World Academy of Science, Engineering and Technology

Authors: Arash Dalili, Hamed Tahmouressi, Mina Hoorfar

Abstract:

Advances in lab-on-a-chip (LOC) devices have led to significant advances in the manipulation, separation, and isolation of particles and cells. Among the different active and passive particle manipulation methods, dielectrophoresis (DEP) has been proven to be a versatile mechanism as it is label-free, cost-effective, simple to operate, and has high manipulation efficiency. DEP has been applied for a wide range of biological and environmental applications. A popular form of DEP devices is the continuous manipulation of particles by using co-planar slanted electrodes, which utilizes a sheath flow to focus the particles into one side of the microchannel. When particles enter the DEP manipulation zone, the negative DEP (nDEP) force generated by the slanted electrodes deflects the particles laterally towards the opposite side of the microchannel. The lateral displacement of the particles is dependent on multiple parameters including the geometry of the electrodes, the width, length and height of the microchannel, the size of the particles and the throughput. In this study, COMSOL Multiphysics® modeling along with experimental studies are used to investigate the effect of the aforementioned parameters. The electric field between the electrodes and the induced DEP force on the particles are modelled by COMSOL Multiphysics®. The simulation model is used to show the effect of the DEP force on the particles, and how the geometry of the electrodes (width of the electrodes and the gap between them) plays a role in the manipulation of polystyrene microparticles. The simulation results show that increasing the electrode width to a certain limit, which depends on the height of the channel, increases the induced DEP force. Also, decreasing the gap between the electrodes leads to a stronger DEP force. Based on these results, criteria for the fabrication of the electrodes were found, and soft lithography was used to fabricate interdigitated slanted electrodes and microchannels. Experimental studies were run to find the effect of the flow rate, geometrical parameters of the microchannel such as length, width, and height as well as the electrodes’ angle on the displacement of 5 um, 10 um and 15 um polystyrene particles. An empirical equation is developed to predict the displacement of the particles under different conditions. It is shown that the displacement of the particles is more for longer and lower height channels, lower flow rates, and bigger particles. On the other hand, the effect of the angle of the electrodes on the displacement of the particles was negligible. Based on the results, we have developed an optimum design (in terms of efficiency and throughput) for three size separation of particles.

Keywords: COMSOL Multiphysics, Dielectrophoresis, Microfluidics, Particle separation

Procedia PDF Downloads 168

Authors: Khandoker Akib Mohammad

Abstract:

While analyzing time-to-event data, it is possible that a certain fraction of subjects will never experience the event of interest, and they are said to be cured. When this feature of survival models is taken into account, the models are commonly referred to as cure models. In the presence of covariates, the conditional survival function of the population can be modelled by using the cure model, which depends on the probability of being uncured (incidence) and the conditional survival function of the uncured subjects (latency), and a combination of logistic regression and Cox proportional hazards (PH) regression is used to model the incidence and latency respectively. In this paper, we have shown the asymptotic normality of the profile likelihood estimator via asymptotic expansion of the profile likelihood and obtain the explicit form of the variance estimator with an implicit function in the profile likelihood. We have also shown the efficient score function based on projection theory and the profile likelihood score function are equal. Our contribution in this paper is that we have expressed the efficient information matrix as the variance of the profile likelihood score function. A simulation study suggests that the estimated standard errors from bootstrap samples (SMCURE package) and the profile likelihood score function (our approach) are providing similar and comparable results. The numerical result of our proposed method is also shown by using the melanoma data from SMCURE R-package, and we compare the results with the output obtained from the SMCURE package.

Keywords: Cox PH model, cure model, efficient score function, EM algorithm, implicit function, profile likelihood

Procedia PDF Downloads 132

Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

Abstract:

Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

Procedia PDF Downloads 102

Authors: Shilpee Jain, Sachin Latiyan, Kaushik Suneet

Abstract:

Unlike traditional robots, medical microbots are not only smaller in size, but they also possess various unique properties, for example, biocompatibility, stability in the biological fluids, navigation opposite to the bloodstream, wireless control over locomotion, etc. The idea behind their usage in the medical field was to build a minimally invasive method for addressing the post-operative complications, including longer recovery time, infection eruption and pain. Herein, the present study demonstrates the fabrication of dual nature magneto-conducting Fe3O4 magnetic nanoparticles (MNPs) and SU8 derived carbon-based Janus microbots for the efficient intracellular delivery of biomolecules. The low aspect ratio with feature size 2-5 μm microbots were fabricated by using a photolithography technique. These microbots were pyrolyzed at 900°C, which converts SU8 into amorphous carbon. The pyrolyzed microbots have dual properties, i.e., the half part is magneto-conducting and another half is only conducting for sufficing the therapeutic payloads efficiently with the application of external electric/magnetic field stimulations. For the efficient intracellular delivery of the microbots, the size and aspect ratio plays a significant role. However, on a smaller scale, the proper control over movement is difficult to achieve. The dual nature of Janus microbots allowed to control its maneuverability in the complex fluids using external electric as well as the magnetic field. Interestingly, Janus microbots move faster with the application of an external electric field (44 µm/s) as compared to the magnetic field (18 µm/s) application. Furthermore, these Janus microbots exhibit auto-fluorescence behavior that will help to track their pathway during navigation. Typically, the use of MNPs in the microdevices enhances the tendency to agglomerate. However, the incorporation of Fe₃O₄ MNPs in the pyrolyzed carbon reduces the chances of agglomeration of the microbots. The biocompatibility of the medical microbots, which is the essential property of any biosystems, was determined in vitro using HeLa cells. The microbots were found to compatible with HeLa cells. Additionally, the intracellular uptake of microbots was higher in the presence of an external electric field as compared to without electric field stimulation. In summary, the cytocompatible Janus microbots were fabricated successfully. They are stable in the biological fluids, wireless controllable navigation with the help of a few Guess external magnetic fields, their movement can be tracked because of autofluorescence behavior, they are less susceptible to agglomeration and higher cellular uptake could be achieved with the application of the external electric field. Thus, these carriers could offer a versatile platform to suffice the therapeutic payloads under wireless actuation.

