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A huge influence of the groove spacing was observed. Various inorganic materials also showed thermal response. Shirtcliffe et al. To become hydrophilic, the surface must become more polar. The authors think that this could occur by the formation of new groups or by a change in the relative abundances of apolar methyl groups and polar silica species. The temperatures at which switching occurred were increased when larger fractions of PhTEOS and reversely. SiO 2 suspensions, made from SiO 2 nanoparticles hydrophobically modified with chlorotrimethylsilane and PDMS vinyl terminated, were deposited by spraying [ ].

Here, the authors attributed this possibility to water vapor condensation on the surface. When the subfreezing film was placed in ambient environment, the humidity in the air condensed to the subfreezing surfaces and increased the surface hydrophilicity. Otherwise, inorganic materials could also be coated using a hydrophobic material in order to achieve superhydrophobic properties [ , , , , ].

Here, the heat treatment could induce the desorption of the hydrophobic material and switch the surface from superhydrophobic to superhydrophilic. However, these kind of materials are reversible but only after surface remodification with the hydrophobic material.

Materials containing functional acid or basic groups such as amines or carboxylic acids can be used to induce switchable properties by pH changing [ , ]. Zhang et al. Depending on the surface roughness and the pH, it was possible to obtain switchable surface from superhydrophobic to superhydrophilic.

Indeed, the authors showed that the pressure that the meshes can support is depending on the mesh geometry and pore size, formation of surface structures on the meshes nanoneedles and the surface energy, which here changes with the pH [ , , , ].

For acidic and neutral water, the meshes were superhydrophobic and underwater superoleophilic. For basic water, the meshes were superhydrophilic and underwater superoleophobic.

Cu OH 2 nanoneedles grown on copper steel meshes. The resulting meshes could switch from superhydrophobic and underwater superoleophilic to superhydrophilic and underwater superoleophobic by changing the pH. The change of wettability of DNA nanodevices was also studied [ ]. The conformation of the DNA molecules on the substrate could change with the pH. The substrate was superhydrophilic at low pH and superhydrophobic at high pH. Various polymers with pH-sensitive groups were also used in the literature.

Polymers with carboxylic groups were reported [ , , , , , ]. Reversible change from superhydrophobic to superhydrophilic of colloidal crystals Panels A—D made of polymers with COOH groups as a function of the pH Figure on the right. These acids are diacids with a pKa1 between 1 and 2 and a pKa2 between 6 and 7 Figure Three different acids are present dependent on the pH [ , , ].

Poly methacryloyl ethylene phosphate PMEP brushes were used. Different species present using orthophosphoric acids as a function of the pH.

In order to induce basicity, amino groups were also highly used in the literature using different strategies [ , , ]. Among the basic groups, pyridine was also reported.

Wang et al. After casting the suspension particles on non-woven cellulose textiles and PU sponges, the resulting materials displayed superhydrophobic and underwater superoleophilic properties at pH 6.

Graphene foams with switchable oil wettability were also reported by grafting block copolymer brushes of poly 2-vinylpyridine- block -hexadecyl acrylate P2PV- b -PHA [ ]. By contrast, other authors chose to graft the polymer directly on substrates [ , ]. Luo et al. Finally, other authors used block copolymers with both acid and amino groups [ , ].

For example, Zhou et al. The best advantage of using electrical sensitivity as extern stimulus is the rapidity of implementation [ , ]. Among the most used materials, conducting polymers are extremely interesting because they can exist in different doping states.

The neutral dedoped state is uncharged, while the doped states are charged Figure Moreover, in their doped states, conducting polymers incorporated doping agents most of the time counter-anions in order to neutralize the charges present inside the polymer backbone.

Reversible change in the doping state of conducting polymers by oxidation and reduction [ ]. For example, smooth poly 3-alkylthiophene films prepared by spin coating were studied Figure 24 [ ].

The highest decrease from In order to enhance the wettability difference between the reduced and the oxidized state, the authors also deposited micro-patterned substrates. Then, they observed a much higher decrease from Influence of doping anions in the surface hydrophobicity of smooth poly 3-alkylthiophene.

Otherwise, various other techniques can be used to prepare structured conducting polymer films. Among them, using an electrochemical cell, the electropolymerization allows in one step having polymerization, deposition of conducting polymer film and obtaining of structured films. The surface structures are highly dependent on electrochemical parameters deposition method, time, solvent, electrolyte… and on the monomer used [ , , , , , , ].

For example, superhydrophobic rough polypyrrole films were reported by electropolymerization of pyrrole by galvanostatic deposition constant current of 0. Moreover, Chang et al. Other monomers were also studied [ , , , , , ]. Yan et al. Polyaniline is an interesting polymer because different chemical forms can be produced also depending on the pH.

In the presence of tetraethylammonium perfluorooctanesulfonate, the authors reported the possible switching from superhydrophobic emeraldine salt form to superhydrophilic leucoemeraldine base form by changing the voltage. Their electropolymerization was performed in acetonitrile and at constant potential. Porous films were obtained and the surface morphology was highly dependent on the electrolyte. By contrast, using poly 3-hexylthiophene , the surface could switch from superhydrophobic to parahydrophobic high water adhesion [ ].

The surfaces could also induce switchable cell adsorption [ ]. Advincula created first polystyrene colloidal crystals in hexagonal packing, on which a polythiophene film with short alkyl chains was electrodeposited by cyclic voltammetry [ ]. The surface could switch from superhydrophobic to highly hydrophilic. Here also, the protein and bacterial cell adsorption could also be switched at the same time [ ].

Otherwise, different strategies were employed to create nanostructured conducting polymers in solution. For that, polyaniline is a choice material due to the presence of amine groups that allow to induce self-assembly by hydrogen bonds [ , , , , , , ].

Nanoparticles were formed on the fabrics. Fabrics with switchable wettability from superoleophobic to superoleophilic were also reported using perfluorooctanoic acid [ , ]. The meshes could switch from superhydrophobic to superhydrophilic at different voltages. Metal ions and organic molecules sensitive to redox reactions can also be used to switch the surface wettability by voltage [ , ]. Huck et al. The reorientation of polyelectrolyte conformation is another phenomenon induced by electric potential [ , ].

Choi et al. The molecules in the straight conformation are hydrophilic due to the presence of carboxylate ions and that in the curved conformation are hydrophobic due to the presence of the hydrophobic chains.

Electrowetting is another method allowing the control of the surface wettability by applying an extern electric field. In this process, a water droplet is placed on a superhydrophobic surfaces coated with an insulating layer. Schematic representation of electrowetting experiment.

In , Krupenkin et al. After electrowetting, they could change the surface wettability from superhydrophobic to superhydrophilic. Vertically aligned superhydrophobic carbon nanofibers and ZnO nanorods were also highly used in the literature to induce a switch from superhydrophobic to hydrophilic or superhydrophilic [ , , , , ]. Boukherroub et al. They found a relationship between the resistance to drop impact impalement and electrowetting impalement Figure 27 [ ].

The thresholds for drop impact and electrowetting irreversibility increase and the contact angle hysteresis decrease when the length and the density of nanowires increase. Villagers willing to partake in a FGD provide their names to the research team, and may or may not be randomly selected to join the FGD organised for their age and gender group. Randomised selection of village FGD participants avoids burdening CHWs or other leaders with the task of identifying potential participants which could also potentially result in biased responses tied to particular village interests.

Also, in our experience, many are interested in participating in FGDs, and this randomised selection ensures all those interested have and know they have an equal chance of being selected names of volunteers drawn from hat at village meeting. Homosociality and age-group separation are dominant norms guiding social interaction in this part of Madagascar.

Hence, to facilitate participants feeling at ease and to limit the possibility of social hierarchies in a FGD over-determining who feels able to express their view in a group, FGDs are being organised along age and gender lines: married men, married women, unmarried men, unmarried women, elder men and elder women table 1.

