OPTICALBRAIN - Filtros óticos de Fabry-Perot baseados em filmes finos e µ-lentes de coating de PDMS para probes neuronais

Coordinator: J. H. Correia

Workteam: João Ribeiro, Sara Pimenta, José Artur Rodrigues, Nuno Dias, Graça Minas, Marino Maciel, João Oliveira, Alexandre Silva, José Pereira, Sandra Gonçalves, João Freitas, Bruno Esteves

Funds: 239.497,06 €, PTDC/CTM-REF/28406/2017 FCT-Portugal

R&D Center: CMEMS-UMinho

Start: 26 July 2018. End: 28 February 2022

Summary:

The employment of MEMS technology for neural probes production, capable of interfacing with the central nervous system at the cellular level, is a reality. Optogenetics probes represent devices optimized for light delivering into a cell population, genetically modified, to produce a specific biological effect. Moreover, the combination of optogenetics with fluorescence emission magnifies the profits of neural probes, where the neurons are activated by light, photostimulation (PS), and their physiological status is also determined using light and fluorophores co-electroporated into the neurons. Introducing µ-LEDs and an array of photodiodes on a neural probe enables simultaneously: PS of different target neurons in the brain volume; excitation of fluorophores; and measurement of the emitted fluorescence, which indicates the neurons status. However, two major problems emerge: 1) the optical signal measured by the photodiodes must be the emitted fluorescence and not the neurons PS and fluorophores excitation lights (from the µ-LEDs); and 2) the µ‑LEDs emission irradiance needs to be at least 1 mW/mm2 for neurons PS, leading to the requirement of increasing the µ‑LEDs power, which presents another issue with high-power consumption and neurons overheat.

The OpticalBrain project proposes: the implementation of a high-selective Fabry-Perot optical filter (thin-films multilayer) and a coating of polydimethylsiloxane (PDMS) as µ-lens on the top of an array of photodiodes; and the empowering of µ-LEDs using PDMS µ-lenses. The optical filter on the top of the array of photodiodes (with a narrow full‑width‑half‑maximum (FWHM) of ≈ 10 nm) may be selective to the emission peak of GECOs (that fluoresces when bound to Ca2+) in order to measure the physiological Ca2+ dynamics of neural cells after the cells PS using the opsin ChR2 (Channelrhodopsin-2). The PDMS µ-lenses will allow the light collimation, optimizing the incident light in the array of photodiodes and the emission irradiation of the µ‑LEDs. Finally, the high selective array of photodiodes and the empowered µ-LEDs will be integrated in a neural probe.

The expected original contributions for neural probes are:

- To implement a high-selective Fabry‑Perot optical filter on the top of an array of photodiodes.

-To develop an implantable µ-lens on an array of photodiodes, that will optimize incident light without increasing the probe size.

-To develop implantable µ-lenses on µ-LEDs, that will increase the emission irradiance of by at least 10% without overheating the brain;

 -To establish a robust and adaptable manufacturing technology based in photoresist patterning for fabricating µ‑lenses on top of any array of photodiodes and µ-LED;

- To reduce the power consumption since the µ-LEDs emission irradiance is optimized with µ‑lenses.

-Developing flexible delivery probes for enabling reaching lesions in hollow organs of the human body via endoscopes;

-Optimizing laser power in Raman probes to be used real-time in-vivo for maximum permissible exposure and temperature increase avoiding tissue damage.

 

The final project results:

Patents

- An European Patent -  EP21188953, submtted on 30 July 2021, Neuronal device for optogenetic applications and neuronal activity monitoring in an animal and its use. Authors: Sara Pimenta, José Rodrigues, Eliana Vieira, João Freitas, Bruno Esteves, J. H. Correia.

 

- A Portuguese Patent -  PT116977, submitted on 28 December 2020, Dispositivo neuronal para aplicações optogenéticas e monitorização da atividade neuronal de um organismo animal e o seu uso. Authors: Sara Pimenta, José Rodrigues, Eliana Vieira, João Freitas, Bruno Esteves, J. H. Correia.

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PhD Theses

-PhD thesis, Sandra Beatriz Gonçalves, “µLED Optrode for Acute Optogenetic Applications”, Programa Doutoral MIT-Portugal, February 2019.


- PhD thesis, José Artur Rodrigues, “Terapia em dispositivos médicos invasivos com imagem”, Programa Doutoral Eng.
Biomédica, February 2019.