Keywords: amorphous carbon, electric/magnetic stimulations, Janus microbots, magnetic nanoparticles, minimally invasive procedures

Procedia PDF Downloads 115

Authors: Nonita Sarin, K.J.Singh, Anuj Kumar, Davinder Singh

Abstract:

Polymeric 3D hydrogels have pivotal role in bone tissue regeneration applications. Hydrogels behave similar to the living tissues because they have large water imbibing capacity in swollen state and adjust their shape according to the tissues during tissue formation after implantation. On the other hand, hydrogels are very soft, fragile and lack mechanical strength. Incorporation of bioceramics can improve mechanical strength. Furthermore, bioceramics synthesized by sol gel technique may enhance the apatite formation and degradation rates which can lead to the increase in faster rates for new bone and tissue regeneration. Simulated body fluid (SBF) induces the poly-condensation of silanol groups which leads to formation of silica matrix and provide active sites for the precipitation of Ca2+ and PO43- ions to form apatite layer which is similar to mineral form of bone. Therefore, authors have synthesized bioceramic incorporated Polyacrylamide-carboxymethylcellulose hydrogels by free radical polymerization and bioceramic compositions of xSrO-(36-x)CaO-45SiO2-ySeO3-(12-y)P2O5-7MgO (where x=0,4 and y=0,2 mol%) were synthesized by sol gel technique. Bioceramics incorporated in polymer matrix induces quicker apatite formation during immersion in SBF by raising the pH with the release of alkaline ions during ion exchange process and the apatite formation takes place in alkaline medium. The behavior of samples PABC-0 (without bioceramics) and PABC-20 (with 20 wt% bioceramics) were evaluated by X-Ray Diffraction and FTIR. In term of bioactivity, it was observed that PABC-20 has shown hydroxyapatite (HA) formation on 1st day of immersion whereas, PABC-0 was shown apatite formation on 7th day of immersion in SBF. The rapid rate of HA growth on 1st day of immersion in SBF signifies easy regeneration of damaged bone tissues. Degradation studies have been undertaken in Phosphate Buffer Saline and PABC-20 exhibited slower degradation rate up to 9%as compared to PABC-0 up to 18%. Slower degradation rate is suitable for new tissue regeneration and cell attachment. Also, Zeta potential studies have been employed to check the surface charge and it has been observed that samples carry negative charge when immersed in SBF. In addition, the swelling test of the samples have been performed and relative swelling ratio % observed for PABC-0 is 607% and PABC-20 is 305%. This indicates that the incorporation of bioceramics leads to the filling up of the voids in between the polymer matrix which in result reduces porosity and increase the mechanical strength by filling the voids. The porosity of PABC-0 is 84% and PABC-20 is 72%. PABC-20 sample demonstrates that bioceramics incorporation reduce the porosity and improves mechanical strength. Also, maximum in vitro cell viability up to 98% with MG63 cell line has been observed which indicate that the bioceramic incorporated hydrogel(PABC-20) provide the alkaline medium which is suitable environment for cell growth.

Keywords: hydrogels, hydroxyapatite, MG63 cell line, zeta potential

Procedia PDF Downloads 131

Authors: Wadha Alqahtani

Abstract:

In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

Procedia PDF Downloads 106

Authors: Divya Pradip Roy, Md. Zahirul Alam Chowdhury

Abstract:

Electromyography (EMG) sensors are generally used to record the electrical activity produced by skeletal muscles. The conventional EMG sensors available in the market are expensive. This research suggests a low cost EMG sensor design which can be built with simple devices within our reach. In this research, one instrumentation amplifier, two high pass filters, two low pass filters and an inverting amplifier is connected sequentially. The output from the circuit exhibits electrical potential generated by the muscle cells when they are neurologically activated. This electromyography signal is used to control prosthetic devices, identifying neuromuscular diseases and for various other purposes.

Keywords: EMG, high pass filter, instrumentation amplifier, inverting amplifier, low pass filter, neuromuscular

Procedia PDF Downloads 161

Authors: Aura Maria Lopera Echavarria, Angela Maria Lema Perez, Daniela Medrano David, Pedronel Araque Marin, Marta Elena Londoño Lopez

Abstract:

Bone regeneration is the process by which the formation of new bone is stimulated. Bone fractures can originate at any time due to trauma, infections, tumors, congenital malformations or skeletal diseases. Currently there are different strategies to treat bone defects that in some cases, regeneration does not occur on its own. That is why they are treated with bone substitutes, which provide a necessary environment for the cells to synthesize new bone. The Demineralized Bone Matrix (DBM) is widely used as a bone implant due to its good properties, such as osteoinduction and bioactivity. However, the use of DBM is limited, because its presentation is powder, which is difficult to implant with precision and is susceptible to migrating to other sites through blood flow. That is why the DBM is commonly incorporated into a variety of vehicles or carriers. The objective of this project is to evaluate the bioactive and confinement properties of a bone substitute based on demineralized bone matrix (DBM). Also, structural and morphological properties were evaluated. Bone substitute was obtained from EIA Biomaterials Laboratory of EIA University and the DBM was facilitated by Tissue Bank Foundation. Morphological and structural properties were evaluated by scanning electron microscopy (SEM), X-ray diffraction (DRX) and Fourier transform infrared spectroscopy with total attenuated reflection (FTIR-ATR). Water absorption capacity and degradation were also evaluated during three months. The cytotoxicity was evaluated by the MTT test. The bioactivity of the bone substitute was evaluated through immersion of the samples in simulated body fluid during four weeks. Confinement tests were performed on tibial fragments of a human donor with bone defects of determined size, to ensure that the substitute remains in the defect despite the continuous flow of fluid. According of the knowledge of the authors, the methodology for evaluating samples in a confined environment has not been evaluated before in real human bones. The morphology of the samples showed irregular surface and presented some porosity. DRX confirmed a semi-crystalline structure. The FTIR-ATR determined the organic and inorganic phase of the sample. The degradation and absorption measurements stablished a loss of 3% and 150% in one month respectively. The MTT showed that the system is not cytotoxic. Apatite clusters formed from the first week were visualized by SEM and confirmed by EDS. These calcium phosphates are necessary to stimulate bone regeneration and thanks to the porosity of the developed material, osteinduction and osteoconduction are possible. The results of the in vitro evaluation of the confinement of the material showed that the migration of the bone filling to other sites is negligible, although the samples were subjected to the passage of simulated body fluid. The bone substitute, putty type, showed stability, is bioactive, non-cytotoxic and has handling properties for specialists at the time of implantation. The obtained system allows to maintain the osteoinductive properties of DBM and it can fill completely fractures in any way; however, it does not provide a structural support, that is, it should only be used to treat fractures without requiring a mechanical load.

