Sara Baratchi

Dielectrophoretic platforms for bio-microfluidic systems.

Dielectrophoresis, the induced motion of polarisable particles in a nonuniform electric field, has been proven as a versatile mechanism to transport, accumulate, separate and characterise micro/nano scale bioparticles in microfluidic systems. The integration of DEP systems into the microfluidics enables the inexpensive, fast, highly sensitive, highly selective and label-free detection and analysis of target bioparticles. This review provides an in-depth overview of state-of-the-art dielectrophoretic (DEP) platforms integrated into microfluidics aimed towards different biomedical applications. It classifies the current DEP systems in terms of different microelectrode configurations and operating strategies devised to generate and employ DEP forces in such processes, and compares the features of each approach. Finally, it suggests the future trends and potential applications of DEP systems in single cell analysis, stem cell research, establishing novel devices, and realising fully DEP-activated lab-on-a-chip systems.

Dielectrophoretic manipulation and separation of microparticles using curved microelectrodes

This paper presents the development and experimental analysis of a dielectrophoresis (DEP) system, which is used for the manipulation and separation of microparticles in liquid flow. The system is composed of arrays of microelectrodes integrated to a microchannel. Novel curved microelectrodes are symmetrically placed with respect to the centre of the microchannel with a minimum gap of 40u2009μm. Computational fluid dynamics method is utilised to characterise the DEP field and predict the dynamics of particles. The performance of the system is assessed with microspheres of 1, 5 and 12u2009μm diameters. When a high‐frequency potential is applied to microelectrodes a spatially varying electric field is induced in the microchannel, which creates the DEP force. Negative‐DEP behaviour is observed with particles being repelled from the microelectrodes. The particles of different dimensions experience different DEP forces and thus settle to separate equilibrium zones across the microchannel. Experiments demonstrate the capability of the system as a field flow fraction tool for sorting microparticles according to their dimensions and dielectric properties.

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’s 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.

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 Parkinsons and Alzheimers 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.

Proliferative and protective effects of SurR9-C84A on differentiated neural cells

Targeting survivin has the ability to inhibit apoptosis and regulate mitosis for the protection of neuronal cells, and it offers several advantages for neuronal repair and protection. We found that the BIR motif mutant of survivin (SurR9-C84A) can bind to microtubules and regulate their stability, induce cell division, increase proliferation and activate the expression of cell cycle and neuronal markers in differentiated SK-N-SH and HCN-2 neurons. We further showed the protective effects of SurR9-C84A against post differentiation retinoic acid induced neurotoxicity. These abilities of SurR9-C84A offer a great potential for future neuronal repair therapy.

Particle trapping using dielectrophoretically patterned carbon nanotubes.

This study presents the dielectrophoretic (DEP) assembly of multi‐walled carbon nanotubes (MWCNTs) between curved microelectrodes for the purpose of trapping polystyrene microparticles within a microfluidic system. Under normal conditions, polystyrene particles exhibit negative DEP behaviour and are repelled from microelectrodes. Interestingly, the addition of MWCNTs to the system alters this situation in two ways: first, they coat the surface of particles and change their dielectric properties to exhibit positive DEP behaviour; second, the assembled MWCNTs are highly conductive and after the deposition serve as extensions to the microelectrodes. They establish an array of nanoelectrodes that initiates from the edge of microelectrodes and grow along the electric field lines. These nanoelectrodes can effectively trap the MWCNT‐coated particles, since they cover a large portion of the microchannel bottom surface and also create a much stronger electric field than the primary microelectrodes as confirmed by our numerical simulations. We will show that the presence of MWCNT significantly changes performance of the system, which is investigated by trapping sample polystyrene particles with plain, COOH and goat anti‐mouse IgG surfaces.

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.

Novel survivin mutant protects differentiated SK-N-SH human neuroblastoma cells from activated T-cell neurotoxicity

Currently, there are no known treatments for protection of axonal loss associated with neuroinflammatory diseases such as multiple sclerosis (MS). Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins that its neuroprotective effects have not been studied. We demonstrate here that SurR9-C84A, a survivin mutant, exhibits a neuroprotective role against the cytotoxic effects of activated T-cell infiltrates, such as granzyme B (GrB). The activated T-cell supernatants induce toxicity on differentiated SK-N-SH cells, which is associated with the loss of Ca(2+) homeostasis, the increased population of dead cells, mitochondrial membrane depolarisation, and the accelerated expression of cyclinD1, caspase3 and Fas, as observed for most apoptotic cells. Alternatively, the pre-treatment with SurR9-C84A reduces the population of dead cells by balancing the cytosolic Ca(2+) homeostasis, decreasing the level of mitochondrial depolarisation, and also reducing the expression of cyclinD1 and caspase3. Our findings suggest that SurR9-C84A has a neuroprotective effect against the cytotoxins existing in activated T-cell supernatants including GrB.

Review: At a glance: Cellular biology for engineers

Engineering contributions have played an important role in the rise and evolution of cellular biology. Engineering technologies have helped biologists to explore the living organisms at cellular and molecular levels, and have created new opportunities to tackle the unsolved biological problems. There is now a growing demand to further expand the role of engineering in cellular biology research. For an engineer to play an effective role in cellular biology, the first essential step is to understand the cells and their components. However, the stumbling block of this step is to comprehend the information given in the cellular biology literature because it best suits the readers with a biological background. This paper aims to overcome this bottleneck by describing the human cell components as micro-plants that form cells as micro-bio-factories. This concept can accelerate the engineers comprehension of the subject. In this paper, first the structure and function of different cell components are described. In addition, the engineering attempts to mimic various cell components through numerical modelling or physical implementation are highlighted. Next, the interaction of different cell components that facilitate complicated chemical processes, such as energy generation and protein synthesis, are described. These complex interactions are translated into simple flow diagrams, generally used by engineers to represent multi-component processes.

Reorientation of microfluidic channel enables versatile dielectrophoretic platforms for cell manipulations.

Dielectrophoresis is a versatile tool for the sorting, immobilization, and characterization of cells in microfluidic systems. The performance of dielectrophoretic systems strongly relies on the configuration of microelectrodes, which produce a nonuniform electric field. However, once fabricated, the microelectrodes cannot be reconfigured to change the characteristics of the system. Here, we show that the reorientation of the microfluidic channel with respect to the microelectrodes can be readily utilized to alter the characteristics of the system. This enables us to change the location and density of immobilized viable cells across the channel, release viable cells along customized numbers of streams within the channel, change the deflection pattern of nonviable cells along the channel, and improve the sorting of viable and nonviable cells in terms of flow throughput and efficiency of the system. We demonstrate that the reorientation of the microfluidic channel is an effective tool to create versatile dielectrophoretic platforms using the same microelectrode design.