FGDs are run using a standard set of questions organised into two parts. Recruitment is purposive and targets five categories of key stakeholders in each village 1 DrOTS project-enrolled adult patients over 15 years of age 2 adults who presented for TB testing to the DrOTS team but have received negative diagnostic testing results 3 villagers hesitant, unable or have declined to join the project 4 CHWs 5 village leaders, including kings and elected district chiefs.

An estimated eight interviews will be performed in the same subset of three villages as FGDs for a total of 24 interviews table 2.

Additional interviews are performed with TB confirmed cases outside the included villages to increase the number of DrOTS-enrolled patients. An anthropology trainee will seek permission to stay with one DrOTS patient in their village over a 2-week period in order to better understand, through ethnographic observation, how that individual lives with TB disease on a daily basis and interacts with DrOTS. Ethnographic observation often occurs over a period of months or even years; however, even shorter applications of this method can build contextual understanding of healthcare projects.

Use of this method in this study may confirm or reveal gaps in the information gathered through the other data collection methods, and serve to identify questions for future research. Interviews and FGDs will be transcribed and translated into English by a professional Malagasy translator mastering the field study site local dialect.

Transcripts will be uploaded into Nvivo V. Categories of enquiry in interview and FGD guides will form the basis for an initial coding structure. Three semistructured interviews will then be independently coded by two investigators to test and adjust this structure in light of the data, adding themes to account for unanticipated but relevant content. In an iterative process, minor adjustments and additions eg, change in theme names or merging of themes to the codebook will be made when needed.

Key theme and subtheme contents will be summarised and reviewed to allow linkage of quantitative and qualitative data, clearly identify themes with exemplary quotes, raise questions and concerns, and inform guidelines for culturally and contextually sensitive technology implementations. Following project and technology sensitisation visits and in accordance with cultural norms, consent is obtained from the local leaders to present this research project to villagers under their responsibility before engaging in any activities within villages.

Though limited literacy is widespread in this region of Madagascar, as per national research ethics norm, consent forms are read and explained to participants and written informed consent is obtained from any and all parties agreeing to participate before conducting interviews, focus groups and observations.

Participants in this perceptions study do not face any different healthcare as a result of participation. One issue that requires managing in such a study is the risk of social stigma for participants. TB and association with TB are stigmatised in contexts around the world, and well documented in sub-Saharan Africa eg, 3 4 23—25 While there is no evidence of TB stigma in the Malagasy context of our research, we are adopting strategies to mitigate the risk of TB-related stigma developing for participants in our TB-focused study.

In our initial meeting with CHWs in each village, we are stressing our interest in speaking with DrOTS-enrolled patients TB active but also our commitment to keeping the TB-active status of these patients private. We will be working with CHWs in villages to identify strategies to protect the TB-active status of any patients we interview. We will not carry out the ethnographic observation component of this study if doing so risks rendering public a currently private TB diagnosis.

Results of the DrOTS perception study will be submitted for peer-review publication. A two-page summary of results will be prepared in French and Malagasy and included as an appendix to the results paper, and shared with participants and collaborators for whom we have contact information. This study responds to a current gap in knowledge on the feasibility and cultural acceptability of using a new suite of technologies including evriMED, drones and tablet-mediated video education to support improved TB diagnosis and treatment in remote populations.

Digital technologies that enable remote monitoring and faster delivery of medical care and supplies are potential game changers for healthcare landscapes struggling with long-standing or temporary eg, due to disasters barriers to healthcare delivery. Still, the development of innovative healthcare technologies does not guarantee their enthusiastic and rapid adoption in diverse settings.

These may vary depending on any number of factors, including to name just a few the presence or lack of alternative options for care, association of use with a context-specific stigmatised condition, as well as prior direct or rumoured experiences with interventions deemed to be similar in some way to the new ones.

While focused on one project in Madagascar, the DrOTS perception study provides a model for attending to contextual factors that may affect target population support and intended interactions with any number of other new public health initiatives around the world. Embedding such perception studies within projects is particularly important for initiatives conceptualised based on the theoretical but as of yet unproven potential of new technologies.

While findings from perceptions studies on new innovative technology-mediated health projects may not be readily generalisable, as each setting is unique, such studies can generate learning that is transferable to other settings by drawing attention to the range of factors that may impact on technology adoption and interaction, and by shedding light on how others on the front line of innovative projects have sensitively navigated the cultural, social, political and ethical complexities of particular contexts.

The significance of results from this study will be difficult to ascertain given limited research on drone supported TB or other public health programmes at this juncture. Future research on similar programmes introduced in Madagascar or elsewhere will be helpful in assessing the generalisability of our eventual results to other regions and populations where such technologies for increased healthcare provision are being introduced.

Understanding rationales underlying government approval of pilot programmes such as DrOTS among individuals working for national TB control in the country, as well as the challenges and perception of outcomes and impact among these stakeholders constitute equally important research as we work towards clarifying what it means to develop context-appropriate use of innovative technologies in TB control.

Respondents may overemphasise positive perceptions of DrOTS. Social desirability bias is a challenge in perceptions studies, especially where there may be unspoken assumption among participants that their responses to study questions could negatively impact future programmes. We are grateful to the DrOTS project Malagasy team including community healthcare workers involved in patient and data management.

Contributors All authors meet criteria for authorship as per the International Committee of Medical Journal Editors recommendations. All authors have read and approved the final version of the manuscript before submission. Competing interests Authors declare no financial or personal relationships with other people or organisations that could inappropriately influence this work.

The authors have no relationship and obtained no funding for this study from the developers of evriMEDTM. The first and corresponding author had full access to all the data in the study and had final responsibility for the decision to submit this work for publication. Journal of extracellular vesicles Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles.

Biological Chemistry Current methods for the isolation of extracellular vesicles. International journal of molecular medicine Isolation of extracellular vesicles: Determining the correct approach Review. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction.

Frontiers in immunology Extracellular vesicles: potential roles in regenerative medicine. However, currently very few clinical validation studies and no 21 clearly defined manufacturing process exist. As exosomes progress towards the clinic for 22 treatment of a vast array of diseases, it is important to define the engineering basis for their 23 manufacture early in the development cycle to ensure they can be produced cost-effectively 24 at the appropriate scale.

We hypothesize that transitioning to defined manufacturing 25 platforms will increase consistency of the exosome product and improve their clinical 26 advancement as a new therapeutic tool. We present manufacturing technologies and 27 strategies that are being implemented and consider their application for the transition from 28 bench-scale to clinical production of exosomes. Broadly speaking, there are three main sub-classes of EVs: microvesicles that 35 are shed directly from the cell membrane and have a size range of nm diameter; 36 apoptotic blebs derived from dying cells, typically nm; and exosomes which are 37 smaller, with an approximate size range of nm — although this range is variable 38 between research groups [5]—[11].

Exosomes are released from multivesicular bodies MVBs 39 rather than directly from the cell membrane via exocytosis — a feature which distinguishes 40 these vesicles from other sub-classes [4], [12], [13].

This understanding has evolved based on the fact that implanted cells do not often 46 engraft or persist long-term, but rather, generate paracrine effects, which can be mediated 47 by exosomes transmitting information into resident tissue cells.

Indeed, post-injury tissue 48 regeneration studies have revealed that the regenerative effect of exosomes can be as potent 49 as that of parent cells in promoting regeneration and functional recovery in experimental 50 models including stroke [14], traumatic brain injury [15], pulmonary hypertension [16] and 51 wound healing [17]. The exosome cargo ensures continued 54 therapeutic effects long after the implanted cells have perished or migrated away from the 55 target site Figure 2.

For this reason, the potential applications of EVs in a 61 clinical context are diverse. Similarly, they might be used as biomarkers of infectious disease, 66 based on that fact that they transmit infection-specific elements. For example, exosomes 67 isolated from Huh 7.

For example, they are able to transfer RNA and protein 71 instructional cues from producing cells to other cells in the surrounding milieu [18].

