World Academy of Science, Engineering and Technology
[Biomedical and Biological Engineering]
Online ISSN : 1307-6892
926 Implementation of CNV-CH Algorithm Using Map-Reduce Approach
Authors: Aishik Deb, Rituparna Sinha
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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing
Procedia PDF Downloads 125925 Computational Model of Human Cardiopulmonary System
Authors: Julian Thrash, Douglas Folk, Michael Ciracy, Audrey C. Tseng, Kristen M. Stromsodt, Amber Younggren, Christopher Maciolek
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The cardiopulmonary system is comprised of the heart, lungs, and many dynamic feedback mechanisms that control its function based on a multitude of variables. The next generation of cardiopulmonary medical devices will involve adaptive control and smart pacing techniques. However, testing these smart devices on living systems may be unethical and exceedingly expensive. As a solution, a comprehensive computational model of the cardiopulmonary system was implemented in Simulink. The model contains over 240 state variables and over 100 equations previously described in a series of published articles. Simulink was chosen because of its ease of introducing machine learning elements. Initial results indicate that physiologically correct waveforms of pressures and volumes were obtained in the simulation. With the development of a comprehensive computational model, we hope to pioneer the future of predictive medicine by applying our research towards the initial stages of smart devices. After validation, we will introduce and train reinforcement learning agents using the cardiopulmonary model to assist in adaptive control system design. With our cardiopulmonary model, we will accelerate the design and testing of smart and adaptive medical devices to better serve those with cardiovascular disease.Keywords: adaptive control, cardiopulmonary, computational model, machine learning, predictive medicine
Procedia PDF Downloads 162924 Relating Symptoms with Protein Production Abnormality in Patients with Down Syndrome
Authors: Ruolan Zhou
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Trisomy of human chromosome 21 is the primary cause of Down Syndrome (DS), and this genetic disease has significantly burdened families and countries, causing great controversy. To address this problem, the research takes an approach in exploring the relationship between genetic abnormality and this disease's symptoms, adopting several techniques, including data analysis and enrichment analysis. It also explores open-source websites, such as NCBI, DAVID, SOURCE, STRING, as well as UCSC, to complement its result. This research has analyzed the variety of genes on human chromosome 21 with simple coding, and by using analysis, it has specified the protein-coding genes, their function, and their location. By using enrichment analysis, this paper has found the abundance of keratin production-related coding-proteins on human chromosome 21. By adopting past researches, this research has attempted to disclose the relationship between trisomy of human chromosome 21 and keratin production abnormality, which might be the reason for common diseases in patients with Down Syndrome. At last, by addressing the advantage and insufficiency of this research, the discussion has provided specific directions for future research.Keywords: Down Syndrome, protein production, genome, enrichment analysis
Procedia PDF Downloads 111923 Knowledge, Attitude and Associated Factors of Practice towards Post Exposure Prophylaxis of HIV Infection among Health Professionals in Yeka and Kazanchis Health Center
Authors: Semira Zeru Haileslassie
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Lack of awareness and practices of PEP treatment were observed among respondents, but they had a better attitude towards PEP. To this end, a formal training for all respondents regarding PEP for HIV prior to their clinical attachments is of utmost importance. The training ought to incorporate a brief clarification with respect to the unpleasant impact of non-adherence that essentially incorporate destitute treatment result and most prominent hazard of resistance and few given as a major cause for non-compliance to PEP, common transient side-effects of PEP and its administrations ought to be cloister educated healthcare specialists to diminish its effect on adherence. Besides, the propensity of detailing needle adhere harm was destitute that needs endeavors to progress. Progressing the culture of detailing and making the detailing handle simple is very necessary. In reality, announcing such wounds as early as conceivable will educate others not to commit same issue once more and, for the most part, will empower stakeholders to intercede the issue sometime prior to it re-occur. At long last, as distant as get up and go utilize has cleared out with so numerous bothers, risk decrease is the foremost choice. With this, taking the increased significance of protective barriers so as to decrease the hazard of exposure to HIV, distinctive stakeholders (the healing center hardware supply chain director, the HIV/ Helps clinic, the clinic chief, hardware and supply quality confirmation group, and other authoritative bodies) ought to work together in co-ordination to secure the supply and guarantee the quality of those crucial protective barriers and to advance demand health laborers to continuously wear protective barriers when exposed to HIV hazard components as well as to dispose appropriately once done. At long last, we prescribe future examiners to conduct planned multicenter studies with extra goals (counting indicator investigation) for way better generalization and result. In spite of satisfactory information and favorable state of mind towards PEP for HIV in most of the respondents, this study uncovered that there were delays in starting, low utilization, and fragmented use of the prescribed PEP. So, health care staff need to progress their practice on PEP of HIV through diverse training program related to PEP of HIV.Keywords: HIV infection, prophylaxis, knowledge, attitude
Procedia PDF Downloads 185922 Ruta graveolens Fingerprints Obtained with Reversed-Phase Gradient Thin-Layer Chromatography with Controlled Solvent Velocity