Keywords: bone regeneration, cytotoxicity, demineralized bone matrix, hydrogel

Procedia PDF Downloads 110

Authors: Saman Namvarrechi, Armin A. Dormeny, Javad Dargahi, Mojtaba Kahrizi

Abstract:

Since last two decades, minimally invasive surgery (MIS) has grown significantly due to its advantages compared to the traditional open surgery like less physical pain, faster recovery time and better healing condition around incision regions; however, one of the important challenges in MIS is getting an effective sensing feedback within the patient’s body during operations. Therefore, surgeons need efficient tactile sensing like determining the hardness of contact tissue for investigating the patient’s health condition. In such a case, MIS tactile sensors are preferred to be able to provide force/pressure sensing, force position, lump detection, and softness sensing. Among different pressure sensor technologies, the piezoelectric operating principle is the fittest for MIS’s instruments, such as catheters. Using PVDF with its copolymer, TrFE, as a piezoelectric material, is a common method of design and fabrication of a tactile sensor due to its ease of implantation and biocompatibility. In this research, PVDF-TrFE polymer is deposited via spin-coating method and treated with various post-deposition processes to investigate its piezoelectricity and amount of electroactive β phase. These processes include different post thermal annealing, the effect of spin-coating speed, different layer of deposition, and the presence of additional hydrate salt. According to FTIR spectroscopy and SEM images, the amount of the β phase and porosity of each sample is determined. In addition, the optimum experimental study is established by considering every aspect of the fabrication process. This study clearly shows the effective way of deposition and fabrication of a tactile PVDF-TrFE based sensor and an enhancement methodology to have a higher β phase and piezoelectric constant in order to have a better sense of touch at the end effector of biomedical devices.

Keywords: β phase, minimally invasive surgery, piezoelectricity, PVDF-TrFE, tactile sensor

Procedia PDF Downloads 113

Authors: Niamh Higgins, Dawn Howard

Abstract:

The Irish agri-food sector is of major importance to Ireland’s manufacturing sector and to the Irish economy through employment and the exporting of animal products worldwide. Infectious diseases and parasites have an impact on farm animal health causing profitability and productivity to be affected. For the sustainability of Irish dairy farming, there must be the highest standard of animal health. There can be a lack of information in accounting for > 1% of complete microbial diversity in an environment. There is the tendency of culture-based methods of microbial identification to overestimate the prevalence of species which grow easily on an agar surface. There is a need for new technologies to address these issues to assist with animal health. Metagenomic approaches provide information on both the whole genome and transcriptome present through DNA sequencing of total DNA from environmental samples producing high determination of functional and taxonomic information. Nanopore Next Generation Technologies have the ability to be powerful sequencing technologies. They provide high throughput, low material requirements and produce ultra-long reads, simplifying the experimental process. The aim of this study is to use a metagenomics approach to analyze dairy cattle faecal samples using the Oxford Nanopore MinION Next Generation Sequencer and to establish an in-house pipeline for metagenomic characterization of complex samples. Faecal samples will be obtained from Irish dairy farms, DNA extracted and the MinION will be used for sequencing, followed by bioinformatics analysis. Of particular interest, will be the parasite Buxtonella sulcata, which there has been little research on and which there is no research on its presence on Irish dairy farms. Preliminary results have shown the ability of the MinION to produce hundreds of reads in a relatively short time frame of eight hours. The faecal samples were obtained from 90 dairy cows on a Galway farm. The results from Oxford Nanopore ‘What’s in my pot’ (WIMP) using the Epi2me workflow, show that from a total of 926 classified reads, 87% were from the Kingdom Bacteria, 10% were from the Kingdom Eukaryota, 3% were from the Kingdom Archaea and < 1% were from the Kingdom Viruses. The most prevalent bacteria were those from the Genus Acholeplasma (71 reads), Bacteroides (35 reads), Clostridium (33 reads), Acinetobacter (20 reads). The most prevalent species present were those from the Genus Acholeplasma and included Acholeplasma laidlawii (39 reads) and Acholeplasma brassicae (26 reads). The preliminary results show the ability of the MinION for the identification of microorganisms to species level coming from a complex sample. With ongoing optimization of the pipe-line, the number of classified reads are likely to increase. Metagenomics has the potential in animal health for diagnostics of microorganisms present on farms. This would support wprevention rather than a cure approach as is outlined in the DAFMs National Farmed Animal Health Strategy 2017-2022.