This can 72 have striking effects, as evidenced from experiments where EVs derived from mouse 73 embryonic stem cells promoted the survival and expansion of mouse hematopoietic stem 74 cells in vitro, while also upregulating transcription factors associated with pluripotency in 75 recipient cells [28].

These findings also suggest that exosomes can be potentially harvested, 76 purified and potentially used as a biologic to control undesired or pathophysiologic 77 conditions.

For example, exosomes isolated from 79 indoleamine 2,3-dioxygenase-positive dendritic cells were found to reduce inflammation in a 80 mouse model of collagen-induced arthritis [29]. In both models, functional recovery was accompanied by cellular and molecular 92 evidence of neurogenic and angiogenic regeneration. For example, in the mouse model, MSC- 93 derived EVs of undisclosed size were able to support neuronal survival and neurogenesis in 94 the post-ischemic tissue to a level similar to that of parent MSCs, as measured from co- 95 expression of markers of cell division and identity [14].

This also translated into improved 96 motor coordination function in the animals. These include the use of autologous, modified dendritic-derived EVs for maintenance immunotherapy [32], [33], allogeneic MSC-derived EVs for the treatment of chronic kidney disease [34], type I diabetes mellitus clinical trial NCT , acute ischemic stroke clinical trial NCT , and autologous plasma- derived EVs for cutaneous wound repair clinical trial NCT In addition, a single patient with graft versus host disease was treated with allogeneic MSC-EVs [35].

Existing data from these trials indicate that exosomes may have potential therapeutic value in a number of indications without having necessarily met the primary trial endpoint. However, it should be noted that across these small number of studies, a variety of purification methods have been utilized, including filtration, ultracentrifugation and PEG precipitation, which may well impact the consistency of the final products.

Presumably, cellular changes due to transitioning from conventional bench-scale cell culture using planar t-flasks to scalable cell culture platforms might likely alter the composition and function of its exosomes. Large scale stem cell cultures are still a rate-limiting step for delivering stable and potent products at phase III and market scale due to high development costs and regulatory and market uncertainty [36]—[41].

Accordingly, the opportunities for producing large quantities of stem cell-conditioned medium with which to undertake meaningful scale-up studies on exosome production are limited [42]. This was evident in the worldwide survey conducted by Gardiner et al. The main technical limitation of these technologies, is the need for control of environmental parameters within the reactors such that the phenotype of the cell and derivative exosomes does not change.

When moving from static, planar cultures to dynamic, well-mixed 3D environments with high force generation impellers, cavitation of bubbles from oxygen sparging , the risk of phenotypic alterations at the cellular level due to shear stress is still an issue that needs to be addressed.

In the case of MSCs, a prominent candidate cell type for the production of candidate therapeutic exosomes, shear stress was found to induce mechanotransduction pathways involving p38 mitogen-activated protein kinase and extracellular signal-related kinase, that could lead to osteogenic differentiation [48]; these outcomes would likely change the exosome product, although this remains to be directly demonstrated.

Apoptotic blebs overlap in size and might increase heterogeneity, as well as reduce the potency of exosome products [49], [50]; an example of this heterogeneity was shown in a study conducted on between dendritic cell derived apoptotic vesicles and exosomes, that exosomal fractions had their own unique molecular composition and properties [51].

They might even induce undesirable cell signaling events, although this warrants further investigation. A key practical benefit in this approach is that these reactor systems can be designed and optimized to retain the exosome product within the culture compartment to yield a more concentrated conditioned medium, thereby reducing liquid handling requirements further downstream [52].

However, if exosomes are harvested before cultures are over-confluent, they might better conserve product parameters as they provide a similar mode of culture to planar t-flasks, unlike dynamic bioreactor systems. For example, fetal bovine serum FBS is high in endogenous exosomes [55], and if not removed prior to cell culture, these process- related impurities may make their way into the final drug product, which from a regulatory standpoint for an injectable, is completely unfavorable.

Therefore, xeno-free culture media components are desired, provided they conserve comparable cell characteristics and exosome product attributes that are expected to be therapeutic. However, this task is not trivial. At the very least, exosome-depleted FBS should be characterized as a means of confirming it is truly the stem cell-derived exosomes that confer the functional properties ascribed to them.

Specifically, both human and mouse neuroblastoma lines showed that switching from FBS-containing to serum-free medium left the resultant exosomes from both species unchanged in terms of biophysical and size characteristics [35].

However, the number of exosomes generated was increased when using serum-free reagents. While this may appear promising, further proteomic analysis showed that the serum-free exosomes contained reactive oxygen species and stress related proteins, whereas exosomes derived from cells cultured in serum-containing medium promoted higher levels of production of RNA processing proteins.

As a result, the switch from FBS-containing medium to serum-free appeared to cause a shift in exosomal biology, presumably reflecting stress-induced phenotypic changes in culture [56]. This overcomes one of the main challenges for adherent cell products, which need to be enzymatically detached from microcarriers, where harvesting and recovery are achieved with limited efficiency due to the need to conserve the cells for application whilst ensuring damage from extended enzyme exposure is limited [57].

Here, four main isolation methods are used: size exclusion based on typical exosomal diameters ; sedimentation force or flotation density; [non-specific] precipitation based methods; and affinity based capture. Two main variations of ultracentrifugation are used.

In spite of these protocols however, co-isolation of non-exosomal vesicles and other particulate debris that share similar size and density is still observed. The reasons for this — which may be applied directly to the future of exosome processing– are largely due to the high level of skill and manual labor gradient generation, sample balancing and pellet resuspension, all of which must be performed to high levels of precision , the time-intensive nature of the processes, the associated costs of reagents and equipment, and the observations of losses in potency of labile products.

This leads to a requirement for additional pelleting steps, which increases operating costs, purification times and product losses due to process inefficiencies and aggregation [64], not to mention losses in biological activity [65]. To address manufacturing and regulatory uncertainty here, further advancements are needed. However, these technologies may not be appropriate for larger scales.

By way of illustration, the large pore sizes of the resins used will likely present challenges related to pressure limitations and compression at larger scales.

One study showed that it was possible to make columns rather than rely on kits, and as similar levels of purification are achieved, the convenience of the kits far surpassed that of the columns [66]. Critically, one may also wish to enrich an exosome sub-population to increase the efficacy of a therapeutic which, with current technologies, is not possible using non-specific precipitation and sedimentation alone. This process is more promising than the sedimentation methods listed above, due to tight and reproducible size distributions and the ease with which processes can be scaled and can facilitate product washes and buffer exchanges [52].

This makes tangential flow filtration extremely attractive as a primary recovery method. Moreover hollow fiber ultrafiltration coupled with microfiltration is a relatively gentle process that retains structural and functional integrity of exosomes while enabling the removal of large particles and cell-culture derived proteins [61].

Excessive fouling leading to elevated pressure in the system, and consequent associated shear forces, could also be detrimental to the final preparation and must be carefully monitored. This often leads to co-isolation of non-exosomal vesicles or organelles with overlapping physical characteristics, resulting in insufficiently pure exosome preparations.

This was revealed when comparing density gradient and standard ultracentrifugation to an immuno-affinity capture method, as the latter increased exosome associated proteins by at least 2-fold over the ultracentrifugation options [70]. This can become particularly troublesome if large scale culture systems that lead to higher rates of cell death are employed in the future. A remedy to this potential burden would be the development of scalable processes which use methods of purification orthogonal to the current physical methods, i.

This need for reproducible and standardized platform technologies in the industry become apparent when literature searches for exosome purification yield varied and almost conflicting results with regards to which protocol is the most promising.

Taking ultracentrifugation as an example, huge differences in efficiency of exosome recovery are reported across research groups [70]—[72] when compared to commercial kits and affinity- base purification methods. In one such study, lab scale commercial kits processing human serum samples up to a volume of 5 mL isolated an fold higher yield of exosomes than ultracentrifugation [51].