Authors: Adrian Szczyrba, Aneta Halka-Grysinska, Tomasz Baj, Tadeusz H. Dzido
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Since prehistory, plants were constituted as an essential source of biologically active substances in folk medicine. One of the examples of medicinal plants is Ruta graveolens L. For a long time, Ruta g. herb has been famous for its spasmolytic, diuretic, or anti-inflammatory therapeutic effects. The wide spectrum of secondary metabolites produced by Ruta g. includes flavonoids (eg. rutin, quercetin), coumarins (eg. bergapten, umbelliferone) phenolic acids (eg. rosmarinic acid, chlorogenic acid), and limonoids. Unfortunately, the presence of produced substances is highly dependent on environmental factors like temperature, humidity, or soil acidity; therefore standardization is necessary. There were many attempts of characterization of various phytochemical groups (eg. coumarins) of Ruta graveolens using the normal – phase thin-layer chromatography (TLC). However, due to the so-called general elution problem, usually, some components remained unseparated near the start or finish line. Therefore Ruta graveolens is a very good model plant. Methanol and petroleum ether extract from its aerial parts were used to demonstrate the capabilities of the new device for gradient thin-layer chromatogram development. The development of gradient thin-layer chromatograms in the reversed-phase system in conventional horizontal chambers can be disrupted by problems associated with an excessive flux of the mobile phase to the surface of the adsorbent layer. This phenomenon is most likely caused by significant differences between the surface tension of the subsequent fractions of the mobile phase. An excessive flux of the mobile phase onto the surface of the adsorbent layer distorts the flow of the mobile phase. The described effect produces unreliable, and unrepeatable results, causing blurring and deformation of the substance zones. In the prototype device, the mobile phase solution is delivered onto the surface of the adsorbent layer with controlled velocity (by moving pipette driven by 3D machine). The delivery of the solvent to the adsorbent layer is equal to or lower than that of conventional development. Therefore chromatograms can be developed with optimal linear mobile phase velocity. Furthermore, under such conditions, there is no excess of eluent solution on the surface of the adsorbent layer so the higher performance of the chromatographic system can be obtained. Directly feeding the adsorbent layer with eluent also enables to perform convenient continuous gradient elution practically without the so-called gradient delay. In the study, unique fingerprints of methanol and petroleum ether extracts of Ruta graveolens aerial parts were obtained with stepwise gradient reversed-phase thin-layer chromatography. Obtained fingerprints under different chromatographic conditions will be compared. The advantages and disadvantages of the proposed approach to chromatogram development with controlled solvent velocity will be discussed.Keywords: fingerprints, gradient thin-layer chromatography, reversed-phase TLC, Ruta graveolens
Procedia PDF Downloads 280921 Optimization of Mechanical Properties of Alginate Hydrogel for 3D Bio-Printing Self-Standing Scaffold Architecture for Tissue Engineering Applications
Authors: Ibtisam A. Abbas Al-Darkazly
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In this study, the mechanical properties of alginate hydrogel material for self-standing 3D scaffold architecture with proper shape fidelity are investigated. In-lab built 3D bio-printer extrusion-based technology is utilized to fabricate 3D alginate scaffold constructs. The pressure, needle speed and stage speed are varied using a computer-controlled system. The experimental result indicates that the concentration of alginate solution, calcium chloride (CaCl2) cross-linking concentration and cross-linking ratios lead to the formation of alginate hydrogel with various gelation states. Besides, the gelling conditions, such as cross-linking reaction time and temperature also have a significant effect on the mechanical properties of alginate hydrogel. Various experimental tests such as the material gelation, the material spreading and the printability test for filament collapse as well as the swelling test were conducted to evaluate the fabricated 3D scaffold constructs. The result indicates that the fabricated 3D scaffold from composition of 3.5% wt alginate solution, that is prepared in DI water and 1% wt CaCl2 solution with cross-linking ratios of 7:3 show good printability and sustain good shape fidelity for more than 20 days, compared to alginate hydrogel that is prepared in a phosphate buffered saline (PBS). The fabricated self-standing 3D scaffold constructs measured 30 mm × 30 mm and consisted of 4 layers (n = 4) show good pore geometry and clear grid structure after printing. In addition, the percentage change of swelling degree exhibits high swelling capability with respect to time. The swelling test shows that the geometry of 3D alginate-scaffold construct and of the macro-pore are rarely changed, which indicates the capability of holding the shape fidelity during the incubation period. This study demonstrated that the mechanical and physical properties of alginate hydrogel could be tuned for a 3D bio-printing extrusion-based system to fabricate self-standing 3D scaffold soft structures. This 3D bioengineered scaffold provides a natural microenvironment present in the extracellular matrix of the tissue, which could be seeded with the biological cells to generate the desired 3D live tissue model for in vitro and in vivo tissue engineering applications.Keywords: biomaterial, calcium chloride, 3D bio-printing, extrusion, scaffold, sodium alginate, tissue engineering
Procedia PDF Downloads 104920 Generative Adversarial Network Based Fingerprint Anti-Spoofing Limitations
Authors: Yehjune Heo
