Silicon Carbide (SiC) is a highly versatile semiconductor material that has long been used in harsh applications such as space, corrosive and high-temperature environments and, more recently, the human body. The impressive and highly advantageous materials properties of SiC have shown that this material is ideally suited for medical applications due to its proven bio- and hemocompatibility. Indeed, SiC appears to be quite unique for use in the human brain whereby implants made using SiC coatings have demonstrated vastly improved performance with virtually no human body immune response which plagues Silicon technology. After over two decades of focused research and development SiC is now ready for use in the healthcare sector and this paper provides an up to date assessment of SiC devices for long-term human use. First the plethora of applications that SiC is uniquely positioned for in human healthcare is reviewed so that healthcare professionals will be fully aware of the significant opportunities now possible with the rapid development of this technology. Next progress in two areas will be presented: Neural implants and deep-tissue cancer therapy using SiC nanotechnology.

Newly developed microfluidic devices (“Mother Machines”) have improved data gathering for the study of aging in unicellular models, and thereby the understanding of this process. Each device has different features that cause them to have certain advantages or disadvantages. At the University of the Andes a new microfluidic device was developed that uses the Slipstreaming effect to trap the cells. This has the advantage of not using mechanical pressure to trap the cells, but as it starts with a mixed age population it does not guarantee that the cells studied are virgin.

One of the basic outputs in these studies is the aging curve, which shows how the fraction of viable cells varies with respect to time. From this it can be deduced how fast or slow the population ages. For devices where it is not possible to work with virgin cells the age distribution is assumed, but changes in this distribution could affect the analysis of the data.

Therefore, the present work seeks to carry out a series of simulations to find the different age distributions that could be present and determine the corresponding changes in the aging curve. We propose two population growth models, synchronous and asynchronous. For each model we will start with the possible age distributions and determine the various curves that can be obtained and then compare these computational results with the experimental data to propose a better interpretation of the data obtained from Mother Machine devices.

Microswimmers are microscopic objects that can move and perform tasks in liquid environments. Although only two decades have passed since their emergence,¹ microswimmers have already attracted significant attention in the scientific world because of their many valuable potential applications. Among these, biomedical applications seem particularly promising, and many interesting studies have been performed already in vitro or even in vivo.² However, no microswimmers have so far been approved for clinical use, which is why ongoing research is often focused on clinical translation or relevant related issues such as biocompatibility.

Different propulsion and control modalities are employed for microswimmers, including biohybrid, optical, magnetic, chemical, thermal or acoustic propulsion. Among these, our group focuses on the use of optical forces generated by manipulating light. For most intents and purposes, light is a biocompatible actuator. However, because of the limited tissue penetration depth, light is only suited for applications in superficial tissues of the human body.³ On the other hand, light-controlled microswimmers can be employed for various laboratory studies relevant for biomedical research, such as cell manipulation, fluid viscosity characterization, or drug delivery. Furthermore, supplementing the use of light with that of e.g. a magnetic actuator can help overcome the challenges encountered in the human body.⁴

Light is a flexible actuator which can be tailored to the desired application. When it comes to light-controlled microswimmers, one option is to use focused near-infrared laser beams for optical trapping. This enables extremely precise manipulation of the microswimmers with six degrees of freedom. Another option is to use visible light to induce shape changes in light-responsive polymers in a controlled manner. Both options are interesting for biomedical applications and have characteristic advantages and challenges.⁵

Designing and fabricating light-controlled microswimmers currently needs tailoring to specific applications, which often requires interdisciplinary teams of highly-trained researchers.⁶ Ultimately, gathering sufficient knowledge and overcoming the existing challenges in the field should enable the development of a toolbox of light-controlled microswimmers readily available for various biomedical studies.

References

1. Ozin G.A., Manners I., Fournier-Bidoz S. & Arsenault A. Dream Nanomachines, Adv. Mater. 2005, 17, 3011.

2. Bunea A.I. & Taboryski, R. Recent Advances in Microswimmers for Biomedical Applications, Micromachines 2020, 11, 1048.

3. Bunea A.I. & Glückstad J. Strategies for Optical Trapping in Biological Samples: Aiming at Microrobotic Surgeons, Laser Photon. Rev. 2019, 13, 1800227.

4. Sitti M & Wiersma D.S., Pros and Cons: Magnetic versus Optical Microrobots. Adv. Mater. 2020, 32, 1906766.

5. Bunea A.I., Martella D., Nocentini S., Parmeggiani C., Taboryski R. & Wiersma D.S. Light-Powered Microrobots: Challenges and Opportunities for Hard and Soft Responsive Microswimmers. Adv. Intell. Syst. 2021, DOI: 10.1002/aisy.202000256

6. Nocentini S., Parmeggiani C., Martella D. & Wiersma D.S. Optically Driven Soft Micro Robotics. Adv. Optical Mater. 2018, 6, 1800207.