The method often cited is based on antibody-conjugated magnetic beads, which can be used to pull out exosome populations from crude material. A study comparing exosome recovery from human colon cancer cell line LIM [70] revealed that exosomes captured via immuno-affinity were superior in terms of expression levels of known exosomal markers, compared with ultracentrifugation and differential centrifugation. Moreover, the vesicles were much more homogeneous nm diameter compared with those from ultracentrifugation nm and differential centrifugation nm.

This shows powerful potential in terms of product characterization and isolation. In the current format, scaling up becomes increasingly burdensome because mixing, mass transfer and removal of beads via magnetic separation is achieved with limited efficiency at the larger scales and also requires specialist equipment [73]. However, the use of these beads at laboratory scale suggest that they could have potential in large scale processing if the issues surrounding introduction of process impurities are successfully overcome.

As such, further development of chromatographic steps which facilitate the specific capture of exosomes or their subtypes may likely be important. A recent study demonstrated the applicability of chromatographic purification by use of a quaternary amine QA anion exchange column AEx column against sucrose density gradient separation of amniotic fluid derived exosomes [74].

Increased throughput may be possible because higher flow rates can be used; this approach has already been adopted in the virus industry [75]. Tangential flow filtration is a good candidate and concentrated MSC- secreted exosomes up to fold [30]. Further evidence for this shift in technologies is supported by a study where ultrafiltration and liquid chromatography UF-LC steps in this case size exclusion chromatography using Sephacryl columns were tested against differential ultracentrifugation [69].

The results showed significantly higher yields from the UF-LC method relative to differential ultracentrifugation without compromising the proteomic identity of EVs, while also showing that the biophysical properties were preserved. The authors also observed an improved bio-distribution of the EVs when injected into mice: fewer EVs accumulated in the lungs, likely due to the reduction of aggregation and damage to the exosomes during the UF-LC steps compared to ultracentrifugation[69].

However, equally critical, and underpinning these advances, is the capacity to measure and characterize the exosome product better than currently achieved. It will be easier to address the process development and scale up of exosome product if the process is guided by a robust, regulatory accepted definition of what it is. The exosome community has already taken significant steps to provide a broad definition for exosomes and provide criteria for their identification.

The International Society of Extracellular Vesicles ISEV has established a set of criteria for proteomic identification of exosomes with a minimal list of requirements [76], namely, exosomes should i possess transmembrane proteins to provide evidence of a membrane e. TSG, Rab proteins or annexins ; iii be free of protein impurities from intracellular compartments not associated with the plasma membranes or endosomes e.

However, ultimately more detailed characterization must be undertaken to describe exosomes in terms of functional capacity by mechanistically defining the action of key nucleic acid and protein signals on target cells, and by understanding exosome heterogeneity. For example, a larger exosome may contain larger quantities of certain RNAs or proteins, or a smaller exosome may have a higher density of surface markers. Furthermore, assays need to be developed that detect exosomes with higher reliability and accuracy than at present.

This microfluidic approach even offers potential for development of in-line measurement technologies that can monitor exosome production during cell culture as a label-free surrogate measurement of the cells, and using exosome identity as a surrogate for cell identity and state. It might even be possible to isolate exosomes themselves using label- free tools. For example, microfluidic devices have been developed that utilize transmission surface plasmon resonance [59] or acoustic waves [60] to isolate exosomes from other vesicles and cells.

While these tools may not fulfill the requirement of a large scale purification platform, they might offer potential as label-free methods to isolate exosomes that can be subsequently characterized, e. Naturally, if the live cells are being used as a therapy in their own right and the exosomal product is a secondary product, the screening of adventitious agents such as viruses would be a pre-requisite and would lower risks of high titers entering the final product.

Furthermore, if, for example, dedicated cell lines for the production of exosomes for drug delivery or gene editing are created, mimicking recombinant protein and antibody production systems, one may find proof of viral removal is absolutely necessary. At this point, one must scrutinize the current technologies available and find methods where an exosome may be separated from any viruses which may be present. A common method of inactivation is that of exposure to low pH 3 , typically during a chromatographic step: however, this method risks damaging exosomal surface proteins, or, if not strongly bound to the column, eluting the product altogether.

Similarly, other techniques such as ultraviolet UV inactivation, which aim to disrupt the nucleic acid sequences for viral attenuation, could also irreparably damage the exosome product.

This poses a further challenge on the analytical spectrum because even if exosomes could be shown to be up-taken in using in vitro quality control assays due to the lack of damage to surface proteins , any damage to the internal genetic material may cause them to perform with limited or null activity biologically which reinforces the need for suitable potency assays.

With several prominent pre- clinical studies showing potent effects of exosomes, and some early clinical data are emerging, it is timely to address the bioprocessing challenges that underpin manufacture of exosomes and other EVs. While phenomenal progress has been made in understanding the biological properties of exosome cargo, research must also focus on challenges related to achieving regulatory approval and potential translational into the clinical setting.

There are still many unanswered questions and hurdles to overcome, see Outstanding Questions and Box 1 , in order to deliver exosomes as a new putative therapeutic tools for healthcare.

These challenges will come in many forms: from scheduling and batch reproducibility, to process robustness and economic feasibility, along with thoroughly defining meaningful critical quality attributes for the product itself. It is vital that these issues are investigated fully in parallel with clinical validation studies in order to contemplate delivering exosomes to the clinic and to the patients who might benefit.

Exosome biogenesis left begins when multi-vesicular bodies MVBs 1 bud inwards to form intraluminal vesicles ILVs that are loaded with genetic material and proteins 2. Next, MVBs fuse either with lysosomes 3A which results in proteolytic degradation of exosomal contents, or with the plasma membrane 3B , resulting in the release of ILVs, now referred to as exosomes, into the extracellular environment.

Non- exosomal vesicles bud directly from the cell membrane 4. Exosomes are typically in the size range of nm and their structure right is complex. Tetraspanins e. CD81, CD63, CD9 and other transmembrane proteins such as adhesion receptors are present at the surface, while internally, the cargo comprises an array of proteins cytosolic, cytoskeletal, growth factors and miRNAs that convey specific functional cues.

Diagrammatic representation of exosome function after in vivo stem cell transplantation. Implanted stem cells synthesize exosomes that convey functional characteristics of parental cells a. Exosomes are then released by stem cells into the surrounding environment b and induce functional responses in adjacent resident tissue cells c that can modify the behavior of target cells, even resulting in sustained regenerative responses d after the stem cell has perished or exited the injury site.

Schematic showing the current laboratory scale methods used for upstream processing of stem cells top. Cells are retrieved from the patient or from a working cell bank WCB and expanded predominantly using a T-flask platform. This leads to a number of significant pitfalls associated with current technologies. Development of new upstream processing is necessary bottom in order to scale up the production of large quantities of cells from the WCB and therefore large quantities of exosome product that can be made in a closed bioreactor system and with greater process control.

Diagrammatic representation of the current laboratory scale methods used for downstream processing of stem cell-derived exosomes top. Crude conditioned media concentration is achieved using filtration and then ultracentrifugation methods are used to isolate exosomes on the basis of size and density.

Collino, M. Deregibus, S. Bruno, L. Sterpone, G. Aghemo, L. Viltono, C. Tetta, and G. Heijnen, A. Schiel, R. Fijnheer, H. Geuze, and J. Raiborg and H. Trajkovic, C. Hsu, S. Chiantia, L. Rajendran, D. Wenzel, F. Wieland, P. Schwille, B. V Vlassov, S. Magdaleno, R. Setterquist, and R. Acta, vol. Schageman, E.

Zeringer, M. Li, T. Barta, K. Lea, J. Gu, S. Setterquist, and A. Conde-Vancells, E. Suarez-Rodriguez, N. Embade, D. Gil, R. Matthiesen, M. Valle, F. Lu, J. Mato, and J. Yu, S. Harris, and A. Koga, K. Matsumoto, T. Akiyoshi, M. Kubo, N. Yamanaka, K. Tasaki, H. Nakashima, M. Nakamura, S.