Keywords: animal health, buxtonella sulcata, infectious disease, irish dairy cattle, metagenomics, minION, next generation sequencing

Procedia PDF Downloads 138

Authors: Ali Mirtaghavi, Andy Baldwin, Rajendarn Muthuraj, Jack Luo

Abstract:

Recent advances in biomaterials have led to utilizing biopolymers to develop 3D scaffolds in tissue regeneration. One of the major challenges of designing biomaterials for 3D scaffolds is to mimic the building blocks similar to the extracellular matrix (ECM) of the native tissues. Biopolymer based aerogels obtained by freeze-drying have shown to provide structural similarities to the ECM owing to their 3D format and a highly porous structure with interconnected pores, similar to the ECM. Gelatin (GEL) is known to be a promising biomaterial with inherent regenerative characteristics owing to its chemical similarities to the ECM in native tissue, biocompatibility abundance, cost-effectiveness and accessible functional groups, which makes it facile for chemical modifications with other biomaterials to form biocomposites. Despite such advantages, gelatin offers poor mechanical properties, sensitive enzymatic degradation and high viscosity at room temperature which limits its application and encourages its use to develop biocomposites. Hydrophilic biomass-based cellulose nanofibrous (CNF) has been explored to use as suspension for biocomposite aerogels for the development of 3D porous structures with excellent mechanical properties, biocompatibility and slow enzymatic degradation. In this work, CNF biocomposite aerogels with various ratios of CNF:GEL) (90:10, 70:30 and 50:50) were prepared by freeze-drying technique, and their properties were investigated in terms of physicochemical, mechanical and biological characteristics. Epichlorohydrin (EPH) was used to investigate the effect of chemical crosslinking on the molecular interaction of CNF: GEL, and its effects on physicochemical, mechanical and biological properties of the biocomposite aerogels. Ultimately, chemical crosslinking helped to improve the mechanical resilience of the resulting aerogels. Amongst all the CNF-GEL composites, the crosslinked CNF: GEL (70:30) biocomposite was found to be favourable for cell attachment and viability. It possessed highly porous structure (porosity of ~93%) with pore sizes ranging from 16-110 µm, adequate mechanical properties (compression modulus of ~47 kPa) and optimal biocompatibility both in-vitro and in-vivo, as well as controlled enzymatic biodegradation, high water penetration, which could be considered a suitable option for wound healing application. In-vivo experiments showed improvement on inflammation and foreign giant body cell reaction for the crosslinked CNF: GEL (70:30) compared to the other samples. This could be due to the superior interaction of CNF with gelatin through chemical crosslinking, resulting in more optimal in-vivo improvement. In-vitro cell culture investigation on human dermal fibroblasts showed satisfactory 3D cell attachment over time. Overall, it has been observed that the developed CNF: GEL aerogel can be considered as a potential scaffold for soft tissue regeneration application.

Keywords: 3D scaffolds, aerogels, Biocomposites , tissue engineering

Procedia PDF Downloads 124

Authors: Laura Norfolk, Georgina Zimbitas, Jan Sefcik, Sarah Staniland

Abstract:

Magnetite nanoparticles (MNP) have been an area of increasing research interest due to their extensive applications in industry, such as in carbon capture, water purification, and crucially, the biomedical industry. The use of MNP in the biomedical industry is rising, with studies on their effect as Magnetic resonance imaging contrast agents, drug delivery systems, and as hyperthermic cancer treatments becoming prevalent in the nanomaterial research community. Particles used for biomedical purposes must meet stringent criteria; the particles must have consistent shape and size between particles. Variation between particle morphology can drastically alter the effective surface area of the material, making it difficult to correctly dose particles that are not homogeneous. Particles of defined shape such as octahedral and cubic have been shown to outperform irregular shaped particles in some applications, leading to the need to synthesize particles of defined shape. In nature, highly homogeneous MNP are found within magnetotactic bacteria, a unique bacteria capable of producing magnetite nanoparticles internally under ambient conditions. Biomineralisation proteins control the properties of the MNPs, enhancing their homogeneity. One of these proteins, Mms6, has been successfully isolated and used in vitro as an additive in room-temperature co-precipitation reactions (RTCP) to produce particles of defined mono-dispersed size & morphology. When considering future industrial scale-up it is crucial to consider the costs and feasibility of an additive, as an additive that is not readily available or easily synthesized at a competitive price will not be sustainable. As such, additives selected for this research are inspired by the functional groups of biomineralisation proteins, but cost-effective, environmentally friendly, and compatible with scale-up. Diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), and pentaethylenehexamine (PEHA) have been successfully used in RTCP to modulate the properties of particles synthesized, leading to the formation of octahedral nanoparticles with no use of organic solvents, heating, or toxic precursors. By extending this principle to a fluidic system, ongoing research will reveal whether the amine additives can also exert morphological control in an environment which is suited toward higher particle yield. Two fluidic systems have been employed; a peristaltic turbulent flow mixing system suitable for the rapid production of MNP, and a macrofluidic system for the synthesis of tailored nanomaterials under a laminar flow regime. The presence of the amine additives in the turbulent flow system in initial results appears to offer similar morphological control as observed under RTCP conditions, with higher proportions of octahedral particles formed. This is a proof of concept which may pave the way to green synthesis of tailored MNP on an industrial scale. Mms6 and amine additives have been used in the macrofluidic system, with Mms6 allowing magnetite to be synthesized at unfavourable ferric ratios, but no longer influencing particle size. This suggests this synthetic technique while still benefiting from the addition of additives, may not allow additives to fully influence the particles formed due to the faster timescale of reaction. The amine additives have been tested at various concentrations, the results of which will be discussed in this paper.

Keywords: bioinspired, green synthesis, fluidic, magnetite, morphological control, scale-up

Procedia PDF Downloads 108

Authors: Mojtaba Mirmontazemi, Habibollah Dadgar

Abstract:

Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.

Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)

Procedia PDF Downloads 103

Authors: Kitti Szoke, Laszlo Szoke, Attila Czompa, Arpad Tosaki, Istvan Lekli

Abstract:

Autophagy plays an important role in cardiac hypertrophy, which is one of the most common causes of heart failure in the world. This self-degradative catabolic process, responsible for protein quality control, balancing sources of energy at critical times, and elimination of damaged organelles. The autophagic activity can be triggered by starvation, oxidative stress, or pharmacological agents, like rapamycin. This induced autophagy can promote cell survival during starvation or pathological stress. In this study, it is investigated the effect of the induced autophagic process on angiotensin induced hypertrophic H9c2 cells. In our study, it is used H9c2 cells as an in vitro model. To induce hypertrophy, cells were treated with 10000 nM angiotensin-II, and to activate autophagy, 100 nM rapamycin treatment was used. The following groups were formed: 1: control, 2: 10000 nM AT-II, 3: 100 nM rapamycin, 4: 100 nM rapamycin pretreatment then 10000 nM AT-II. The cell viability was examined via MTT (cell proliferation assay) assay. The cells were stained with rhodamine-conjugated phalloidin and DAPI to visualize F-actin filaments and cell nuclei then the cell size alteration was examined in a fluorescence microscope. Furthermore, the expression levels of autophagic and apoptotic proteins such as Beclin-1, p62, LC3B-II, Cleaved Caspase-3 were evaluated by Western blot. MTT assay result suggests that the used pharmaceutical agents in the tested concentrations did not have a toxic effect; however, at group 3, a slight decrement was detected in cell viability. In response to AT-II treatment, a significant increase was detected in the cell size; cells became hypertrophic. However, rapamycin pretreatment slightly reduced the cell size compared to group 2. Western blot results showed that AT-II treatment-induced autophagy, because the increased expression of Beclin-1, p62, LC3B-II were observed. However, due to the incomplete autophagy, the apoptotic Cleaved Caspase-3 expression also increased. Rapamycin pretreatment up-regulated Beclin-1 and LC3B-II, down-regulated p62 and Cleaved Caspase-3, indicating that rapamycin-induced autophagy can restore the normal autophagic flux. Taken together, our results suggest that rapamycin activated autophagy reduces angiotensin-II induced hypertrophy.

Keywords: angiotensin-II, autophagy, H9c2 cell line, hypertrophy, rapamycin

Procedia PDF Downloads 135

Authors: Ramji Kalidoss, Snekhalatha Umapathy, V. Dhinakaran, J. M. Mathana

Abstract:

Chemi-resistive sensors used in breathalyzers have become a hotspot between the international breath research communities. These sensors exhibit a significant change in its resistance depending on the temperature it gets heated thus demanding high power leading to non-portable instrumentation. In this work, numerical simulation to identify the suitable combination of substrate and heater profile using COMSOL multiphysics was studied. Ni-Cr and Pt-100 joule resistive heater with various profiles were studied beneath the square and circular alumina substrates. The temperature distribution was uniform throughout the square substrate with the meander shaped pt100 heater with 48 mW power consumption for 200 oC. Moreover, this heater profile induced minimal stress on the substrate with 0.5 mm thick. A novel Graphene based ternary metal oxide nanocomposite (GO/SnO2/TiO2) was coated on the optimized substrate and heater to elucidate the response of diabetes biomarker (acetone). The sensor exhibited superior gas sensing performance towards acetone in the exhaled breath concentration range for diabetes (0.25 – 3 ppm). These results indicated the importance of substrate and heater properties along with sensing material for low power portable breathalyzers.

Keywords: Breath Analysis, Chemical Sensors, Diabetes Mellitus, Graphene Nanocomposites, Heater, Substrate

Procedia PDF Downloads 127

Authors: Miguel Contreras, David Long, Will Bachman

Abstract:

Background: Microscopy plays a central role in cell and developmental biology. In particular, fluorescence microscopy can be used to visualize specific cellular components and subsequently quantify their morphology through development of virtual-cell models for study of effects of mechanical forces on cells. However, there are challenges with these imaging experiments, which can make it difficult to quantify cell morphology: inconsistent results, time-consuming and potentially costly protocols, and limitation on number of labels due to spectral overlap. To address these challenges, the objective of this project is to develop an automatic computational machine learning pipeline to predict cellular components morphology for virtual-cell generation based on fluorescence cell membrane confocal z-stacks. Methods: Registered confocal z-stacks of nuclei and cell membrane of endothelial cells, consisting of 20 images each, were obtained from fluorescence confocal microscopy and normalized through software pipeline for each image to have a mean pixel intensity value of 0.5. An open source machine learning algorithm, originally developed to predict fluorescence labels on unlabeled transmitted light microscopy cell images, was trained using this set of normalized z-stacks on a single CPU machine. Through transfer learning, the algorithm used knowledge acquired from its previous training sessions to learn the new task. Once trained, the algorithm was used to predict morphology of nuclei using normalized cell membrane fluorescence images as input. Predictions were compared to the ground truth fluorescence nuclei images. Results: After one week of training, using one cell membrane z-stack (20 images) and corresponding nuclei label, results showed qualitatively good predictions on training set. The algorithm was able to accurately predict nuclei locations as well as shape when fed only fluorescence membrane images. Similar training sessions with improved membrane image quality, including clear lining and shape of the membrane, clearly showing the boundaries of each cell, proportionally improved nuclei predictions, reducing errors relative to ground truth. Discussion: These results show the potential of pre-trained machine learning algorithms to predict cell morphology using relatively small amounts of data and training time, eliminating the need of using multiple labels in immunofluorescence experiments. With further training, the algorithm is expected to predict different labels (e.g., focal-adhesion sites, cytoskeleton), which can be added to the automatic machine learning pipeline for direct input into Principal Component Analysis (PCA) for generation of virtual-cell mechanical models.

