Periodic Reporting for period 1 - FUNPROBE (Multifunctional Nanoscale Probe for Investigation of Intracellular Processes)
Période du rapport: 2021-04-01 au 2023-03-31
The ability to monitor and investigate intracellular processes is crucial for biomedical, cancer and aging research, and has direct applications in disease diagnosis, and drug development. The investigation of such processes requires tools capable of accurate and quantitative monitoring of an array of dynamically changing physical and chemical properties in specific cells at subcellular resolution and with minimal disruption to the cell. Despite significant recent advances in the field, implementing multiple functions in a single device while maintaining the required subcellular spatial resolution is a major technological challenge, as the entire probing instrument tip should not exceed submicrometer dimensions. Therefore, existing tools are limited in their sensing capabilities to single properties. The main objective of FUNPROBE is to develop a novel fabrication process for a multifunctional nanoscale probe. To achieve this goal, a new fabrication process was developed, which enables, for the first time, the fabrication of high aspect-ratio sub micromerer tip with embedded open-ended nanochannels. Custom electro-opto-mechanical system and stage was created to enable probe positioning and visualisation on an inverted fluorescence microscope. The integration of conductive layers at the tip to create electrodes for thermal sensing and electrical recording remains to be implemented as part of the fabrication process in the future. The development of future multiplexed devices for cell-sensing at the nanoscale is in alignment with the European Commission's aims of developing multifunctional nanoenabled products for different applications.
Work was conducted via 3 work packages (WPs). WP1 comprised the development of a comprehensive and robust fabrication of the probing device. Multiple microfabrication challenges have been tackled and resolved. WP2 involved the development and design of a custom electro-opto-mechanical system for the accurate control of the probe on top of the surface-based sample on an inverted fluorescence microscope. WP3 was aimed at enhancing the knowledge transfer between the researcher and the host group by developing two novel techniques for highly sensitive detection of biomarkers. These techniques hold potential applications in medical diagnostics.
The main output of WP1 is the detailed process flow developed for the probe fabrication, which serves as a knowledge resource for current and future users of the EPFL Center of Microtechnology (CMi), and is published on the project’s public website. The main result of WP2 is a prototype of an accurate positioning and visualization system. WP3 resulted in a theoretical study and experimental proof-of-concept of two electrophoretic techniques based on isotachophoresis for (1) the detection of dopamine from brain fluid samples and (2) concentration and sorting of cells. Results of this project have been reported in two scientific conferences, one workshop, five annual conventions, an invited talk, and four public outreach events.
The main output of WP1 is the detailed process flow developed for the probe fabrication, which serves as a knowledge resource for current and future users of the EPFL Center of Microtechnology (CMi), and is published on the project’s public website. The main result of WP2 is a prototype of an accurate positioning and visualization system. WP3 resulted in a theoretical study and experimental proof-of-concept of two electrophoretic techniques based on isotachophoresis for (1) the detection of dopamine from brain fluid samples and (2) concentration and sorting of cells. Results of this project have been reported in two scientific conferences, one workshop, five annual conventions, an invited talk, and four public outreach events.
This project has pushed the frontiers of current knowledge in robust fabrication of nanodevices. The results have made substantial contributions to the progress of fabricating nanostructures, particularly high aspect ratio nanochannels integrated on a suspended cantilever. Our research has yielded valuable knowledge and insights into different facets of the fabrication process, leading to a comprehensive process flow for the reliable production of such devices. Additionally, we have designed a specialized electro-opto-mechanical system that enables precise positioning and control. A functional prototype of the positioning system has been successfully delivered, and the developed process flow is stored in the CMi database, serving as a valuable resource for current and future researchers and users of the cleanroom. The development of future multiplexed devices for cell-sensing at the nanoscale is in alignment with the European Commission's aims of developing multifunctional nano-enabled products for different applications.