Kuroki, M. Tanaka, and M. Nadkarni and Hofmann proposed a research model to identify underlying motivations in social media usage. Their results suggest two primary psychological needs as self-presentation and belonging.

Similarly, affiliation and dominance were significantly associated psychological needs with both individualism and internet addiction in the present study. Satisfying psychological needs in a healthy manner contributes to overall well-being, happiness e. Vansteenkiste et al. Deci and Ryan, Otherwise, pathological complications such as depression or loneliness e. Wei et al. Wan and Chiou, , or internet addiction e. Chou et al. Each of the suggested strategies targets the satisfaction of a specific psychological need.

Results also underline the importance of collaboration among the student, family, and counselor in dealing with the internet-related problems. Experts are virtually in complete agreement for setting limits and monitoring students while they are on the internet as a preventive way of avoiding internet addiction.

These findings indicate the possibility of using schema therapy in the prevention of internet addiction e. Experts also suggested reality check and taking responsibility to prevent internet addiction and to satisfy autonomy need.

Such suggestions may be most appropriately addressed by choice theory Glasser, , , Experts suggest setting attainable goals, becoming competent in effective time management, and self-monitoring skills.

Such suggestions could be effectively addressed in goal achievement theory Murayama and Elliot, and metacognitive learning strategies such as planning, monitoring, and evaluating Wolters, ; Zimmerman, , In sum, the results of the qualitative findings indicate that schema therapy can be employed with internet addiction problems.

In addition, choice theory and goal achievement theory may provide helpful guidelines with psychological needs. Quantitative results indicate that individualism has a major role in shaping psychological needs, which, in turn, significantly affect all internet addiction components. Therefore, it is important to satisfy psychological Individualism needs in healthier ways. Nonetheless, it carries several limitations. First, sample size restrictions did not permit the analysis of possible gender differences.

Therefore, future research should investigate gender differences in the mediation role of psychological needs in the context of individualism and internet addiction. Comparable studies should be conducted in different cultures to increase the external validity of the current findings. Third, qualitative analyses have been conducted neither to support quantitative data nor to better explain or understand quantitative findings.

Instead, qualitative part of the study was conducted with expert therapists to search for socially healthier ways to satisfy psychological needs in order to guard against internet addiction.

However, testing the effectiveness and efficiency of these advises was beyond the scope of the current study. Therefore, we suggest that future research focuses on testing the effectiveness and efficiency of advises extracted in the present study.

Fourth, espoused culture is not the only determinant of internet addiction nor is psychological needs the only mediator without other circumstantial factors; however, we made a conscious choice, based on relevant literature, to use a single exogenous factor, individualism and a single mediator, psychological needs in our model. Many other situational or dispositional factors e. Therefore, our suggestion is that the current model is supported, not proven.

Future studies should replicate the model to increase its external validity. Finally, there are few methodological limitations such as using convenience sampling and using cross-sectional data.

References Agag, G. Beard, K. Bentler, P. Bollen, K. Caplan, S. Carli, V. Chan, A. Chen, L. Chen, S. Cheng, C. Chirkov, V. Chou, C. Davis, R. Deci, E. Dizen, M. Dhir, A. A, pp. Elbeltagi, I. Eysenck, H. Foster, D. Frost, D. Gambrel, P. Glasser, W. Glenn, S. Greitemeyer, T. Hahn, E. Heckert, T. Hofstede, G. Hollander, E. Hooker, J. Hoyle, R. Huang, C. Hui, C. Jiang, Q. Kardefelt-Winther, D.

Kesici, S. Kim, Y. Ko, C. Kraut, R. Lee, Y. Li, D. Liang, L. Lin, H. Lin, S. Lopez, S. McDonald, R. Mafe, C. Marsh, H. Maslow, A. Masuda, A. Meerkerk, G. Merriam, S. Min, S. Munro, D. Murayama, K. Murillo, D. Murray, H. Nadkarni, A. Nath, R. Nie, J. Ogihara, Y.

Podsakoff, P. Qiaolei, J. Ryan, R. Eds , Handbook of Personality: Theory and Research, 3rd ed. Sanchez-Franco, M.

 
 

 

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Experts suggest setting attainable goals, becoming competent in effective time management, and self-monitoring skills. Such suggestions could be effectively addressed in goal achievement theory Murayama and Elliot, and metacognitive learning strategies such as planning, monitoring, and evaluating Wolters, ; Zimmerman, , In sum, the results of the qualitative findings indicate that schema therapy can be employed with internet addiction problems.

In addition, choice theory and goal achievement theory may provide helpful guidelines with psychological needs. Quantitative results indicate that individualism has a major role in shaping psychological needs, which, in turn, significantly affect all internet addiction components. Therefore, it is important to satisfy psychological Individualism needs in healthier ways.

Nonetheless, it carries several limitations. First, sample size restrictions did not permit the analysis of possible gender differences. Therefore, future research should investigate gender differences in the mediation role of psychological needs in the context of individualism and internet addiction.

Comparable studies should be conducted in different cultures to increase the external validity of the current findings.

Third, qualitative analyses have been conducted neither to support quantitative data nor to better explain or understand quantitative findings. Instead, qualitative part of the study was conducted with expert therapists to search for socially healthier ways to satisfy psychological needs in order to guard against internet addiction.

However, testing the effectiveness and efficiency of these advises was beyond the scope of the current study. Therefore, we suggest that future research focuses on testing the effectiveness and efficiency of advises extracted in the present study. Fourth, espoused culture is not the only determinant of internet addiction nor is psychological needs the only mediator without other circumstantial factors; however, we made a conscious choice, based on relevant literature, to use a single exogenous factor, individualism and a single mediator, psychological needs in our model.

Many other situational or dispositional factors e. Therefore, our suggestion is that the current model is supported, not proven. Future studies should replicate the model to increase its external validity. Finally, there are few methodological limitations such as using convenience sampling and using cross-sectional data. References Agag, G. Beard, K. Bentler, P. Bollen, K. Caplan, S. Carli, V. Chan, A. Chen, L. Chen, S. Cheng, C. Chirkov, V. Chou, C. Davis, R. Deci, E. Dizen, M. Dhir, A. A, pp.

Elbeltagi, I. Eysenck, H. Foster, D. Frost, D. Gambrel, P. Glasser, W. Glenn, S. Greitemeyer, T. Hahn, E. Heckert, T. Hofstede, G. Hollander, E. Hooker, J. Hoyle, R. Huang, C. Hui, C. Jiang, Q. Kardefelt-Winther, D. Kesici, S. Kim, Y. Ko, C. Kraut, R. Lee, Y. Li, D. Liang, L. Lin, H. Lin, S. Lopez, S. McDonald, R. Mafe, C. Marsh, H. Maslow, A. Masuda, A. Meerkerk, G. Merriam, S. Min, S. Munro, D. Murayama, K. Murillo, D. Murray, H. Nadkarni, A. Nath, R. Nie, J. Ogihara, Y. Podsakoff, P.

Qiaolei, J. Ryan, R. Eds , Handbook of Personality: Theory and Research, 3rd ed. Sanchez-Franco, M. Schwartz, S. Sheldon, K. Sheldon, P. Shweder, R. Singelis, T. Sobel, M. Spence, J. Stavropoulos, V. Strauss, A. Tam, C. Triandis, H. Truzoli, R. Vansteenkiste, M. Vega, W. Wan, C. Wasti, A. Waterman, A.

Wei, M. Wolters, C. Wong, T. Yang, S. Young, J. Young, K. Yu, C. Zhao, F. Zhou, Y. Zimmerman, B. Further reading Kim, Y. The Appendix follows overleaf. I find myself organizing and directing the Sample items activities of others 0. Disadvantages of being an individualist in an individualistic culture: Idiocentrism, emotional competence, stress, and mental health.