Acknowledgements

Ada-Ioana Bunea acknowledges financial support from Villum Fonden (grants number 00022918 and 34424).

Several marine bacteria of the Roseobacter group can inhibit other microorganisms and are especially antagonistic when growing in biofilms. This aptitude to naturally compete with other bacteria can reduce the need for antibiotics in large scale aquaculture units, providing that their culture can be promoted and controlled. Micro-patterned surfaces may facilitate and promote the biofilm formation of species from the Roseobacter group, due to the increased contact between the cells and the surface material. Our research goal is to fabricate biofilm optimal micro patterned surfaces and investigate relevant length scales for surface topographies as well as surface chemistry, which can promote growth and biofilm formation of the Roseobacter group bacteria.

In a preliminary study, silicon surfaces comprising arrays of pillars and pits with different periodicities, diameters and depths were produced by UV lithography and deep reactive ion etching (DRIE) on single-side polished silicon wafers. The resulting surface microscale topologies were characterized using optical profilometry and scanning electron microscopy (SEM). Screening of the bacterial biofilm on the patterned surfaces was performed using green fluorescent staining (SYBR green I) and confocal laser scanning microscopy (CLSM). Different series of experiments were conducted by changing several parameters such as; growth time, shear stress corresponding to particular revolution per minute (rpm) and growth media. Preliminary results indicate that there is a correlation between the surface morphology, and the spatial organization of the bacterial biofilm.

Our results indicate that further investigation leading to optimization of surface topology and surface chemistry will allow us to microfabricate polymer material surfaces where biofilm colonization is enhanced. Such surfaces will enable the introduction of beneficial bacteria in a variety of industrial processes including aquaculture.

Phytopathological adversities are often attributable to human activities (as a consequence of the globalization of trade or tourism mass, changes in common agricultural practices and climate change), adding food losses due to pathogens such as fungi, bacteria, viruses etc.

For this, we are developing a lab-on-chip as a diagnostic approach to phytopathological problems caused by infectious agents capable of spreading in agro-ecosystems, such as the Xylella fastidiosa epidemic in Puglia (Chiriacò et al., 2018) or other bacteriosis and virosis such as Grapevine leafroll-associated virus 3 (GLRaV-3).

In particular, grapevine leafroll disease (GLD) is one of the most important grapevine viral diseases, affecting grapevines worldwide. Several viruses from the family Closteroviridae are associated with it and Grapevine leafroll-associated virus 3(GLRaV-3) is considered as the most important causative agent. Symptoms of GLD can vary greatly with the season, grape cultivar, and climatic conditions and some varieties can be completely symptomless. (Maree et al., 2013). There is no cure for the virus but only preventive actions. In fact, fighting strategy is based exclusively on the use of plant material free from virus, such as the use of certified material. These pathogens can have serious economic and environmental repercussions on two of the major cultivated woody plant of Mediterranean basin, due to the absence of therapeutic techniques and the need of rapid, in-field and low-cost detection methods.

Here we present a lab-on-chip platform coupled with microfluidic module, based on an electrochemical transduction method, able to recognize serial dilutions of Grapevine leafroll-associated virus 3. LOC represents smart and versatile devices due to their miniaturization. They require small sample volumes, allowing a rapid detection of the targets, offering also the opportunity to study biomechanical properties of plants (Nezhad et al., 2013) and other plant cells studies (Nezhad et al., 2014; Julich et al., 2011). In particular, thanks the aid of a microfluidic component, such as polydimethylsiloxane (PDMS), is possible to realize biochemistry conventional laboratories functions such as sample preparation, reaction, separation and detection (McDonald et al, 2000).

This device can show competitive performances with conventional diagnostic methods in terms of reliability, with further advantages of portability, low costs and ease of use, making the difference in real time detection of the pathogens.

The collective cell migration is thought to be a dynamic and interactive behavior of cell cohorts which is essential for diverse physiological developments in living organisms. Recent studies revealed that topographical properties of the environment regulate the migration modes of cell cohorts, such as diffusion versus contraction relaxation transport and the appearance of vortices in larger available space. However, conventional in vitro assays fail to observe the change in cells behavior in response to the structural changes. Here, we have developed a method to fabricate the flexible three-dimensional structures of capillary microtunnels to examine the behavior of vascular endothelial cells (ECs). The microtunnels with altering diameters were formed inside gelatin-gel by spot heating a portion of gelatin by irradiating the µm-sized absorption at the tip of the microneedle with a focused permeable 1064 nm infrared laser. The ECs moved and spread two-dimensionally on the inner surface of capillary microtunnels as monolayer instead of filling the capillary. In contrast to the 3D straight topographical constraint, which exhibited width dependence migration velocity, leading ECs altered its migration velocity accordingly to the change in supply of the cells behind the leading ECs, caused by the progression through the diameter altering structure. Our findings provide insights into the collective migration properties in 3D confinement structures as fluid-like behavior with conservation of cell numbers.

