a device able to detect individual cells infected with viruses or bacteria in a heterogeneous population based on the results of O5-O7.
The tasks related to this Objective have not yet begun.
In this preliminary phase of the project, we have yet to yield tangible results. However, significant progress has been made in the technical aspect, yielding initial outcomes concerning the tomographic diffraction algorithm, as well as the design and manufacture of the initial nanoantennas that will form the circular detection hub. These nanoantennas are the critical component of our photonic holographic detector. Moreover, we have commenced the design phase and the establishment of the principal guidelines that will define the microfluidic system. This system will facilitate the flow of cells of interest to be tomographed in the project's final phase. We would also like to highlight that, although our project has been operational for only a year, we have achieved significant presence and development in Communication and Dissemination tasks. Regarding communication, we have undertaken various actions such as the generation of over 60 press releases, project branded materials, the creation of our website, and the design of different versions of a logo for the project. In the audiovisual segment, we have featured in multiple interventions on both radio and television with interviews and reports. Pertaining to dissemination, we have had a presence at an international conference and co-organised a workshop in collaboration with the Polytechnic University of Valencia.