The global village: online cross-cultural communication and HRM. Culture and concepts of power. Jung, J. Journal for the Education of the Gifted, 36, Georgiou, St. Authoritarian parenting, power distance and bullying propensity.

Journal of Cross-Cultural Psychology Individualism and good works: Cultural variation in giving and volunteering across the United States. Psychological Bulletin Rethinking individualism and collectivism: Evaluation of theoretical assumptions and meta-analyses.

Promoting autonomy by promoting groupwork in Japanese university EFL classes. Cross-Cultural Organizational Behavior. Individualism vs collectivism scale. The effect of personality traits on private brand consumer tendencies: A cross-cultural study of Mediterranean countries.

Violence related attitudes, horizontal individualism and collectivism in young mexicans. Gelfand et al. European Journal of Personality Three components of individualism. The Leadership Quarterly Research on leadership in a cross-cultural context: Making progress, and raising new questions. International Journal of Market Research The myth of China as a single market: The influence of personal value differences on buying decisions. The impact of Arab cultural values on online social networking: The case of Facebook Mobile crowdsourcing technology acceptance in the crises mnagement View project.

The Hofstede model Applications to global branding and advertising strategy hofstedand research. Dhodapkar, S. Rusakiewicz, A. Eggermont, J. Pitt, L. Nassar, M. El-ansary, D. Sabry, M. Mostafa, T. Fayad, E. Kotb, M. Temraz, A. Essa, and H. Kordelas, V. Rebmann, a-K. Radtke, J. Ruesing, T. Doeppner, M. Epple, P. Beelen, and B. Kirouac and P. Ahrlund-Richter, M. De Luca, D. Marshak, M. Munsie, A. Veiga, and M.

Bergman and G. Lau, U. Ogbogu, B. Taylor, T. Stafinski, D. Menon, and T. Isasi, V. Rahimzadeh, and K. Genomics, vol. Li, H. Atkins, and T. Vishnubhatla, R. Corteling, L. Stevanato, C. Hicks, and J. Gardiner, D. Di Vizio, S. Sahoo, C. Thery, K. Witwer, M. Wauben, and A. Vesicles, vol. Chen, X. Chen, A. Boon, H. Choo, S. Reuveny, S. Kah, and W.

Fernandes, T. Fernandes, M. Diogo, C. Lobato, D. Henrique, and J. Gerlach, D. Ph, Y. Lin, D. Ph, C. Brayfield, D. Ph, D. Minteer, H. Li, J. Rubin, K. Marra, and D. Part C Methods, vol. Carswell and E. Brindley, K. Moorthy, J. Lee, C. Mason, H. Kim, and I.

Tissue Eng. Bollini, C. Gentili, R. Tasso, and R. Crescitelli, C. Szabo, A. Kittel, M. Eldh, I. Dianzani, E. Buzas, and J. Boussac, P. Ricciardi-Castagnoli, G. Raposo, J. Garin, and S. Wen, Y. Chang, L. Lin, and P. Mitchell, J. Court, M. Mason, Z. Tabi, and A. Methods, vol. Jeon, M. Lee, and Y. Shelke, C. Lasser, Y. Gho, and J. Lee, H. Johansson, I.

Mager, P. Vader, J. Nordin, O. Wiklander, J. Wood, and S. Schnitzler, S. Rigby, M. Aysola, and J. Li, M. Kaslan, S. Lee, J.

Yao, and Z. Clayton, S. Amigorena, and G. Reimer, R. Baker, R. VanFrank, T. Newlin, G. Cline, and N. Cvjetkovic, J.

Witwer, E. Bemis, A. Bora, C. Piper, S. Sivaraman, J. Skog, C. Wauben, and F. Linares, S. Tan, C. Gounou, N. Arraud, and A. GOOL, and R. October , pp. Welton, J. Webber, and L. Tan, Y. Yin, T. Lai, R. Yeo, B. Zhang, A. Choo, and S. Nordin, Y. Lee, P. Vader, I. Johansson, W. Heusermann, O. Seow, J. Bultema, J. Gilthorpe, T. Davies, P. Fairchild, S. Meisner-kober, J. Smith, M. Tauro, D. Greening, R. Ji, S. Mathivanan, A. Scott, and R. Webber and A. Helwa, J.

Cai, M. Drewry, A. Zimmerman, B. Dinkins, M. Khaled, M. Seremwe, W. Dismuke, E. Bieberich, W. Stamer, M. Hamrick, and Y. Yavuz, A. Prakash, J. Mayo, and V. Kosanovic, B. Milutinovic, S. Goc, N. Mitic, and M. Burden, J. Jin, A. Podgornik, and D. Life Sci. Lotvall, A. Hill, F. Hochberg, E. Buzas, D. Di Vizio, C. Gardiner, Y. Gho, I. Mathivanan, P. Quesenberry, S. Sahoo, H. Tahara, M. Wauben, K. Kowal, G. Arras, M.

Colombo, M. Jouve, J. Paul, B. Primdal-bengtson, F. Dingli, D. Tkach, and C. Reyes, S. Josefa, J. Carrascosa, C. April, pp. Sofer, D. Lister, and J. Their specific cargo is reflective of the parent cell, and gives rise to their therapeutic effects. However, to achieve potential as therapeutics scalable manufacturing processes are needed, both upstream and downstream.

Current bioreactor technology is designed for suspension-adapted cells that are used to make antibodies or recombinant proteins. Mass Spectrometry Reviews Mass spectrometry of extracellular vesicles. Proteome science New insights in the composition of extracellular vesicles from pancreatic cancer cells: implications for biomarkers and functions.

Archives of Biochemistry and Biophysics Extracellular vesicles: Specialized bone messengers. Journal of extracellular vesicles Comparative analysis of discrete exosome fractions obtained by differential centrifugation. Nature Reviews Urology The emerging role of extracellular vesicles as biomarkers for urogenital cancers.

Journal of Extracellular Vesicles The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling.

Journal of Extracellular Vesicles Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. BMC clinical pathology Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology. Translational Cancer Research Exosomes and other extracellular vesicles-mediated microRNA delivery for cancer therapy.

Purified horse milk exosomes contain an unpredictable small number of major proteins. Extracellular Vesicles in Cardiovascular Theranostics. Scientific Reports Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells.

Electrophoresis Recent advances and challenges in the recovery and purification of cellular exosomes. The absorption properties of NWs when they are vertically standing are determined by the waveguide modes [ 82 ].

InP NW arrays, which are vertically aligned and grown on a semi-infinite SiO 2 substrate are schematically shown in Figure 5 with either squarely or hexagonal arrangement. Repeatable unit cells in Figure 6a and b insets show respective characterization dimensions for each arrangement. Such morphology and topology of the NW arrays are in accord with the majority of the InP NW-based photovoltaic cell structures. Periodicity P is the core to core spacing of a pair of adjacent NWs that has an analogous value for squarely arranged NWs, whereas fully different values for hexagonal NW clusters.

NWs are more efficient in light absorption compared to thin-film materials of an equivalent volume. Krogstrup et al. On other hand, when the NW is lying horizontally, the absorption properties are determined by leaky-mode resonances, which provide a chance to engineer the light absorption in NWs by controlling their physical dimensions [ 85 ]. Once the resonant modes are supported by the NWs leaky, the overlap between the incident electromagnetic attraction field and the guided mode profile is maximized, facilitating enough coupling with incident light.

Due to their outstanding advantages, NW arrays have advanced light trapping ability and hence strongly enhanced optical absorption in comparison with the thin-film [ 86 ]. This can significantly enhance the broadband light absorption over a good range of incident angles, especially the near and below bandgap absorption [ 81 , 87 ].

With the same thickness as thin-film layers, the NWs short-circuit current can reach high results [ 88 ]. Nanowire diameter and separation are typically on the order of the wavelength of sunlight, where interference effects are dominant, therefore, the reflectance, absorptance, and transmittance of nanowire arrays must be determined using wave optics [ 89 ]. Long Wen et al. The absorptance of a 2. In the long-wavelength regime, the absorption spectra show a significant increase when increasing diameter from 60 to nm.