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Fingerprint Anti-Spoofing approaches have been actively developed and applied in real-world applications. One of the main problems for Fingerprint Anti-Spoofing is not robust to unseen samples, especially in real-world scenarios. A possible solution will be to generate artificial, but realistic fingerprint samples and use them for training in order to achieve good generalization. This paper contains experimental and comparative results with currently popular GAN based methods and uses realistic synthesis of fingerprints in training in order to increase the performance. Among various GAN models, the most popular StyleGAN is used for the experiments. The CNN models were first trained with the dataset that did not contain generated fake images and the accuracy along with the mean average error rate were recorded. Then, the fake generated images (fake images of live fingerprints and fake images of spoof fingerprints) were each combined with the original images (real images of live fingerprints and real images of spoof fingerprints), and various CNN models were trained. The best performances for each CNN model, trained with the dataset of generated fake images and each time the accuracy and the mean average error rate, were recorded. We observe that current GAN based approaches need significant improvements for the Anti-Spoofing performance, although the overall quality of the synthesized fingerprints seems to be reasonable. We include the analysis of this performance degradation, especially with a small number of samples. In addition, we suggest several approaches towards improved generalization with a small number of samples, by focusing on what GAN based approaches should learn and should not learn.Keywords: anti-spoofing, CNN, fingerprint recognition, GAN
Procedia PDF Downloads 177919 An Optimized Method for 3D Magnetic Navigation of Nanoparticles inside Human Arteries
Authors: Evangelos G. Karvelas, Christos Liosis, Andreas Theodorakakos, Theodoros E. Karakasidis
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In the present work, a numerical method for the estimation of the appropriate gradient magnetic fields for optimum driving of the particles into the desired area inside the human body is presented. The proposed method combines Computational Fluid Dynamics (CFD), Discrete Element Method (DEM) and Covariance Matrix Adaptation (CMA) evolution strategy for the magnetic navigation of nanoparticles. It is based on an iteration procedure that intents to eliminate the deviation of the nanoparticles from a desired path. Hence, the gradient magnetic field is constantly adjusted in a suitable way so that the particles’ follow as close as possible to a desired trajectory. Using the proposed method, it is obvious that the diameter of particles is crucial parameter for an efficient navigation. In addition, increase of particles' diameter decreases their deviation from the desired path. Moreover, the navigation method can navigate nanoparticles into the desired areas with efficiency approximately 99%.Keywords: computational fluid dynamics, CFD, covariance matrix adaptation evolution strategy, discrete element method, DEM, magnetic navigation, spherical particles
Procedia PDF Downloads 129918 Predicting the Diagnosis of Alzheimer’s Disease: Development and Validation of Machine Learning Models
Authors: Jay L. Fu
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Patients with Alzheimer's disease progressively lose their memory and thinking skills and, eventually, the ability to carry out simple daily tasks. The disease is irreversible, but early detection and treatment can slow down the disease progression. In this research, publicly available MRI data and demographic data from 373 MRI imaging sessions were utilized to build models to predict dementia. Various machine learning models, including logistic regression, k-nearest neighbor, support vector machine, random forest, and neural network, were developed. Data were divided into training and testing sets, where training sets were used to build the predictive model, and testing sets were used to assess the accuracy of prediction. Key risk factors were identified, and various models were compared to come forward with the best prediction model. Among these models, the random forest model appeared to be the best model with an accuracy of 90.34%. MMSE, nWBV, and gender were the three most important contributing factors to the detection of Alzheimer’s. Among all the models used, the percent in which at least 4 of the 5 models shared the same diagnosis for a testing input was 90.42%. These machine learning models allow early detection of Alzheimer’s with good accuracy, which ultimately leads to early treatment of these patients.Keywords: Alzheimer's disease, clinical diagnosis, magnetic resonance imaging, machine learning prediction
Procedia PDF Downloads 136917 A Smart CAD Program for Custom Hand Orthosis Generation Based on Anthropometric Relationships
Authors: Elissa D. Ledoux, Eric J. Barth
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Producing custom orthotic devices is a time-consuming and iterative process. Efficiency could be increased with a smart CAD program to rapidly generate custom part files for 3D printing, reducing the need for a skilled orthosis technician as well as the hands-on time required. Anthropometric data for the hand was analyzed in order to determine dimensional relationships and reduce the number of measurements needed to parameterize the hand. Using these relationships, a smart CAD package was developed to produce custom sized hand orthosis parts downloadable for 3D printing. Results showed that the number of anatomical parameters required could be reduced from 8 to 3, and the relationships hold for 5th to 95th percentile male hands. CAD parts regenerate correctly for the same range. This package could significantly impact the orthotics industry in terms of expedited production and reduction of required human resources and patient contact.Keywords: CAD, hand, orthosis, orthotic, rehabilitation robotics, upper limb
Procedia PDF Downloads 210916 Towards Real-Time Classification of Finger Movement Direction Using Encephalography Independent Components
Authors: Mohamed Mounir Tellache, Hiroyuki Kambara, Yasuharu Koike, Makoto Miyakoshi, Natsue Yoshimura
