Size based separation of microparticles using a dielectrophoretic activated system

This work describes the separation of polystyrene microparticles suspended in deionized (DI) water according to their dimensions using a dielectrophoretic (DEP) system. The DEP system utilizes curved microelectrodes integrated into a microfluidic system. Microparticles of 1, 6, and 15 μm are applied to the system and their response to the DEP field is studied at different frequencies of 100, 200, and 20 MHz. The microelectrodes act as a DEP barrier for 15 μm particles and retain them at all frequencies whereas the response of 1 and 6 μm particles depend strongly on the applied frequency. At 100 kHz, both particles are trapped by the microelectrodes. However, at 200 kHz, the 1 μm particles are trapped by the microelectrodes while the 6 μm particles are pushed toward the sidewalls. Finally, at 20 MHz, both particles are pushed toward the sidewalls. The experiments show the tunable performance of the system to sort the microparticles of various dimensions in microfluidic systems

Survivin Mutant Protects Differentiated Dopaminergic SK-N-SH Cells Against Oxidative Stress

Oxidative stress is due to an imbalance of antioxidant/pro-oxidant homeostasis and is associated with the progression of several neurological diseases, including Parkinson's and Alzheimer's disease and amyotrophic lateral sclerosis. Furthermore, oxidative stress is responsible for the neuronal loss and dysfunction associated with disease pathogenesis. Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins, but its neuroprotective effects have not been studied. Here, we demonstrate that SurR9-C84A, a survivin mutant, has neuroprotective effects against H2O2-induced neurotoxicity. Our results show that H2O2 toxicity is associated with an increase in cell death, mitochondrial membrane depolarisation, and the expression of cyclin D1 and caspases 9 and 3. In addition, pre-treatment with SurR9-C84A reduces cell death by decreasing both the level of mitochondrial depolarisation and the expression of cyclin D1 and caspases 9 and 3. We further show that SurR9-C84A increases the antioxidant activity of GSH-peroxidase and catalase, and effectively counteracts oxidant activity following exposure to H2O2. These results suggest for the first time that SurR9-C84A is a promising treatment to protect neuronal cells against H2O2-induced neurotoxicity

A Microfluidic System for Studying the Effects of Disturbed Flow on Endothelial Cells

Arterial endothelium experience physical stress associated with blood flow and play a central role in maintaining vascular integrity and homeostasis in response to hemodynamic forces. Blood flow within vessels is generally laminar and streamlined. However, abrupt changes in the vessel geometry due to branching, sharp turns or stenosis can disturb the laminar blood flow, causing secondary flows in the form of vortices. Such disturbed flow patterns activate pro-inflammatory phenotypes in endothelial cells, damaging the endothelial layer and can lead to atherosclerosis and thrombosis. Here, we report a microfluidic system with integrated ridge-shaped obstacles for generating controllable disturbed flow patterns. This system is used to study the effect of disturbed flow on the cytoskeleton remodeling and nuclear shape and size of cultured human aortic endothelial cells. Our results demonstrate that the generated disturbed flow changes the orientation angle of actin stress fibers and reduces the nuclear size while increases the nuclear circularity

Dielectrophoresis of micro/nano particles using curved microelectrodes

Dielectrophoresis, the induced motion of polarisable particles in non-homogenous electric field, has been proven as a versatile mechanism to transport, immobilise, sort and characterise micro/nano scale particle in microfluidic platforms. The performance of dielectrophoretic (DEP) systems depend on two parameters: the configuration of microelectrodes designed to produce the DEP force and the operating strategies devised to employ this force in such processes. This work summarises the unique features of curved microelectrodes for the DEP manipulation of target particles in microfluidic systems. The curved microelectrodes demonstrate exceptional capabilities including (i) creating strong electric fields over a large portion of their structure, (ii) minimising electro-thermal vortices and undesired disturbances at their tips, (iii) covering the entire width of the microchannel influencing all passing particles, and (iv) providing a large trapping area at their entrance region, as evidenced by extensive numerical and experimental analyses. These microelectrodes have been successfully applied for a variety of engineering and biomedical applications including (i) sorting and trapping model polystyrene particles based on their dimensions, (ii) patterning carbon nanotubes to trap low-conductive particles, (iii) sorting live and dead cells based on their dielectric properties, (iv) real-time analysis of drug-induced cell death, and (v) interfacing tumour cells with environmental scanning electron microscopy to study their morphological properties. The DEP systems based on curved microelectrodes have a great potential to be integrated with the future lab-on-a-chip systems.<br /