- PhD thesis, Francisca Araújo Guedes Machado, "Low Intensity Focused Ultrasound Modulation of Neuronal Circuits Activity", Programa Doutoral Eng. Biomédica, November 2019.

 

- PhD thesis, Ana Patrícia Tavares Moreira, "Development of biosensor integrated into Dye sensitized solar cell for measure cancer biomarker", Programa Doutoral Eng. Biomédica, December 2019.

 

Master Theses

-MSc thesis, Nuno Miguel Santos Teixeira de Sousa, “Fabrico de um Sistema para Eletrodeposição de Filmes Finos de Platina”, Mestrado Integrado em Eng. Eletrónica Industrial e Computadores, November 2018.

-MSc thesis, José Pedro de Oliveira Pereira, “Fabrico de um Filtro Ótico Integrado numa Matriz de Fotodíodos de Silício para Aplicação em Sondas Neuronais, Mestrado Integrado em Eng. Eletrónica Industrial e Computadores, November 2018.

-MSc thesis, João Rui Martins Freitas, “Fabrico de Microlentes para Aplicação em MicroLEDs”, Mestrado Integrado em Eng. Eletrónica Industrial e Computadores, November 2019.


- MSc thesis, Ana Cláudia Ferreira, Rectification, amplification and switching capabilities for energy harvesting systems, Mestrado Integrado em Eng. Biomédica, USN-Noruega, July 2020.

- MSc thesis, Diogo Azevedo Pereira, Sistema de comunicação ótica para dispositivos biomédicos, Mestrado Integrado em Engenharia Biomédica – ramo de Eletrónica Médica pela Universidade do Minho, February 2021.

 

- MSc thesis, Bruno Miguel C. Esteves, Fabrico e caracterização de um fotodetetor para integração numa sonda neuronal flexível, Mestrado Integrado em Engenharia Biomédica – ramo de Eletrónica Médica pela Universidade do Minho, March 2021.

 

- MSc thesis, Hugo Martins Pereira, Magnetómetros atómicos de bombeamento ótico para medição de campos magnéticos cerebrais, Mestrado Integrado em Engenharia Biomédica – ramo de Eletrónica Médica pela Universidade do Minho, March 2021.

International Conferences:

M. J. Maciel, S. Pimenta, J. F. Ribeiro, and J. H. Correia, “Design of a novel TiO2/Airgap-based polarizing micro beam splitter cube,” in 29th Micromechanics and Microsystems Europe Workshop (MME 2018), August 26-29, Smolenice, Eslováquia, 2018.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2018_mmaciel.pdf

JF Ribeiro, S Pimenta, HC Fernandes, SB Goncalves, MR Souto, AM Goncalves, NAP de Vasconcelos, P Monteiro, JH Correia, “Low-cost Non-etched Silicon Neural Probe”, 9th International IEEE EMBS Conference on Neural Engineering (NER’19), San Francisco, CA, USA, March 2019.

URL: https://doi.org/10.1109/NER.2019.8716910

M. J. Maciel, M. F. Silva, S. Pimenta, and J. H. Correia, “Detection of low-magnetic fields by rubidium (87 Rb) vapor cell,” Proceedings MME 2019 Micromechanics and Microsystems Europe Conference, Oxford. UK, pp. 7–12, 2019.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2019_mmaciel.pdf

M. F. Silva, S. Pimenta, J. A. Rodrigues, M. J. Maciel, M. Ghaderi, L. M. Goncalves, G. de Graaf, R. F. Wolffenbuttel, J. H. Correia,” UV optical filters based in magnesium”, Proceedings MME 2019-Micromechanics and Microsystems Europe Conference, Oxford. UK, pp. 73–78, 2019.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/mme2019_msilva.pdf

S. Pimenta, M. Maciel, A. Miranda, M. Cerqueira, P. Alpuim, and J. Correia, “Raman Spectroscopy for Tumor Diagnosis in Mammary Tissue,” in Proceedings of the 8th International Conference on Photonics, Optics and Laser Technology, Photoptics, pp. 131–134, La Valleta, Malta, 2020.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/photoptics2020_spimenta.pdf

International Journal Papers:
AC Costa, S Pimenta, JF Ribeiro, MF Silva, RF Wolffenbuttel, T Dong, Z Yang, JH Correia, “PDMS microlenses for focusing light in Narrow Band Imaging diagnostic”, Sensors, MDPI, vol. 19, No. 1057, March 2019.

https://doi.org/10.3390/s19051057

S Pimenta, JP Pereira, NM Gomes, JF Ribeiro, MF Silva, SB Goncalves, G Minas, JH Correia, “High-selectivity neural probe based on a Fabry Perot optical filter and a CMOS silicon photodiodes array at visible wavelengths”, J Biomed Opt, SPIE, vol. 23, pp. 105004, October 2018.