The electromagnetic field can be coupled efficiently into the NWs at resonances, due to the large refractive index contrast between the NWs and surrounding air. For small diameter GaAs NW arrays, with fewer supporting modes, most of the incident light cannot be guided into the NWs. Figure 7b shows plots of the vertical cross-section of the photogeneration profiles.

Only a little fraction of the incident wave is transmitted onto the substrate, this will be explained by the short absorption length of GaAs at this wavelength. At nm and above, for a NW, the photogeneration rates are focused on several lobes that form along the NWs for a NW array with nm diameter, indicating strong guided modes confined within the NWs.

Clearly, the nm diameter NW array induces a much larger optical concentration than the 60 nm diameter one. From both Figures 6 and 7 one can easily understand the effect of NW diameter on photon energy harvesting. Photocurrent density is often further bettered by adding nanowires length L. Due to the proliferation of NW length, the donation from the nanowire to all photocurrent rises, while the GaAs substrate donation similarly decreases.

The uttermost photocurrent of Theoretical contributions from a GaAs nanowire array and the GaAs substrate to the total photocurrent density in a PV device versus nanowire length obtained at a nanowire diameter of nm and period of nm [ 90 ]. Also, the NW solar cells cast smaller photons than the bulk cell at the identical occasion, which allows for a more open-circuit voltage. They have predicted the unborn capabilities in affecting both the emission and absorption characteristics of the NW assemblages, for instance, by 1 varying NWs shape, 2 varying the period of NWs, 3 sheeting the NWs with a nonabsorbing dielectric shell, 4 fitting a dielectric material between the NWs, and 5 by introducing optical antireflection layers on top of the NW.

Such improvement of the NW array could conceivably further accelerate its effectiveness limit. Based on the axis of charge carrier separation, an axial and a radial junction device are the two broadly classifying NW solar cells.

The charge carrier separation happens along the length of the nanowire and the radial axis, in axial junction, and radial junction solar cells, respectively. Figure 9a and b display sunlight absorption and charge carrier separation in both axial and radial junctions NW solar cells correspondingly. In a solar cell, the minimum length needed to attain ample absorption is characterized by absorption depth.

The absorption depth explains how deeply light penetrates the NW semiconductor or every type of solar cell device before being absorbed. At the same time, diffusion length describes the maximum length that the minority charge carrier can travel before making recombination non-radiatively [ 91 ].

For solar cells, in order for them to efficiently operate, the diffusion length should be higher than the absorption depth, as schematically shown in Figure 9. Radial junction is preferable for the fabrication of large-efficiency devices by connecting the light absorption and charge carrier separation axes. In a radial junction PV cell, sunlight absorption is along the main axis of the NW, while the charge carrier separation takes place within the radial direction, which is in nm-scale thickness.

In other words, to realize the optimum performance of the NW photovoltaic cell in a radial junction photovoltaic cell, both charge carrier separation, and light absorption can separately be optimized.

Nanowires solar cells schematic representation of a an axial p-n junction, and b a radial p-n junction. Yao et al. They have also synthesized GaAs NWs solar cells with an axial p-i-n junction by selective area growth method, which is compatible with MOCVD technique, and they observed that low filling ratio NWs are highly absorbed. They have also studied the effect of the diameter and revealed that thicker NWs are favorable because of the high surface recombination velocity on the bare GaAs NW surface.

They identified that by decreasing junction depth to around nm and maintaining diameter at nm, able to achieve efficiencies as high as 7. Their results demonstrated that GaAs NWs are good candidates for high-efficiency and low-cost solar energy conversion and open up great opportunities for the next generation photovoltaic based on multi-junction devices composed of lattice-mismatched material systems.

For solar cells, one of the key needs is to realize efficiency that keeping a huge optical thickness to facilitate high light absorption and a tiny low electrical thickness to facilitate high photogenerated carrier assortment at the contacts. The gathering of high photogenerated carriers depends powerfully on the diffusion length of minority carriers, which decline quickly with the rise in density of defect [ 22 ].

Generated carriers are going to be wasted when they are quite one diffusion length far away from the space charge region [ 92 ]. The diffusion length, L d , of electrons or holes in a semiconductor is defined by the mean distance the relevant charge moves within the semiconductor.

Diffusion is the movement of charge carriers directed by a concentration gradient. When the cell is not operational at open-circuit voltage, that is, the charge is extracted, and then the lifespan can clearly be less due to the removal of the charge extracted. This is no longer an intrinsic property of the absorbing semiconductor itself, however, depends on the interfaces that exist between the semiconductor and charge extraction phases. The lifespan of charge refers to the minority charge carrier lifespan for semiconductors that are obviously either n-type or p-type.

Differentiation into majority and minority carrier lifetimes is not obvious for an intrinsic semiconductor, such as the intrinsic semiconductor in a p-i-n cell [ 93 ].

In a conventional thin-film device, the gathering path of the generated carriers is parallel to the solar photon traveling path. Thus, thick enough absorption materials are in high demand on the quality of the crystal, in order that the carriers can easily undergo without any substantial recombination.

The morphological anisotropy of nanowires provides the advantage of decoupling the optical and electrical thickness of PV cells by using the co-axial contact structure [ 91 ]. It can absorb sunlight along the entire nanowire, while the generated carriers are frequently separated within the radial direction.

The radial distance that carriers need to travel in the s nm range is generally much lower than, or similar to the minority carrier diffusion length. So far, the orthogonally severed sunshine and carrier separation paths can cause low bulk recombination, and hence high effectiveness. Also, the NWs have a high surface-to-volume ratio, which offers a large junction area that will further enhance the charge separation effectiveness.

The study showed that the influence of adjusting the diffusion length under radial junction may be a smaller amount than in planar junction, that is the utmost efficiency of both radial p-n junction geometry and planar geometry can increase with increasing diffusion length, but the planar geometry increases more [ 94 , 95 ]. The difference in the performance between the planar and radial structures for III—V semiconductors with a high carrier diffusion length is, not as clear as that for Si [ 94 ].

However, NWs have a large surface-to-volume ratio and hence, a large density of surface state [ 93 , 96 ]. All these merits allow using lower-purity, less expensive materials with low minority carrier diffusion lengths to make high-efficiency solar cells.

Consequently, the use of the NW structure can enormously decrease the device cost. Due to these advantages, NWs are promising high-efficiency and less expensive solar cells and have the potential to revolutionize solar power harvesting technology. The distinctive structure and advanced properties of NWs provide additional freedom in constructing novel solar cells with high-efficiency and low-cost.

Tandem solar cell [ 97 ] is one type of design in order to have high efficiencies in solar cells, which is to use multiple semiconductors epitaxially grown on top of each other. Figure 10 shows the system with two different semiconductor materials, where one material is used as top materials and different materials are used as bottom cell materials. In this figure L top , L bot , D top , and D bot illustrate the length of the top cell, length of the bottom cell, the diameter of the top cell, and diameter of the bottom cell, respectively.

It is to absorb high-energy light in a large bandgap top cell in such a tandem solar cell. Compared to the single junction cell, the thermalization loss of the high-energy light is decreased in the top cell. Then, the lower energy light continues to the bottom cell where these energies are absorbed. The bottom cell has a lower bandgap and due to the lower bandgap than in the single-junction cell, more photons are absorbed in the bottom cell.

Consequently, the tandem solar cell can absorb more photons than single-junction cells and also can have reduced thermalization loss. However, in planar cells, the crystal lattice constant should be matched in adjacent subcells to offer high-quality materials [ 97 ].

Due to this lattice mismatch, they cannot grow on Si substrate, which is the second most abundant earth element and cheap. Moreover, the III—V multi-junction cells in the conventional thin-film structure can give high-efficiency but need to use Ge as substrates, which is expensive. The blending of III—V solar cells on Si substrates can greatly reduce the value, which is extremely challenging. Nanowire structures give an obvious advantage for multi-junction solar cells compared with thin-film cells.

