**Low-Cost Sensors and Biological Signals**

Editors

**Fr ´ed ´eric Dierick Fabien Buisseret St ´ephanie Eggermont**

MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin

*Editors* Fred´ eric Dierick ´ Centre National De Re´education ´ Fonctionnelle et de Readaptation ´ Luxembourg Universite catholique de ´ Louvain Belgium CeREF-Technique Belgium

Fabien Buisseret CeREF-Technique Belgium Université de Mons—UMONS, Research Institute for Complex Systems Belgium

Stephanie ´ Eggermont CeREF-Technique Belgium

*Editorial Office* MDPI St. Alban-Anlage 66 4052 Basel, Switzerland

This is a reprint of articles from the Special Issue published online in the open access journal *Sensors* (ISSN 1424-8220) (available at: https://www.mdpi.com/journal/sensors/special issues/LCSBS).

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**2. Red light transcranial LED therapy (RL-TCLT): types, devices, uses, and effects**

The use of transcranial photobiomodulation is promising in therapeutic and medical benefits for health, with increasing application and projection also in aging and neurodegenerative diseases [9, 24, 25]. The light presents different characteristics that could be used advantageously in the field of health, principally by recent

lighting technologies based on an extensive range of diverse light sources, that have been used for photobiomodulation [8]. Light for therapeutic purposes corresponds to a small fraction of the spectrum of luminous radiation, generally in the visible spectrum [8, 25], where it has a biological effect based on the premise of mammalian cellular metabolism from photoreceptors and chromophores molecules [25].

Diverse devices have been used, including Light Amplification by Stimulated Emission of Radiation (Laser) devices, Low-level light laser therapy, and lightemitting diodes (LED) devices [26]. LED devices are semiconductors that present a high efficiency of electrical energy conversion into optical energy, dissipating little thermal energy [26]. Furthermore, these devices can have widely fluctuating power levels depending on the size, number, and power of the individual diodes [16, 27, 28]. LED devices have been compared with lasers; however, devices irradiating LED are bandwidth (approx 40 nm), beam divergence, incoherent radiation emission, and high optical output power; favoring the absorption of energy by different molecular structures [5, 8]. In addition, LED devices have been considered as a safety by the US Food and Drug Administration (FDA) [29].

Red-Light Transcranial Led Therapy (RL-TLTC) involves power-efficient, low heat-producing light sources that have the potential to deliver high-intensity RL of 600-690 wavelengths, that can be pulsed or continuous [30]. In this therapy, the light goes through the layers of the skin and skull, to stimulate the brain and specific cerebral regions, causing biological responses that result in benefits for the individual [7, 8, 31]. In particular, RL-LED mediated a vibrational absorption process, which produces a photochemical effect that leads to the absorption of photons by specific molecules in the cell [5]. In addition, the wavelength (nm), energy density (J/cm2 ), and power density (mW/cm2 ) are parameters that determine the effectiveness of RL-TLTC. The wavelength of light used is critical since not all ranges of light used have a similar effect, some ranges present reduced effects such as wavelength in the 700–750 nm range. In contrast, RL-LED at 600–690 nm or 760–900 nm has more impact on the biological tissues [5, 8]. Considering that these parameters of light radiation interact with biological tissue, they cause optical phenomena of reflection, transmission, propagation, and absorption. These characteristics also can present variations depending on tissue irradiated, for example by different concentrations of photoreceptor and chromophores molecules that contain biological tissues, like water, cytochromes, and organic molecules as flavins, hemoglobin, and melanin, among others [5]. When light is absorbed, the photon energy reaches the target molecules producing vibrational, rotational, or electronic processes, which generate diverse effects including photochemical, photo-thermal, photomechanical, or photo-electrical stimulation [5].

Interestingly, in the use of RL-TLCT, no standard protocol has been established in the literature; moreover, a few reports have shown studies using diverse parameters as varied wavelength ranges, time (sec/min), irradiance, or power density, and energy density with similar results, and important benefits in the brain health [5]. For example, studies applying Transcranial LED therapy bilaterally with wavelengths of 633 and 870 nm, have shown significant progress in both animals models with acute traumatic brain injury, and patients with acute stroke. In both cases also have been observed an improvement in the cognitive capacity post-treatment with this therapy [20]. Other studies using Low-level Laser Therapy (LLLT), with parameters of energy of 3 J/cm2 , a wavelength of 810 nm, and power density of 20 mW/ cm2 , in primary cultured cortical neurons exposed to oxidative stress reveal that LLLT increased the mitochondrial membrane potential and reduced high ROS levels, reducing neuronal death [32]. Similarly, other studies showed that LLLT has a positive impact on neuronal function in both *in vitro* and *in vivo,* enhancing the metabolic capacity of neurons and cognitive functions including memory [14].