Keywords: cell morphology prediction, computational machine learning, fluorescence microscopy, virtual-cell models

Procedia PDF Downloads 194

Authors: Safoin Aktaou, Aya Al Masri, Kamel Guerchouche, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: In the ‘Magnetic Resonance Imaging (MRI)’ department, all workers involved in preparing the patient, setting it up, tunnel cleaning, etc. are likely to be exposed to ‘ElectroMagnetic fields (EMF)’ emitted by the MRI device. Exposure to EMF can cause adverse radio-biological effects to workers. The purpose of this study is to propose an organizational process to manage and control EMF risks. Materials and methods: The study was conducted at seven MRI departments using machines with 1.5 and 3 Tesla magnetic fields. We assessed the exposure of each one by measuring the two electromagnetic fields (static and dynamic) at different distances from the MRI machine both inside and around the examination room. Measurement values were compared with British and American references (those of the UK's ‘Medicines and Healthcare Regulatory Agency (MHRA)’ and the ‘American Radiology Society (ACR)’). Results: Following the results of EMF measurements and their comparison with the recommendations of learned societies, a zoning system that adapts to needs of different MRI services across the country has been proposed. In effect, three risk areas have been identified within the MRI services. This has led to the development of a good practice guide related to the magnetic protection of MRI workers. Conclusion: The guide established by our study is a standard that allows MRI workers to protect themselves against the risk of electromagnetic fields.

Keywords: comparison with international references, measurement of electromagnetic fields, magnetic protection of workers, magnetic resonance imaging

Procedia PDF Downloads 155

Authors: Stefaan Carpentier, Aya Al Masri, Fabrice Leroy, Thibault Julien, Safoin Aktaou, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: During an 'Interventional Radiology (IR)' procedure, the patient's skin-dose may become very high for a burn, necrosis, and ulceration to appear. In order to prevent these deterministic effects, a prediction of the peak skin-dose for the patient is important in order to improve the post-operative care to be given to the patient. The objective of this study is to estimate, before the intervention, the patient dose for ‘Chronic Total Occlusion (CTO)’ procedures by selecting relevant clinical indicators. Materials and methods: 103 procedures were performed in the ‘Interventional Cardiology (IC)’ department using a Siemens Artis Zee image intensifier that provides the Air Kerma of each IC exam. Peak Skin Dose (PSD) was measured for each procedure using radiochromic films. Patient parameters such as sex, age, weight, and height were recorded. The complexity index J-CTO score, specific to each intervention, was determined by the cardiologist. A correlation method applied to these indicators allowed to specify their influence on the dose. A predictive model of the dose was created using multiple linear regressions. Results: Out of 103 patients involved in the study, 5 were excluded for clinical reasons and 2 for placement of radiochromic films outside the exposure field. 96 2D-dose maps were finally used. The influencing factors having the highest correlation with the PSD are the patient's diameter and the J-CTO score. The predictive model is based on these parameters. The comparison between estimated and measured skin doses shows an average difference of 0.85 ± 0.55 Gy for doses of less than 6 Gy. The mean difference between air-Kerma and PSD is 1.66 Gy ± 1.16 Gy. Conclusion: Using our developed method, a first estimate of the dose to the skin of the patient is available before the start of the procedure, which helps the cardiologist in carrying out its intervention. This estimation is more accurate than that provided by the Air-Kerma.

Keywords: chronic total occlusion procedures, clinical experimentation, interventional radiology, patient's peak skin dose

Procedia PDF Downloads 127

Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

Abstract:

Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

Procedia PDF Downloads 138

Authors: Aya Al Masri, Stefaan Carpentier, Fabrice Leroy, Thibault Julien, Safoin Aktaou, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: During an 'Interventional Radiology (IR)' procedure, the patient's skin-dose may become very high for a burn, necrosis and ulceration to appear. In order to prevent these deterministic effects, an accurate calculation of the patient skin-dose mapping is essential. For most machines, the 'Dose Area Product (DAP)' and fluoroscopy time are the only information available for the operator. These two parameters are a very poor indicator of the peak skin dose. We developed a mathematical model that reconstructs the magnitude (delivered dose), shape, and localization of each irradiation field on the patient skin. In case of critical dose exceeding, the system generates warning alerts. We present the results of its comparison with clinical studies. Materials and methods: Two series of comparison of the skin-dose mapping of our mathematical model with clinical studies were performed: 1. At a first time, clinical tests were performed on patient phantoms. Gafchromic films were placed on the table of the IR machine under of PMMA plates (thickness = 20 cm) that simulate the patient. After irradiation, the film darkening is proportional to the radiation dose received by the patient's back and reflects the shape of the X-ray field. After film scanning and analysis, the exact dose value can be obtained at each point of the mapping. Four experimentation were performed, constituting a total of 34 acquisition incidences including all possible exposure configurations. 2. At a second time, clinical trials were launched on real patients during real 'Chronic Total Occlusion (CTO)' procedures for a total of 80 cases. Gafchromic films were placed at the back of patients. We performed comparisons on the dose values, as well as the distribution, and the shape of irradiation fields between the skin dose mapping of our mathematical model and Gafchromic films. Results: The comparison between the dose values shows a difference less than 15%. Moreover, our model shows a very good geometric accuracy: all fields have the same shape, size and location (uncertainty < 5%). Conclusion: This study shows that our model is a reliable tool to warn physicians when a high radiation dose is reached. Thus, deterministic effects can be avoided.

Keywords: clinical experimentation, interventional radiology, mathematical model, patient's skin-dose mapping.