 

URL: https://doi.org/10.1117/1.JBO.23.10.105004

SB Goncalves, JM Palha, HC Fernandes, MR Souto, S Pimenta, T. Dong, Z Yang, JF Ribeiro, JH Correia, “µLED optrode with integrated temperature sensing for optogenetics”, Micromachines, MDPI, vol. 9, No. 473, September 2018.

 

URL: https://doi.org/10.3390/mi9090473

SB Goncalves, AM Loureiro, HC Fernandes, S Pimenta, JF Ribeiro, JH Correia, “High-aspect ratio Si neural shafts: fabrication and brain implantation”, J. Microelectromech. Syst, IEEE, vol. 27, No. 6, December 2018.

 

URL: https://doi.org/10.1109/JMEMS.2018.2868229

M. J. Maciel, S. Pimenta, J. F. Ribeiro, and J. H. Correia, “Design of a novel TiO2 /airgap-based polarizing micro beam splitter cube,” J. Phys. Conf. Ser., vol. 1319, no. 012006, Sep. 2019.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/jphycs_2019_mmaciel.pdf

M. J. Maciel, N. M. Gomes, S. Pimenta, J. F. Ribeiro, and J. H. Correia, “TiO2/airgap-based polarizing beam splitter: design, simulation, and fabrication based on MEMS technologies,” Opt. Lasers Eng., vol. 133, no. 106110, Oct. 2020.

URL: https://www.sciencedirect.com/science/article/pii/S0143816619308814?via%3Dihub

S. Pimenta, S. Cardoso, E. M. S. Castanheira, G. Minas, "Towards an on-chip optical microsystem for spectroscopic detection of gastrointestinal dysplasia". Sensors & Actuators: B. Chemical, Vol. 281, pp. 751-756, 2019.

URL: http://dei-s2.dei.uminho.pt/outraslic/OCTRAMAN/sa_b_spimenta.pdf

- J. A. Rodrigues, S. Pimenta, J.P. Pereira, J.H. Correia, Low-cost silicon neural probe: fabrication, electrochemical characterization and in vivo validation, Journal Microsystem Technologies, Springer, May 2020.

URL: https://doi.org/10.1007/s00542-020-04898-3

M. F. Silva, S. Pimenta, J.A. Rodrigues, J. R. Freitas, M. Ghaderi, L. M. Goncalves, G. de Graaf, R. F. Wolffenbuttel, J.H. Correia, Magnesium fluoride as low-refractive index material for near-ultraviolet filters applied to optical sensors, Journal Vacuum, Vol. N., pp.-, August 2020.

https://doi.org/10.1016/j.vacuum.2020.109673

J. R. Freitas, S. Pimenta, J. F. Ribeiro, Tao Dong, Z. Yang, J. H. Correia, “Simulation, fabrication and morphological characterization of a PDMS microlens for light collimation on optrodes", Journal Optik,  Vol. 227,  article 166098, 1-8 pages, February 2021.

https://doi.org/10.1016/j.ijleo.2020.166098

 

Bruno Esteves, S. Pimenta, Eliana Vieira, J.F. Ribeiro, J. A. Rodrigues, J. H. Correia, “SnOx and a-Si thin-films based photodiode in a flexible substrate for visible spectral region ", Journal Materials Letters,  Vol. 286,  article 129251, 1-4 pages, March 2021.

https://doi.org/10.1016/j.matlet.2020.129251

 

S. Pimenta, J. A. Rodrigues, F. Machado, J. F. Ribeiro, M. J. Maciel, O. Bondarchuk, P. Monteiro, J. Gaspar, J. H. Correia, L. Jacinto, “Double-layer flexible neuronal probe with closely spaced electrodes for high-density in-vivo brain recordings, Frontiers in Neuroscience, 15, 663174, 2021.

 

https://doi.org/10.3389/fnins.2021.663174

 

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