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This study explores the practicality of using electroencephalographic (EEG) independent components to predict eight-direction finger movements in pseudo-real-time. Six healthy participants with individual-head MRI images performed finger movements in eight directions with two different arm configurations. The analysis was performed in two stages. The first stage consisted of using independent component analysis (ICA) to separate the signals representing brain activity from non-brain activity signals and to obtain the unmixing matrix. The resulting independent components (ICs) were checked, and those reflecting brain-activity were selected. Finally, the time series of the selected ICs were used to predict eight finger-movement directions using Sparse Logistic Regression (SLR). The second stage consisted of using the previously obtained unmixing matrix, the selected ICs, and the model obtained by applying SLR to classify a different EEG dataset. This method was applied to two different settings, namely the single-participant level and the group-level. For the single-participant level, the EEG dataset used in the first stage and the EEG dataset used in the second stage originated from the same participant. For the group-level, the EEG datasets used in the first stage were constructed by temporally concatenating each combination without repetition of the EEG datasets of five participants out of six, whereas the EEG dataset used in the second stage originated from the remaining participants. The average test classification results across datasets (mean ± S.D.) were 38.62 ± 8.36% for the single-participant, which was significantly higher than the chance level (12.50 ± 0.01%), and 27.26 ± 4.39% for the group-level which was also significantly higher than the chance level (12.49% ± 0.01%). The classification accuracy within [–45°, 45°] of the true direction is 70.03 ± 8.14% for single-participant and 62.63 ± 6.07% for group-level which may be promising for some real-life applications. Clustering and contribution analyses further revealed the brain regions involved in finger movement and the temporal aspect of their contribution to the classification. These results showed the possibility of using the ICA-based method in combination with other methods to build a real-time system to control prostheses.Keywords: brain-computer interface, electroencephalography, finger motion decoding, independent component analysis, pseudo real-time motion decoding
Procedia PDF Downloads 131915 Towards End-To-End Disease Prediction from Raw Metagenomic Data
Authors: Maxence Queyrel, Edi Prifti, Alexandre Templier, Jean-Daniel Zucker
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Analysis of the human microbiome using metagenomic sequencing data has demonstrated high ability in discriminating various human diseases. Raw metagenomic sequencing data require multiple complex and computationally heavy bioinformatics steps prior to data analysis. Such data contain millions of short sequences read from the fragmented DNA sequences and stored as fastq files. Conventional processing pipelines consist in multiple steps including quality control, filtering, alignment of sequences against genomic catalogs (genes, species, taxonomic levels, functional pathways, etc.). These pipelines are complex to use, time consuming and rely on a large number of parameters that often provide variability and impact the estimation of the microbiome elements. Training Deep Neural Networks directly from raw sequencing data is a promising approach to bypass some of the challenges associated with mainstream bioinformatics pipelines. Most of these methods use the concept of word and sentence embeddings that create a meaningful and numerical representation of DNA sequences, while extracting features and reducing the dimensionality of the data. In this paper we present an end-to-end approach that classifies patients into disease groups directly from raw metagenomic reads: metagenome2vec. This approach is composed of four steps (i) generating a vocabulary of k-mers and learning their numerical embeddings; (ii) learning DNA sequence (read) embeddings; (iii) identifying the genome from which the sequence is most likely to come and (iv) training a multiple instance learning classifier which predicts the phenotype based on the vector representation of the raw data. An attention mechanism is applied in the network so that the model can be interpreted, assigning a weight to the influence of the prediction for each genome. Using two public real-life data-sets as well a simulated one, we demonstrated that this original approach reaches high performance, comparable with the state-of-the-art methods applied directly on processed data though mainstream bioinformatics workflows. These results are encouraging for this proof of concept work. We believe that with further dedication, the DNN models have the potential to surpass mainstream bioinformatics workflows in disease classification tasks.Keywords: deep learning, disease prediction, end-to-end machine learning, metagenomics, multiple instance learning, precision medicine
Procedia PDF Downloads 116914 Loss Function Optimization for CNN-Based Fingerprint Anti-Spoofing
Authors: Yehjune Heo
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As biometric systems become widely deployed, the security of identification systems can be easily attacked by various spoof materials. This paper contributes to finding a reliable and practical anti-spoofing method using Convolutional Neural Networks (CNNs) based on the types of loss functions and optimizers. The types of CNNs used in this paper include AlexNet, VGGNet, and ResNet. By using various loss functions including Cross-Entropy, Center Loss, Cosine Proximity, and Hinge Loss, and various loss optimizers which include Adam, SGD, RMSProp, Adadelta, Adagrad, and Nadam, we obtained significant performance changes. We realize that choosing the correct loss function for each model is crucial since different loss functions lead to different errors on the same evaluation. By using a subset of the Livdet 2017 database, we validate our approach to compare the generalization power. It is important to note that we use a subset of LiveDet and the database is the same across all training and testing for each model. This way, we can compare the performance, in terms of generalization, for