*Transcranial Red LED Therapy: A Promising Non-Invasive Treatment to Prevent Age-Related… DOI: http://dx.doi.org/10.5772/intechopen.100620*

Thus, while the transcranial research using RL LED or laser remains in the initial stages, growing evidence showed that although the RL and NIR-light therapy presents a wide range of characters, can modulate cell activity, including energy metabolism and cell function [25]. This is relevant since these therapies can lead to the improvement of pathological conditions and be in future significant clinical contribution, for example performing clinical treatments that allow helping older persons to prevent or mitigate the age-related cognitive impairment (**Figure 1**).


**1. Introduction**

A better understanding of the pathogenesis of autoimmunity makes it possible to select more specific therapeutic targets and design biological agents that can replace or enhance the effect of immunosuppressive drugs; these include monoclonal antibodies, soluble receptors and molecular mimetics. This chapter aims to give a brief summary on different protein-based medications: first on the biologicals targeting cytokines that induce inflammatory responses, then on drugs depleting B cells via CD20 and CD22 and finally, on agents that inhibit cell-cell contacts and block cell survival factors. Immunogenicity of these protein preparations causes a significant problem therefore the last section gives an overview of biotechnological approaches aiming to reduce this effect.


Sheep Farming - An Approach to Feed, Growth and Health

*Edited by António Monteiro*

Published in London, United Kingdom

## *Supporting open minds since 2005*

Sheep Farming - An Approach to Feed, Growth and Health http://dx.doi.org/10.5772/intechopen.78842 Edited by António Monteiro

#### Contributors

Hamidou Nantoumé, Samir Medjekal, Mouloud Ghadbane, Tadesse Sisay Amare, Gebeyehu Goshu Negia, Berhan Tamir Mersso, António Cardoso Monteiro, Sérgio Santos, José Manuel Costa, Fernando Esteves, Luis Miguel Ferrer, Juan Jose Ramos, Delia Lacasta, Enrique Castells Perez, Héctor Ruíz, María Climent

#### © The Editor(s) and the Author(s) 2021

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Individual chapters of this publication are distributed under the terms of the Creative Commons Attribution 3.0 Unported License which permits commercial use, distribution and reproduction of the individual chapters, provided the original author(s) and source publication are appropriately acknowledged. If so indicated, certain images may not be included under the Creative Commons license. In such cases users will need to obtain permission from the license holder to reproduce the material. More details and guidelines concerning content reuse and adaptation can be found at http://www.intechopen.com/copyright-policy.html.

#### Notice

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**2. Interaction of Nanoparticles with Cell Membrane**

The shape and biological functions of membranes can be strongly influenced by attached, encapsulated (Figure 1) [30], or intercalated inclusions such as nanoparticles (NPs). Unique optical, electronic, catalytic, and magnetic properties of NPs make them very interesting for a variety of biomedical applications [1,31–34]. For example, functional NPs and quantum dots are potential candidates for drug delivery, as well as carriers for cancer therapy [33,35]. When NPs interact with cells, the first barrier that NPs encounter is the plasma membrane. Intra- and extracellular transport of NPs are possible by a dynamic membrane shape transformation that involves a change in the membrane curvature (encapsulation) [30,32,33,36] (Figure 1). Membrane deformations may progress passively, that is, without employing an additional energy source, driven solely by the interaction between the membrane and NPs. Viral budding comprises such an example [37]. The intracellular entry of genetic material is presently receiving considerable attention due to the COVID-19 crisis. Electrostatic interactions [38,39] may facilitate NP or virus internalization via encapsulation [30,33] (Figure 1). Understanding the interplay between the membrane elastic and electrostatic properties of the NP–membrane complex, toward the encapsulation of NPs by the cell membrane, is also relevant for cellular drug uptake, viral budding, biotechnological applications, and studying the interactions of inorganic NPs with biological membranes [32,33].

**Figure 1.** Encapsulation of a spherical charged particle macro-ion. Snapshots of representative configurations obtained from Monte Carlo simulations for different numbers of charged lipids (each having one unit charge) in the membrane: 15, 60, and 150 (from left to right). The right figure corresponds to the situation of nearly complete encapsulation of the macro-ion. The spherical particle carries 65 uniformly distributed, point-like cations of valence 2. Reprinted from [30] with permission of AIP Publishing.

Another possible interaction of NPs with the membrane is the attachment (adsorption) of the former on the membrane surface [34,38,40], encapsulation [30], or their intercalation in the membrane [41–43]. The resulting configuration could be driven by the NP shape, charge, size, and stiffness; it also depends on the nature of the NP–membrane interaction [30,34,38,39,41,44]. For example, hydrophobic or cationic NPs with diameters smaller than 5 nm can be successfully embedded within the membrane bilayer. On the other hand, anionic NPs of the same size or larger NPs can only interact with the outer surface of the membrane [45]. NPs interacting with membranes may induce lateral tension that results in pore formation, either transient or permanent; the pores are actually stabilized by NPs. Nanoparticles could also cluster within the membrane, and the resulting change in the membrane mechanics could significantly influence its biological function and could even result in membrane disruption [46]. Simulations demonstrated that the properties of both the membrane and the NPs are equally important in explaining the membrane uptake of the latter [30,41].