Protective and proliferative effects of survivin mutant on differentiated neuroblastoma

This research focused on the neuro-proliferation and protective effects of a survivin mutant. The results showed that this protein binds to microtubules and induces the division and proliferation of neural cells. Furthermore, it protects the neural cells against retinoic acid induced neurotoxicity, activated T-cell apoptosis and oxidative stress

Survivin : a target from brain cancer to neurodegenerative disease

Apoptosis is an important contributing factor during neuronal death in a variety of neurodegenerative disorders, including multiple sclerosis, Parkinson\u27s disease and sciatic nerve injury. Whereas several clinical and preclinical studies have focused on the neuroprotective effects of caspase inhibitors, their clinical benefits are still unclear. Here, we discuss novel alternative strategies to protect neuronal cells from apoptotic death using members of the inhibitors of apoptosis (IAP) family. We specifically review the different roles of survivin, which is an important member of the IAP family that serves a dual role in the inhibition of apoptosis as well as a vital role in mitosis and cell division. Due to the various roles of survivin during cell division and apoptosis, targeting this protein illustrates a new therapeutic window for the treatment of neurodegenerative diseases

Recent advances on the roles of NO in cancer and chronic inflammatory disorders

Nitric oxide (NO) is a short-life molecule produced by the enzyme known as the nitric oxide synthase (NOS), in a reaction that converts arginine and oxygen into citrulline and NO. There are three isoforms of the enzyme: neuronal NOS (nNOS, also called NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). It is now known that each of these isoforms may be expressed in a variety of tissues and cell types. This paper is a review of the current knowledge of various functions of NO in diseases. We discuss in more detail its role in Cancer, the role of NO in myocardial pathophysiology, in central nervous system (CNS) pathologies. Other diseases such as inflammation, asthma, in chronic liver diseases, inflammatory bowel disease (IBD), arthritis, are also discussed. This review also covers the role of NO in cardiovascular, central nervous, pancreas, lung, gut, kidney, myoskeletal and chronic liver diseases (CLD). The ubiquitous role that the simple gas nitric oxide plays in the body, from maintaining vascular homeostasis and fighting infections to acting as a neurotransmitter and its role in cancer, has spurred a lot of interest among researchers all over the world. Nitric oxide plays an important role in the physiologic modulation of coronary artery tone and myocardial function. Nitric oxide from iNOS appears to be a key mediator of such glial-induced neuronal death. The high sensitivity of neurons to NO is partly due to NO causing inhibition of respiration, rapid glutamate release from both astrocytes and neurons, and subsequent excitotoxic death of the neurons.<br /

Design and simulation of an interdigital-chaotic advection micromixer for lab-on-a-chip applications

This paper presents the design and simulation of a novel passive micromixer. The micromixer consists of two inlet tanks, one mixing channel and two outlet channels. In order to maximise the mixing efficiency, the following considerations are made: (i) The inlet tanks are followed by a series of microchannels, in which the flow is split. The microchannels are arranged in an interdigital manner to maximise the contact area between the two flows. (ii) The microchannels attached to the lower inlet tank have an upward slope while those attached to the upper tank have a downward slope. The higher-density flow is fed to the lower inlet tank and gets an upward velocity before entering the mixing channel. (iii) Two triangular barriers are placed within the mixing channel to impose chaotic advection and perturb the less-mixed flow along the top and bottom surfaces of the channel. (iv) Finally, two outlet channels are incorporated to discard the less-mixed flow. Three-dimensional simulations are carried out to evaluate the performance of the micromixer. Simulations are performed in the absence and presence of the gravitational force to analyse the influence of gravity on the micromixer. Mixing efficiencies of greater than 92% are achieved using water and a 1011\u27density biological solvent as the mixing fluids.<br /