the unseen data across all different models. The best CNN (AlexNet) with the appropriate loss function and optimizers result in more than 3% of performance gain over the other CNN models with the default loss function and optimizer. In addition to the highest generalization performance, this paper also contains the models with high accuracy associated with parameters and mean average error rates to find the model that consumes the least memory and computation time for training and testing. Although AlexNet has less complexity over other CNN models, it is proven to be very efficient. For practical anti-spoofing systems, the deployed version should use a small amount of memory and should run very fast with high anti-spoofing performance. For our deployed version on smartphones, additional processing steps, such as quantization and pruning algorithms, have been applied in our final model.Keywords: anti-spoofing, CNN, fingerprint recognition, loss function, optimizer
Procedia PDF Downloads 128913 A Comprehensive Study on the Porosity Effect of Ti-20Zr Alloy Produced by Powder Metallurgy as a Biomaterial
Authors: Eyyup Murat Karakurt, Yan Huang, Mehmet Kaya, Huseyin Demirtas
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In this study, the effect of the porosity effect of Ti-20Zr alloy produced by powder metallurgy as a biomaterial was investigated experimentally. The Ti based alloys (Ti-20%Zr (at.) were produced under 300 MPa, for 6 h at 1200 °C. Afterward, the microstructure of the Ti-based alloys was analyzed by optical analysis, scanning electron microscopy, energy dispersive spectrometry. Moreover, compression tests were applied to determine the mechanical behaviour of samples. As a result, highly porous Ti-20Zr alloys exhibited an elastic modulus close to human bone. The results later were compared theoretically and experimentally.Keywords: porosity effect, Ti based alloys, elastic modulus, compression test
Procedia PDF Downloads 219912 Angiogenic and Immunomodulatory Properties and Phenotype of Mesenchymal Stromal Cells Can Be Regulated by Cytokine Treatment
Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov
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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation
Procedia PDF Downloads 161911 Biodistribution of Fluorescence-Labelled Epidermal Growth Factor Protein from Slow Release Nanozolid Depots in Mouse
Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan
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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid
Procedia PDF Downloads 159910 Deciphering Electrochemical and Optical Properties of Folic Acid for the Applications of Tissue Engineering and Biofuel Cell
Authors: Sharda Nara, Bansi Dhar Malhotra
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Investigation of the vitamins as an electron transfer mediator could significantly assist in merging the area of tissue engineering and electronics required for the implantable therapeutic devices. The present study report that the molecules of folic acid released by Providencia rettgeri via fermentation route under the anoxic condition of the microbial fuel cell (MFC) exhibit characteristic electrochemical and optical properties, as indicated by absorption spectroscopy, photoluminescence (PL), and cyclic voltammetry studies. The absorption spectroscopy has depicted an absorption peak at 263 nm with a small bulge around 293 nm on day two of bacterial culture, whereas an additional peak was observed at 365 nm on the twentieth day. Furthermore, the PL spectra has indicated that the maximum emission occurred at various wavelengths 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm. The change of emission spectra with varying excitation wavelength might be indicating the presence of tunable optical bands in the folic acid molecules co-related with the redox activity of the molecules. The results of cyclic voltammetry studies revealed that the oxidation and reduction occurred at 0.25V and 0.12V, respectively, indicating the electrochemical behavior of the folic acid. This could be inferred that the released folic acid molecules in a MFC might undergo inter as well as intra molecular electron transfer forming different intermediate states while transferring electrons to the electrode surface. Synchronization of electrochemical and optical properties of folic acid molecules could be potentially promising for the designing of electroactive scaffold and biocompatible conductive surface for the applications of tissue engineering and biofuel cells, respectively.Keywords: biofuel cell, electroactivity, folic acid, tissue engineering
Procedia PDF Downloads 121909 Magnetic Navigation of Nanoparticles inside a 3D Carotid Model
Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis
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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.Keywords: artery, drug, nanoparticles, navigation
Procedia PDF Downloads 100908 Characterizing the Rectification Process for Designing Scoliosis Braces: Towards Digital Brace Design
Authors: Inigo Sanz-Pena, Shanika Arachchi, Dilani Dhammika, Sanjaya Mallikarachchi, Jeewantha S. Bandula, Alison H. McGregor, Nicolas Newell
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The use of orthotic braces for adolescent idiopathic scoliosis (AIS) patients is the most common non-surgical treatment to prevent deformity progression. The traditional method to create an orthotic brace involves casting the patient’s torso to obtain a representative geometry, which is then rectified by an orthotist to the desired geometry of the brace. Recent improvements in 3D scanning technologies, rectification software, CNC, and additive manufacturing processes have given the possibility to compliment, or in some cases, replace manual methods with digital approaches. However, the rectification process remains dependent on the orthotist’s skills. Therefore, the rectification process needs to be carefully characterized to ensure that braces designed through a digital workflow are as efficient as those created using a manual process. The aim of this study is to compare 3D scans of patients with AIS against 3D scans of both pre- and post-rectified casts that have been manually shaped by an orthotist. Six AIS patients were recruited from the Ragama Rehabilitation Clinic, Colombo, Sri Lanka. All patients were between 10 and 15 years old, were skeletally immature (Risser grade 0-3), and had Cobb angles between 20-45°. Seven spherical markers were placed at key anatomical locations on each patient’s torso and on the pre- and post-rectified molds so that distances could be reliably measured. 