NWs have efficient strain relaxation, which permits for the fabrication and combination of dislocation-free and highly lattice-mismatched materials. In another word, III—V nanowire arrays can be grown on top of a Si substrate, giving the prospect of using the Si substrate as the bottom cell. The optimum structure needs the absolute stylish NW cell to have a direct bandgap of near 1.

The optimum structure also requires equal current from each sub-cell, videlicet a current-corresponding condition. This may be realized by conforming the periphery, length, and period of the NW array. Thus, NW solar cells have further degrees of freedom compared with thin-film solar cells, whose current-matching is achieved by conforming to the consistency of the absorbing subcaste in each subcell.

The optimum building needs the absolute stylish NW cell to possess a direct bandgap of closer to 1.

The optimum building also requires equal current from each subcell, namely a current-matching condition. This may be realized by conforming to the length, period, and diameter of the NW array. Thus, NW solar cells have more degrees of freedom compared with thin-film solar cells, whose current-matching is achieved by adjusting the thickness of the absorbing layer. Hu et al.

They obtained the best photocurrent density of Their simulation showed that the current-matching condition plays a crucial role in the overall efficiency of the device. They also have characterized that GaAs NW arrays were grown on lattice-mismatched Si substrates, which are less expensive. They concluded that tandem solar cells supported top GaAs nanowire array solar cells grown on bottom planar Si solar cells, open up great opportunities for high-efficiency and low-cost multi-junction solar cells.

Axial and radial tandem solar cells [ , , ] are another form of solar cell designing. In axial tandem solar cells, because the photogeneration events happen most often in the middle of NWs, they cannot intrinsically block the generated carriers from reaching the surface and recombining like the radial junctions. Due to a similar reason, the radial tandem solar cell faces a challenge of inefficient absorption for the cell junctions away from the core of NWs.

Thus, a composite structure that combines the advantages of the axial and radial structures would provide much higher efficiency compared with homogeneous ones [ ]. Furthermore, NWs have a little cross-section, which allows them to accommodate big strains axially and laterally and this may greatly facilitate the blending of materials with large lattice mismatch, providing more freedom within the structure design compared with thin-film devices [ ].

An axial NW heterojunction structure with lattice mismatch can be created from the results that the axial junction will distribute the strain across the interface, which will relax the straining step by step and elastically. Regardless of the length, there exists a critical diameter below which no interface dislocation is often introduced. For example, Ercolani et al. They have also observed that zincblende structure InSb is often grown without any crystal defects.

With the same concept, the nanowire core has advantages with regard to lattice-mismatch strain in that it can share the nearest mismatch strain, which results in a drastically reduced strain within the shell [ ]. NW core-shell structure can thus accommodate larger lattice mismatch compared with thin-film structures [ ].

Nazarenko et al. They demonstrated that a shell thickness around nm defect-free GaAs grown on In 0. Their TEM characterization showed an outstanding crystal quality in the entire pillar without defects. Wang et al. In order to evaluate the performance of this NW, they have used a coupled 3D optoelectronic simulation and their simulation results revealed a high conversion efficiency of After an outstanding current matching, a promising efficiency of Figure 12b illustrates vertically aligned NW arrays of axially connected core-shell structures.

The unique structure of NW p-n junctions enables substantial light absorption along the NW length and efficient carrier separation and collection within the radial direction. Heurlin et al. By applying in situ etching for total control over axial and radial growth they connected two photocurrents having p-n junctions in series by a tunnel junction.

They also believed that this provides the best way toward realizing high-efficiency multi-junction solar cells that can be fabricated on a large area and low-cost Si substrates.

Multi-terminal NW solar cell is also another promising design of nanowires. Introducing multiple bandgap concepts into NW solar cell designs has high promise for maximum solar conversion efficiency [ ]. Dorodnyy et al. These authors used Al 0. However, the main challenge would be the matter of growing different NW groups with different lengths required for device fabrication.

The mixing of inorganic NW and organic will give the opportunity to have hybrid solar cells and is also another design of the solar cells to offer high-efficiency materials [ , , , ].

These two materials have their own advantages. Inorganic materials commonly possess high carrier mobility and affinity, whereas organic polymers commonly possess low carrier mobility and a short lifetime, which leads to low device efficiency. However, organic polymers are low in cost; as a result, researchers attempt to mix together the advantages of the two material systems. NWs can also be fabricated and designed as branch cells.

Branched NWs solar cells [ , , ] can also be referred to as nanotrees or nanoforests. These nanowires have a tunable 3D morphology, homo or heterogeneous junction, and interface electronic alignment represent a unique system for applications in energy conversion and storage devices. Lundgren et al. There has been great progress in fabricating branched NWs [ ].

Lightweight and flexible solar cells are necessarily important for designing high-efficiency solar cells [ ]. Lightweight and flexibility are two of the desired properties, which can substantially reduce the facility weight, minimize the transportation cost, and cause the assumption of smart solar cells, such as integrating flexible cells into clothing.

NWs provide unique merits in realizing these advanced functions, as they are going to be buried into polymers and then easily peeled away from the substrates. Han et al. All the above discussed novel designs are very important for providing highly promising III—V NWs to greatly reduce the worth and boost the efficiency of solar cells, which may revolutionize the current solar cell technologies. Values for each parameter and their growth mechanisms are also summarized.

Therefore, researchers around the world are trying to increase the efficiency of these materials by using novel designs, improving growth mechanisms, and device fabrication methods.

An efficiency of Power conversion efficiency was measured at 1 Sun, AM1. Afterward, an efficiency of Then, an efficiency of In order to convert solar energy into electrical energy, harvesting solar energy is required and solar photovoltaic is the most promising device for this purpose. This is due to low energy density, low efficiency, and relatively high-cost materials compared to other types of energy technologies. Therefore, novel materials that can enormously harvest sunlight are important and they are the current issues attracting research interest.

Due to its unique properties from bulk materials, III—V NWs can be used as high-performance solar cells because of their attractive advantages, such as unique optical and electrical properties, direct band, and fewer solar light reflections. In constructing novel solar cells with high-efficiency and low-cost, the distinctive structure and advanced properties of NWs provide more freedom.

By controlling the III—V NW morphology and its geometry with optimum diameter, period, and length it is possible to get high-efficiency solar cell materials.

Thus, one of the best aspects of III—V NWs commercialization with high power conversion efficiency may be achieved by designing it in a way that it can absorb solar light enormously with reduction of materials used and low-cost substrates.

According to our understanding, all the designs of III—V NWs that are mentioned in this review are beneficial for future commercialization; however, it is good to identify the one that is more attractive than the others by conducting research on each design.

All types of design have their own advantages in case of reducing materials used for the fabrications of solar cells and cost reductions. So far, it is good if this area will be researched more, especially on the architecture of III—V NWs due to its infinite advantages. Despite the challenges of achieving high efficiency in these NWs, they are the hope of the next-generation solar cells due to their flexibility for designing it even in a multi-junction of different NWs, which can absorb the different wavelengths of solar light for harvesting huge solar light.

Furthermore, to advance III—V NW-based solar cells toward possible commercialization the power conversion efficiency should be increased, for which the tandem architecture is highly interesting by growing on Si substrate, which is cost-effective. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Impact of this chapter. Abstract Nanowires NWs are 1D nanostructures with unique and wonderful optical and electrical properties.

Keywords III—V nanowires nanowire design nanowire synthesis photovoltaic solar cells. Table 1. Conflicts of interest There is no conflict of interest. References 1. Socio-economic and environmental impacts of rural electrification with solar photovoltaic systems: Evidence from southern Ethiopia.

Energy for Sustainable Development. DOI: Energy demand. Elsevier; Edenhofer O et al. Renewable energy sources and climate change mitigation: special report of the Intergovernmental Panel on Climate Change.

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