Control over spatial distributions and patterns of individual neurons and their neurites provides an essential tool for studying the meaning of neuronal network patterns. Moreover, the complete direction control of synaptic connections between cells in each neuronal network is also essential to investigate the detailed information on the relationship between the forward and feedback signaling among the cells. Here, we have developed a method for topographical control of the direction of synaptic connections within a living neuronal network using a new type of individual-cell-based on-chip cell-cultivation system with an agarose microfabrication technology. The advantages of this system include the ability to control positions and number of cultured cells as well as flexible control of the direction of elongation of axons and dendrites with stepwise melting of thin agarose layer coated on the cultivation chip with a focused infrared laser beam even during cultivation without any destructive damage on cells. Using this system, we succeeded in forming fully-direction controlled single-cell-based neuronal network from individual Rat hippocampal cells. In this meeting, we discuss the potential damage of heat to cells while stepwise melting of agarose and demonstrate the ability of our on-chip agarose microfabrication method for individual cell-based neural networks.

Electrokinetic displays have become one of the most important display technologies because of their low power consumption, wide viewing angle, and outdoor readability. They are regarded as excellent candidates for electronic paper. This type of display is based on the controlled movement of charged pigment particles in a non-polar liquid under the influence of an electric field. Free charges practically do not exist In nonpolar colloids, due to their low dielectric constant. However, the addition of a surfactant to non-polar colloids often leads to considerable charge induced effects such as increased electrical conductivity and particle stabilization. In this project, we aim to develop a novel electrokinetically driven display. An unprecedented display device is proposed, based on the concerted action of electro-osmosis and electrophoresis in a non-polar fluid. This method could reduce the switching time for displaying information, and extend the applications of electrokinetic displays with video-speed and full color in the future.

Glaucoma is the second leading cause of preventable blindness worldwide following cataract formation. A rise in the intraocular pressure (IOP) is a major risk factor for this disease, and results from an elevated resistance to aqueous humor outflow from the anterior chamber of the eye. Glaucoma drainage devices provide an alternative pathway through which the aqueous humor can effectively exit the eye, thereby lowering the IOP. However, post-operative IOP is unpredictable and current implants are deficient in maintaining IOP at optimal levels. To address this deficiency, we are developing an innovative, non-invasive magnetically actuated glaucoma implant with a hydrodynamic resistance that can be adjusted following surgery. This adjustment is achieved by integrating a magnetically actuated microvalve into the implant, which can open or close fluidic channels using an external magnetic stimulus. This cylindrical-shaped microvalve was fabricated from poly(styrene-block-isobutylene-block-styrene), or ‘SIBS’, containing homogeneously dispersed magnetic microparticles. Micro-rods of this material were fabricated using a combination of femtosecond laser machining with hot embossing. The glaucoma implant is comprised of a drainage tube and a housing element fabricated from two thermally-bonded SIBS layers with the microvalve positioned in between. Microfluidic experiments involving actuating the magnetic rod with a moving external magnet confirmed the valving function. A pressure difference of around 3 mmHg was achieved which is sufficient to overcome hypotony (i.e. too low IOP) – one of the most common post-operative complications following glaucoma surgery.

Photochemistry involves processes in which light, the principal reagent, and photocatalysts, open pathways to diversing photochemical products. Promising results are obtained in reactions where porphyrin complexes coordinated with certain metals are used as catalysts. The most common porphyrin complexes used in various organic reactions were manganese porphyrins. Nowadays, batch reactors used for photochemical reactions are commonly replaced with flow reactors. Microflow reactors are one of the reactors types, whose main characteristic is the micro-dimension of channels (max. diameter of 500 μm). Flow chemistry performed on a microscale bring improvements in many aspects of photochemical reactions, such as efficient and fast phase mixing and heat transfer, precise retention time control, homogeneous use of light irradiation throughout the reaction mixture, process safety, and potentially simple scale-up.

In this research, anionic/cationic manganese(III) porphyrins were used as photocatalysts. The reactions were first performed in a batch reactor where complete conversion of the substrate was observed after 2 h for furostilbene and 16 h for thienostilbene substrate, respectively. As a result, the formation of formyl, epoxy, carbonyl, or hydroxy derivatives were observed. A step forward in process development was made by replacing the batch with microflow reactors. A total of four different tubular microflow reactors were studied and compared with results obtained in a batch reactor based on substrate conversion and reaction time. Reactions were significantly accelerated in microflow reactors where the complete substrate conversion for furostilbene substrate was observed for a residence time of 0.7 min and for thienostilbene substrate for 3.5 min, respectively.