3D scans were obtained of 1) the patient’s torso and pelvis, 2) the patient’s pre-rectification plaster mold, and 3) the patient’s post-rectification plaster mold using a Structure Sensor Mark II 3D scanner (Occipital Inc., USA). 3D stick body models were created for each scan to represent the distances between anatomical landmarks. The 3D stick models were used to analyze the changes in position and orientation of the anatomical landmarks between scans using Blender open-source software. 3D Surface deviation maps represented volume differences between the scans using CloudCompare open-source software. The 3D stick body models showed changes in the position and orientation of thorax anatomical landmarks between the patient and the post-rectification scans for all patients. Anatomical landmark position and volume differences were seen between 3D scans of the patient’s torsos and the pre-rectified molds. Between the pre- and post-rectified molds, material removal was consistently seen on the anterior side of the thorax and the lateral areas below the ribcage. Volume differences were seen in areas where the orthotist planned to place pressure pads (usually at the trochanter on the side to which the lumbar curve was tilted (trochanter pad), at the lumbar apical vertebra (lumbar pad), on the rib connected to the apical vertebrae at the mid-axillary line (thoracic pad), and on the ribs corresponding to the upper thoracic vertebra (axillary extension pad)). The rectification process requires the skill and experience of an orthotist; however, this study demonstrates that the brace shape, location, and volume of material removed from the pre-rectification mold can be characterized and quantified. Results from this study can be fed into software that can accelerate the brace design process and make steps towards the automated digital rectification process.Keywords: additive manufacturing, orthotics, scoliosis brace design, sculpting software, spinal deformity
Procedia PDF Downloads 138907 Hypoxia Tolerance, Longevity and Cancer-Resistance in the Mole Rat Spalax – a Liver Transcriptomics Approach
Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln
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The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.Keywords: cancer, hypoxia, longevity, transcriptomics
Procedia PDF Downloads 149906 An Electrocardiography Deep Learning Model to Detect Atrial Fibrillation on Clinical Application
Authors: Jui-Chien Hsieh
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Background:12-lead electrocardiography(ECG) is one of frequently-used tools to detect atrial fibrillation (AF), which might degenerate into life-threaten stroke, in clinical Practice. Based on this study, the AF detection by the clinically-used 12-lead ECG device has only 0.73~0.77 positive predictive value (ppv). Objective: It is on great demand to develop a new algorithm to improve the precision of AF detection using 12-lead ECG. Due to the progress on artificial intelligence (AI), we develop an ECG deep model that has the ability to recognize AF patterns and reduce false-positive errors. Methods: In this study, (1) 570-sample 12-lead ECG reports whose computer interpretation by the ECG device was AF were collected as the training dataset. The ECG reports were interpreted by 2 senior cardiologists, and confirmed that the precision of AF detection by the ECG device is 0.73.; (2) 88 12-lead ECG reports whose computer interpretation generated by the ECG device was AF were used as test dataset. Cardiologist confirmed that 68 cases of 88 reports were AF, and others were not AF. The precision of AF detection by ECG device is about 0.77; (3) A parallel 4-layer 1 dimensional convolutional neural network (CNN) was developed to identify AF based on limb-lead ECGs and chest-lead ECGs. Results: The results indicated that this model has better performance on AF detection than traditional computer interpretation of the ECG device in 88 test samples with 0.94 ppv, 0.98 sensitivity, 0.80 specificity. Conclusions: As compared to the clinical ECG device, this AI ECG model promotes the precision of AF detection from 0.77 to 0.94, and can generate impacts on clinical applications.Keywords: 12-lead ECG, atrial fibrillation, deep learning, convolutional neural network
Procedia PDF Downloads 109905 Green Synthesis of Silver Nanoparticles Mediated by Plant by-Product Extracts
Authors: Cristian Moisa, Andreea Lupitu, Adriana Csakvari, Dana G. Radu, Leonard Marian Olariu, Georgeta Pop, Dorina Chambre, Lucian Copolovici, Dana Copolovici
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Green synthesis of nanoparticles (NPs) represents a promising, accessible, eco-friendly, and safe process with significant applications in biotechnology, pharmaceutical sciences, and farming. The aim of our study was to obtain silver nanoparticles, using plant wastes extracts resulted in the essential oils extraction process: Thymus vulgaris L., Origanum vulgare L., Lavandula angustifolia L., and in hemp processing for seed and fibre, Cannabis sativa. Firstly, we obtained aqueous extracts of thyme, oregano, lavender, and hemp (two monoicous and one dioicous varieties), all harvested in western part of Romania. Then, we determined the chemical composition of the extracts by liquid-chromatography coupled with diode array and mass spectrometer detectors. The compounds identified in the extracts were in agreement with earlier published data, and the determination of the antioxidant activity of the obtained extracts by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assays confirmed their antioxidant activity due to their total polyphenolic content evaluated by Folin-Ciocalteu assay. Then, the silver nanoparticles (AgNPs) were successfully biosynthesised, as was demonstrated by UV-VIS, FT-IR spectroscopies, and SEM, by reacting AgNO₃ solution and plant extracts. AgNPs were spherical in shape, with less than 30 nm in diameter, and had a good bactericidal activity against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas fluorescens).Keywords: plant wastes extracts, chemical composition, high performance liquid chromatography mass spectrometer, HPLC-MS, scanning electron microscopy, SEM, silver nanoparticles
