Laser Nano-Neurosurgery from Gentle Manipulation to Nano-Incision of Neuronal Cells and Scaffolds: An Advanced Neurotechnology Tool

Abstract

Current optical approaches are progressing far beyond the scope of monitoring the structure and function of living matter, and they are becoming widely recognized as extremely precise, minimally-invasive, contact-free handling tools. Laser manipulation of living tissues, single cells, or even single-molecules is becoming a well-established methodology, thus founding the onset of new experimental paradigms and research fields. Indeed, a tightly focused pulsed laser source permits complex tasks such as developing engineered bioscaffolds, applying calibrated forces, transfecting, stimulating, or even ablating single cells with subcellular precision, and operating intracellular surgical protocols at the level of single organelles. In the present review, we report the state of the art of laser manipulation in neuroscience, to inspire future applications of light-assisted tools in nano-neurosurgery.

Advanced Biophotonics Techniques: The Role of Optical Tweezers for Cells and Molecules Manipulation Associated With Cancer

“…This advanced scientific field refers to the research and development of novel technologies, biosensors, and drug delivery systems for prevention, diagnosis, and treatment of diseases at the nanoscale, in sub-cellular and molecular level and for the dream of personalized therapy [7]. Moreover, laser-based techniques and instrumentation have driven to a new era in cell biology, the intracellular nanosurgery [8]. This technology has allowed the ability to perform precise nano-incisions in cells and manipulation of intracellular structures or even at the level of individual genes within the nucleus [9].…”

Modulation of Neural Network Activity through Single Cell Ablation: An in Vitro Model of Minimally Invasive Neurosurgery

“…Therefore, even if they provide high control and precision to perform small incisions, accurate confinement of the ablation volume is not achievable [41]. Otherwise, a new generation of femtosecond or picosecond pulsed laser sources provides a non-thermal regime of tissue ablation based on non-linear absorption of light, achieving a precision beyond the diffraction limit [42], and thus exploitable to perform single cell or intracellular surgery [6]. In the present work, we adopted a UVA picosecond laser source, to evaluate the effects of single cell ablation on the overall activity of a neural network.…”

“…In this work they described three distinct mechanisms of laser ablation: direct vaporization, pressure shock waves, and non-thermal photo-ablation [5]. After this seminal work, other laboratories applied laser dissection on in vitro cultures with distinct laser sources [6]. Laser sources with pulse duration in the sub-nanosecond regime have been exploited to better localize the ablation volume and restrict the affected portion of the sample [7].…”

“…Only recently the use of extremely ultrashort femtosecond laser (a few tens of femtosecond pulse length) has decreased the power necessary to perform laser ablation [13]. However, compact pulsed laser sources [6] can be easily integrated in optical systems at reasonable cost, with respect to ultrafast laser sources which also require complex and expensive maintenance.…”

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

“…The latter are deployed to guide cell process elongation in specific directions and mimic cell orientation, which, in turn, promotes coordinated spiking activity as seen in native brain tissue. Patterning can be achieved via diverse approaches [ 105 ], including photo-chemical cross-linking [ 84 ], photo-ablation [ 84 , 91 ], and bioprinting [ 89 , 99 , 106 , 107 ]. 3D scaffolds are suitable to generate multiple co-cultures within the interconnected porous structure, promoting the development of more complex organizations of neuronal networks.…”