Procedia PDF Downloads 131

Authors: Aya Al Masri, Naima Oubenali, Safoin Aktaou, Thibault Julien, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: The increased number of performed 'Computed Tomography (CT)' examinations raise public concerns regarding associated stochastic risk to patients. In its Publication 102, the ‘International Commission on Radiological Protection (ICRP)’ emphasized the importance of managing patient dose, particularly from repeated or multiple examinations. We developed a Dose Archiving and Communication System that gives multiple dose indexes (organ dose, effective dose, and skin-dose mapping) for patients undergoing radiological imaging exams. The aim of this study is to compare the organ dose values given by our software for patients undergoing CT exams with those of another software named "VirtualDose". Materials and methods: Our software uses Monte Carlo simulations to calculate organ doses for patients undergoing computed tomography examinations. The general calculation principle consists to simulate: (1) the scanner machine with all its technical specifications and associated irradiation cases (kVp, field collimation, mAs, pitch ...) (2) detailed geometric and compositional information of dozens of well identified organs of computational hybrid phantoms that contain the necessary anatomical data. The mass as well as the elemental composition of the tissues and organs that constitute our phantoms correspond to the recommendations of the international organizations (namely the ICRP and the ICRU). Their body dimensions correspond to reference data developed in the United States. Simulated data was verified by clinical measurement. To perform the comparison, 270 adult patients and 150 pediatric patients were used, whose data corresponds to exams carried out in France hospital centers. The comparison dataset of adult patients includes adult males and females for three different scanner machines and three different acquisition protocols (Head, Chest, and Chest-Abdomen-Pelvis). The comparison sample of pediatric patients includes the exams of thirty patients for each of the following age groups: new born, 1-2 years, 3-7 years, 8-12 years, and 13-16 years. The comparison for pediatric patients were performed on the “Head” protocol. The percentage of the dose difference were calculated for organs receiving a significant dose according to the acquisition protocol (80% of the maximal dose). Results: Adult patients: for organs that are completely covered by the scan range, the maximum percentage of dose difference between the two software is 27 %. However, there are three organs situated at the edges of the scan range that show a slightly higher dose difference. Pediatric patients: the percentage of dose difference between the two software does not exceed 30%. These dose differences may be due to the use of two different generations of hybrid phantoms by the two software. Conclusion: This study shows that our software provides a reliable dosimetric information for patients undergoing Computed Tomography exams.

Keywords: adult and pediatric patients, computed tomography, organ dose calculation, software comparison

Procedia PDF Downloads 147

Authors: Aya Al Masri, Kamel Guerchouche, Youssef Laynaoui, Safoin Aktaou, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: Mobile C-arms move throughout operating rooms of the operating theater. Being designed to move between rooms, they are not equipped with relays to retrieve the exposition information and export it outside the room. Therefore, no light signaling is available outside the room to warn the X-ray emission for staff. Inadvertent exposition of staff outside the operating theater is a real problem for radiation protection. The French standard NFC 15-160 require that: (1) access to any room containing an X-ray emitting device must be controlled by a light signage so that it cannot be inadvertently crossed, and (2) setting up an emergency button to stop the X-ray emission. This study presents a system that we developed to meet these requirements and the results of its clinical test. Materials and methods: The system is composed of two communicating boxes: o The "DetectBox" is to be installed inside the operating theater. It identifies the various operation states of the C-arm by analyzing its power supply signal. The DetectBox communicates (in wireless mode) with the second box (AlertBox). o The "AlertBox" can operate in socket or battery mode and is to be installed outside the operating theater. It detects and reports the state of the C-arm by emitting a real time light signal. This latter can have three different colors: red when the C-arm is emitting X-rays, orange when it is powered on but does not emit X-rays, and green when it is powered off. The two boxes communicate on a radiofrequency link exclusively carried out in the ‘Industrial, Scientific and Medical (ISM)’ frequency bands and allows the coexistence of several on-site warning systems without communication conflicts (interference). Taking into account the complexity of performing electrical works in the operating theater (for reasons of hygiene and continuity of medical care), this system (having a size <10 cm²) works in complete safety without any intrusion in the mobile C-arm and does not require specific electrical installation work. The system is equipped with emergency button that stops X-ray emission. The system has been clinically tested. Results: The clinical test of the system shows that: it detects X-rays having both high and low energy (50 – 150 kVp), high and low photon flow (0.5 – 200 mA: even when emitted for a very short time (<1 ms)), Probability of false detection < 10-5, it operates under all acquisition modes (continuous, pulsed, fluoroscopy mode, image mode, subtraction and movie mode), it is compatible with all C-arm models and brands. We have also tested the communication between the two boxes (DetectBox and AlertBox) in several conditions: (1) Unleaded room, (2) leaded room, and (3) rooms with particular configuration (sas, great distances, concrete walls, 3 mm of lead). The result of these last tests was positive. Conclusion: This system is a reliable tool to alert the staff present outside the operating room for X-ray emission and insure their radiation protection.

Keywords: Clinical test, Inadvertent staff exposition, Light signage, Operating theater

Procedia PDF Downloads 118

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

Abstract:

The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 104

Authors: Haile F. Darge, Hsieh C. Tsai

Abstract:

The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

Procedia PDF Downloads 119

Authors: Sachin Singh, Thomas Penzel, Dinesh Nandan

Abstract:

Accurate identification of Sleep Apnea Hypopnea Syndrom Diagnosis is difficult problem for human expert because of variability among persons and unwanted noise. This paper proposes the diagonosis of Sleep Apnea Hypopnea Syndrome (SAHS) using airflow, ECG, Pulse and SaO2 signals. The features of each type of these signals are extracted using statistical methods and ANN learning methods. These extracted features are used to approximate the patient's Apnea Hypopnea Index(AHI) using sample signals in model. Advance signal processing is also applied to snore sound signal to locate snore event and SaO2 signal is used to support whether determined snore event is true or noise. Finally, Apnea Hypopnea Index (AHI) event is calculated as per true snore event detected. Experiment results shows that the sensitivity can reach up to 96% and specificity to 96% as AHI greater than equal to 5.