Procedia PDF Downloads 169904 Task Evoked Pupillary Response for Surgical Task Difficulty Prediction via Multitask Learning
Authors: Beilei Xu, Wencheng Wu, Lei Lin, Rachel Melnyk, Ahmed Ghazi
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In operating rooms, excessive cognitive stress can impede the performance of a surgeon, while low engagement can lead to unavoidable mistakes due to complacency. As a consequence, there is a strong desire in the surgical community to be able to monitor and quantify the cognitive stress of a surgeon while performing surgical procedures. Quantitative cognitiveload-based feedback can also provide valuable insights during surgical training to optimize training efficiency and effectiveness. Various physiological measures have been evaluated for quantifying cognitive stress for different mental challenges. In this paper, we present a study using the cognitive stress measured by the task evoked pupillary response extracted from the time series eye-tracking measurements to predict task difficulties in a virtual reality based robotic surgery training environment. In particular, we proposed a differential-task-difficulty scale, utilized a comprehensive feature extraction approach, and implemented a multitask learning framework and compared the regression accuracy between the conventional single-task-based and three multitask approaches across subjects.Keywords: surgical metric, task evoked pupillary response, multitask learning, TSFresh
Procedia PDF Downloads 135903 Automatic Classification for the Degree of Disc Narrowing from X-Ray Images Using CNN
Authors: Kwangmin Joo
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Automatic detection of lumbar vertebrae and classification method is proposed for evaluating the degree of disc narrowing. Prior to classification, deep learning based segmentation is applied to detect individual lumbar vertebra. M-net is applied to segment five lumbar vertebrae and fine-tuning segmentation is employed to improve the accuracy of segmentation. Using the features extracted from previous step, clustering technique, k-means clustering, is applied to estimate the degree of disc space narrowing under four grade scoring system. As preliminary study, techniques proposed in this research could help building an automatic scoring system to diagnose the severity of disc narrowing from X-ray images.Keywords: Disc space narrowing, Degenerative disc disorders, Deep learning based segmentation, Clustering technique
Procedia PDF Downloads 116902 Improving Pediatric Patient Experience
Authors: Matthew Pleshaw, Caroline Lynch, Caleb Eaton, Ali Kiapour
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The problem addressed in this proposal is that of the lacking comfort and safety of inpatient rooms, specifically at Boston Children’s Hospital, with the implementation of a system that will allow inpatient children to feel more comfortable in the unfamiliar environment of a hospital. The focus is that of advancing and enhancing the healing process for children in a long-term inpatient stay at the hospital, though a combination of announcing a clinician or hospital staff’s arrival utilizing RFID (Fig. 1), and improving communication between clinicians, parents/guardians, patients, etc. by integrating a mobile application.Keywords: Pediatrics, Hospital, RFID, Technology
Procedia PDF Downloads 151901 Skull Extraction for Quantification of Brain Volume in Magnetic Resonance Imaging of Multiple Sclerosis Patients
Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho
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Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper
Procedia PDF Downloads 136900 Facial Recognition Technology in Institutions of Higher Learning: Exploring the Use in Kenya
Authors: Samuel Mwangi, Josephine K. Mule
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Access control as a security technique regulates who or what can access resources. It is a fundamental concept in security that minimizes risks to the institutions that use access control. Regulating access to institutions of higher learning is key to ensure only authorized personnel and students are allowed into the institutions. The use of biometrics has been criticized due to the setup and maintenance costs, hygiene concerns, and trepidations regarding data privacy, among other apprehensions. Facial recognition is arguably a fast and accurate way of validating identity in order to guard protected areas. It guarantees that only authorized individuals gain access to secure locations while requiring far less personal information whilst providing an additional layer of security beyond keys, fobs, or identity cards. This exploratory study sought to investigate the use of facial recognition in controlling access in institutions of higher learning in Kenya. The sample population was drawn from both private and public higher learning institutions. The data is based on responses from staff and students. Questionnaires were used for data collection and follow up interviews conducted to understand responses from the questionnaires. 80% of the sampled population indicated that there were many security breaches by unauthorized people, with some resulting in terror attacks. These security breaches were attributed to stolen identity cases, where staff or student identity cards were stolen and used by criminals to access the institutions. These unauthorized accesses have resulted in losses to the institutions, including reputational damages. The findings indicate that security breaches are a major problem in institutions of higher learning in Kenya. Consequently, access control would be beneficial if employed to curb security breaches. We suggest the use of facial recognition technology, given its uniqueness in identifying users and its non-repudiation capabilities.Keywords: facial recognition, access control, technology, learning
