TP2 - Application Specific Integrated Microscopy (ASIM) based on tailored μLED systems

Neurons are highly compartmentalized cells in which sub-compartments, like axons and dendrites, are dedicated to a specialized biological and metabolic function, enabling them to receive or transmit information. Each sub-compartment forms its own locally controlled environment to maintain itself, to fulfil its function and to cooperate with other compartments of the neuron.

In order to investigate the local processes in axons and dendrites in more detail, high resolution optical microscopy is a powerful tool which is generally used also in the investigation of homeostatic processes, with which the cell is stabilizing its equilibrium by self-regulation. However, due to the complexity of the instrumentation, conventional optical microscopy is unable to observe living cells in vivo in a compact, regular incubator environment. At the same time, conventional microscopy cannot image macroscopically long cells with highest optical resolution, since high optical resolution is typically accompanied by a small field-of-view. These restrictions of conventional microscopy are particularly limiting when axons and dendrites are to be investigated.

The investigation of neurological processes places high demands on measurement methods and instruments. The active optical components used should provide detailed information with as little damage as possible and be usable simultaneously with other stimuli or measuring instruments. The innovative approaches necessary to tackle this challenge will through high levels of integration and customization provide the key to understanding metabolic processes of the nervous system.

The processing of smallest light sources of a certain wavelength and their almost arbitrary arrangement into arrays of different dimensions is one of the core competences of the Institute of Semiconductor Technology [1],[2],[3]. Such light-emitting diodes (LEDs) can be used for various purposes, which in this project will also serve to study metabolic homeostasis.

Abbildung 2
(a) Neuroblastoma cell culture measured inside a cell incubator shown at the start of the measurement period; (b) cell culture after two days; and (c) confluence estimation over the cultivation period [5].

On the one hand, with the help of the locally very precisely confinable light emission, compact and robust imaging units can be implemented, which, according to the principle of lensless digital holography, enable the continuous observation of biological samples within commercially available incubators. With a resolution of currently 2.2 µm, cells can be imaged and their change and movement analyzed by image processing algorithms (see Figure) [4].

 

Prototyp eines linsenlosen Mikroskops.
A prototype of the microscope and the smarthpone application to operate it.

Prototype of a lensless microscope. The associated application for operating the microscope and displaying the image is shown on the smartphone.

 

µLED-Arrays mit unterschiedlichen Wellenlängen
µLED arrays with different wavelengths.

On the other hand, LEDs arranged in arrays offer the possibility of precise and locally highly resolved optical stimulation of biological samples. Different concepts for the use of structured light fields for optogenetic questions are investigated for this project and developed in an interdisciplinary way.

 

References

[1]    H. S. Wasisto, J. D. Prades, J. Gülink, and A. Waag, “Beyond solid-state lighting: Miniaturization, hybrid integration, and applications of GaN nano- and micro-LEDs,” Applied Physics Reviews, vol. 6, no. 4, p. 41315, 2019, doi: 10.1063/1.5096322.

[2]    J. Gülink et al., “InGaN/GaN nanoLED Arrays as a Novel Illumination Source for Biomedical Imaging and Sensing Applications,” Proceedings, vol. 2, no. 13, p. 892, 2018, doi: 10.3390/proceedings2130892.

[3]    V. Agluschewitsch, M. Garcés-Schröder, and A. Waag, “Optofluidic Particle Detection,” Proceedings, vol. 56, no. 1, p. 26, 2020, doi: 10.3390/proceedings2020056026.

[4]    A. B. Dharmawan et al., “Nonmechanical parfocal and autofocus features based on wave propagation distribution in lensfree holographic microscopy,” Scientific reports, vol. 11, no. 1, p. 3213, 2021, doi: 10.1038/s41598-021-81098-7.

[5]    G. Scholz et al., “Continuous Live-Cell Culture Imaging and Single-Cell Tracking by Computational Lensfree LED Microscopy,” Sensors (Basel, Switzerland), vol. 19, no. 5, 2019, doi: 10.3390/s19051234.

 

Contact

Prof. Dr. Andreas Waag
Technische Universität Braunschweig
Institute of Semiconductor Technology
Hans-Sommer-Straße 66
38106 Braunschweig
Germany
Phone: +49 531 391 3774
Email: a.waag@tu-braunschweig.de
www.tu-braunschweig.de/iht

Dr.-Ing. Mayra Garcés-Schröder
Technische Universität Braunschweig
Institute of Semiconductor Technology
Hans-Sommer-Straße 66
38106 Braunschweig
Germany
Phone: +49 531 391 65327
Email: m.garces-schroeder@tu-braunschweig.de
www.tu-braunschweig.de/iht