Keywords: neural network, AHI, statistical methods, autoregressive models

Procedia PDF Downloads 112

Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

Abstract:

In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

Procedia PDF Downloads 119

Authors: Dina Helmy El-Ghonemy, Thanaa Hamed Ali

Abstract:

The aim of this study was to purify and characterize a keratinolytic enzyme produced by Aspergillus sp. DHE7 cultured in basal medium containing chicken feather as substrate. The enzyme was purified through ammonium sulfate saturation of 60%, followed by gel filtration chromatography in Sephadex G-100, with a 16.4-purification fold and recovery yield of 52.2%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the purified enzyme is a monomeric enzyme with an apparent molecular mass of 30 kDa — the purified keratinase of Aspergillus sp. DHE7 exhibited activity in a broad range of pH (7- 9) and temperature (40℃-60℃) profiles with an optimal activity at pH eight and 50℃. The keratinolytic activity was inhibited by protease inhibitors such as phenylmethylsulfonyl fluoride and ethylenediaminetetraacetate, while no reduction of activity was detected by the addition of dimethyl sulfoxide (DMSO). Bivalent cations, Ca²⁺ and Mn²⁺, were able to greatly enhance the activity of keratinase by 125.7% and 194.8%, respectively, when used at one mM final concentration. On the other hand, Cu²⁺ and Hg²⁺ inhibited the enzyme activity, which might be indicative of essential vicinal sulfhydryl groups of the enzyme for productive catalysis. Furthermore, the purified keratinase showed significant stability and compatibility against the tested commercial detergents at 37ºC. Therefore, these results suggested that the purified keratinase from Aspergillus sp. DHE7 may have potential use in the detergent industry and should be of interest in the processing of poultry feather waste.

Keywords: Aspergillus sp. DHE7, biochemical characterization, keratinase, purification, waste management

Procedia PDF Downloads 116

Authors: Talbi Mohammed, Oustous Aziz, Ben Messaoud Mounir, Sebihi Rajaa, Khalis Mohammed

Abstract:

Background: Breast cancer is the leading cause of death for women around the world. Screening mammography is the reference examination, due to its sensitivity for detecting small lesions and micro-calcifications. Therefore, it is essential to ensure quality mammographic examinations with the most optimal dose. These conditions depend on the choice of exposure parameters. Clinically, practices must be evaluated in order to determine the most appropriate exposure parameters. Material and Methods: We performed our measurements on a mobile mammography unit (PLANMED Sofie-classic.) in Morocco. A solid dosimeter (AGMS Radcal) and a MTM 100 phantom allow to quantify the delivered dose and the image quality. For image quality assessment, scores are defined by the rate of visible inserts (MTM 100 phantom), obtained and compared for each acquisition. Results: The results show that the parameters of the mammography unit on which we have made our measurements can be improved in order to offer a better compromise between image quality and breast dose. The last one can be reduced up from 13.27% to 22.16%, while preserving comparable image quality.

Keywords: Mammography, Breast Dose, Image Quality, Phantom

Procedia PDF Downloads 163

Authors: Madalina Postaru, Alexandra Tucaliuc, Dan Cascaval, Anca Irina Galaction

Abstract:

Ergosterol (ergosta-5,7,22-trien-3β-ol) is the precursor of vitamin D2 (ergocalciferol), known as provitamin D2 as it is converted under UV radiation to this vitamin. The natural sources of ergosterol are mainly the yeasts (Saccharomyces sp., Candida sp.), but it can be also found in fungus (Claviceps sp.) or plants (orchids). As ergosterol is mainly accumulated in yeast cell membranes, especially in free form in the plasma-membrane, and the chemical synthesis of ergosterol does not represent an efficient method for its production, this study aimed to analyze the influence of aeration efficiency on ergosterol production by S. cerevisiae in batch and fed-batch fermentations, by considering different levels of mixing intensity, aeration rate, and n-dodecane concentration. Our previous studies on ergosterol production by S. cerevisiae in batch and fed-batch fermentation systems indicated that the addition of n-dodecane led to the increase of almost 50% of this sterol concentration, the highest productivity being reached for the fed-batch process. The experiments were carried out in a laboratory stirred bioreactor, provided with computer-controlled and recorded parameters. In batch fermentation system, the study indicated that the oxygen mass transfer coefficient, kLa, is amplified for about 3 times by increasing the volumetric concentration of n-dodecane from 0 to 15%. Moreover, the increase of dissolved oxygen concentration by adding n-dodecane leads to the diminution for 3.5 times of the produced alcohol amount. In fed-batch fermentation process, the positive influence of hydrocarbon on oxygen transfer rate is amplified mainly at its higher concentration level, as the result of the increased yeasts cells amount. Thus, by varying n-dodecane concentration from 0 to 15% vol., the kLa value increase becomes more important than for the batch fermentation, being of 4 times

Keywords: ergosterol, yeast fermentation, n-dodecane, oxygen-vector

Procedia PDF Downloads 109

Authors: Binh T. T. Nguyen, Zhenyu Li, Eric Yap, Yi Zhang, Ai-Qun Liu

Abstract:

Silicon-photonic-sensor system is an emerging class of analytical technologies that use evanescent field wave to sensitively measure the slight difference in the surrounding environment. The wavelength shift induced by local refractive index change is used as an indicator in the system. These devices can be served as sensors for a wide variety of chemical or biomolecular detection in clinical and environmental fields. In our study, a system including a silicon-based micro-ring resonator, microfluidic channel, and optical processing is designed, fabricated for biomolecule detection. The system is demonstrated to detect Clostridium botulinum type A neurotoxin (BoNT) in different water sources. BoNT is one of the most toxic substances known and relatively easily obtained from a cultured bacteria source. The toxin is extremely lethal with LD50 of about 0.1µg/70kg intravenously, 1µg/ 70 kg by inhalation, and 70µg/kg orally. These factors make botulinum neurotoxins primary candidates as bioterrorism or biothreat agents. It is required to have a sensing system which can detect BoNT in a short time, high sensitive and automatic. For BoNT detection, silicon-based micro-ring resonator is modified with a linker for the immobilization of the anti-botulinum capture antibody. The enzymatic reaction is employed to increase the signal hence gains sensitivity. As a result, a detection limit to 30 pg/mL is achieved by our silicon-photonic sensor within a short period of 80 min. The sensor also shows high specificity versus the other type of botulinum. In the future, by designing the multifunctional waveguide array with fully automatic control system, it is simple to simultaneously detect multi-biomaterials at a low concentration within a short period. The system has a great potential to apply for online, real-time and high sensitivity for the label-free bimolecular rapid detection.

Keywords: biotoxin, photonic, ring resonator, sensor

Procedia PDF Downloads 108