Procedia PDF Downloads 117899 An Effective Modification to Multiscale Elastic Network Model and Its Evaluation Based on Analyses of Protein Dynamics
Authors: Weikang Gong, Chunhua Li
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Dynamics plays an essential role in function exertion of proteins. Elastic network model (ENM), a harmonic potential-based and cost-effective computational method, is a valuable and efficient tool for characterizing the intrinsic dynamical properties encoded in biomacromolecule structures and has been widely used to detect the large-amplitude collective motions of proteins. Gaussian network model (GNM) and anisotropic network model (ANM) are the two often-used ENM models. In recent years, many ENM variants have been proposed. Here, we propose a small but effective modification (denoted as modified mENM) to the multiscale ENM (mENM) where fitting weights of Kirchhoff/Hessian matrixes with the least square method (LSM) is modified since it neglects the details of pairwise interactions. Then we perform its comparisons with the original mENM, traditional ENM, and parameter-free ENM (pfENM) on reproducing dynamical properties for the six representative proteins whose molecular dynamics (MD) trajectories are available in http://mmb.pcb.ub.es/MoDEL/. In the results, for B-factor prediction, mENM achieves the best performance among the four ENM models. Additionally, it is noted that with the weights of the multiscale Kirchhoff/Hessian matrixes modified, interestingly, the modified mGNM/mANM still has a much better performance than the corresponding traditional ENM and pfENM models. As to dynamical cross-correlation map (DCCM) calculation, taking the data obtained from MD trajectories as the standard, mENM performs the worst while the results produced by the modified mENM and pfENM models are close to those from MD trajectories with the latter a little better than the former. Generally, ANMs perform better than the corresponding GNMs except for the mENM. Thus, pfANM and the modified mANM, especially the former, have an excellent performance in dynamical cross-correlation calculation. Compared with GNMs (except for mGNM), the corresponding ANMs can capture quite a number of positive correlations for the residue pairs nearly largest distances apart, which is maybe due to the anisotropy consideration in ANMs. Furtherly, encouragingly the modified mANM displays the best performance in capturing the functional motional modes, followed by pfANM and traditional ANM models, while mANM fails in all the cases. This suggests that the consideration of long-range interactions is critical for ANM models to produce protein functional motions. Based on the analyses, the modified mENM is a promising method in capturing multiple dynamical characteristics encoded in protein structures. This work is helpful for strengthening the understanding of the elastic network model and provides a valuable guide for researchers to utilize the model to explore protein dynamics.Keywords: elastic network model, ENM, multiscale ENM, molecular dynamics, parameter-free ENM, protein structure
Procedia PDF Downloads 113898 Chemical, Structural and Mechanical Optimization of Zr-Based Bulk Metallic Glass for Biomedical Applications
Authors: Eliott Guérin, Remi Daudin, Georges Kalepsi, Alexis Lenain, Sebastien Gravier, Benoit Ter-Ovanessian, Damien Fabregue, Jean-Jacques Blandin
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Due to interesting compromise between mechanical and corrosion properties, Zr-based BMGs are attractive for biomedical applications. However, the enhancement of their glass forming ability (GFA) is often achieved by addition of toxic elements like Ni or Be, which is of course a problem for such applications. Consequently, the development of Ni-free Be-free Zr-based BMGs is of great interest. We have developed a Zr-based (Ni and Be-free) amorphous metallic alloy with an elastic limit twice the one of Ti-6Al-4V. The Zr56Co28Al16 composition exhibits a yield strength close to 2 GPa and low Young’s modulus (close to 90 GPa) [1-2]. In this work, we investigated Niobium (Nb) addition through substitution of Zr up to 8 at%. Cobalt substitution has already been reported [3], but we chose Zr substitution to preserve the glass forming ability. In this case, we show that the glass forming ability for 5 mm diameters rods is maintained up to 3 at% of Nb substitution using suction casting in cooper moulds. Concerning the thermal stability, we measure a strong compositional dependence on the glass transition (Tg). Using DSC analysis (heating rate 20 K/min), we show that the Tg rises from 752 K for 0 at% of Nb to 759 K for 3 at% of Nb. Yet, the thermal range between Tg and the crystallisation temperature (Tx) remains almost unchanged from 33 K to 35 K. Uniaxial compression tests on 2 mm diameter pillars and 3 points bending (3PB) tests on 1 mm thick plates are performed to study the Nb addition on the mechanical properties and the plastic behaviour. With these tests, an optimal Nb concentration is found, improving both plasticity and fatigue resistance. Through interpretations of DSC measurements, an attempt is made to correlate the modifications of the mechanical properties with the structural changes. The optimized chemical, structural and mechanical properties through Nb addition are encouraging to develop the potential of this BMG alloy for biomedical applications. For this purpose, we performed polarisation, immersion and cytotoxicity tests. The figure illustrates the polarisation response of Zr56Co28Al16, Zr54Co28Al16Nb2 and TA6V as a reference after 2h of open circuit potential. The results show that the substitution of Zr by a small amount of Nb significantly improves the corrosion resistance of the alloy.Keywords: metallic glasses, amorphous metal, medical, mechanical resistance, biocompatibility
Procedia PDF Downloads 140897 Tumor Cell Detection, Isolation and Monitoring Using Bi-Layer Magnetic Microfluidic Chip
Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari
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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation
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