Detection of Electrooxidation Products in Microfluidic Devices Using Raman Spectroscopy

I. Introduction Advances in wearable electronics, functional nanocomposite polymers, flexible microfluidics, and commercial polymer microfluidics are reported on a daily basis. However, much of this research is field-specific, despite the enormous potential that the convergence of these research areas has for the future of health care, worker safety, food safety, consumer devices, and commercial microfluidics. We present an innovative approach of powerful, general-purpose frameworks that facilitate interfacing of nanocomposite polymer-based, microfluidic, and electronic devices on flexible polymer, textile, or industrial polymer platforms. Such approaches offer practical solutions for areas such as safety lighting and health monitors for safety vests; heart monitors and perspiration monitors for athletic clothing; and other applications in real-time wearable bioelectric and biochemical monitoring. II. Wearable Microfluidic and Electronic Frameworks A. Wearable bioelectric sensors Intense research into wearable electronics has resulted in many innovative devices and systems, e.g.: flexible polyimide or Kapton printed circuit boards (PCBs) [1]; roll-to-roll foil and other printed devices [2]; printing and weaving of textiles [3]; and special geometries for flexible interconnect between rigid components [4]. We have investigated conductive nanocomposite polymers and metal transfer processes for wearable bioelectric sensors [5, 6]. These technologies can be employed in, for example, conformable and wearable systems for electrocardiogram (ECG) [5], tissue impedance [7] and pressure [8] sensors. Unlike many other techniques, the technology and materials employed for our devices are highly compatible with clothing-based textiles. B. Wearable microfluidics Much less research has been performed in the emerging area of wearable microfluidics. Traditionally, microfluidic devices are fabricated in rigid substrates or flexible materials such as polydimethylsiloxane (PDMS) that are bonded to rigid substrates. Free-standing PDMS devices are developed for, e.g., perspiration sensors [9]; however, such processes typically require long fabrication times, equipment in a cleanroom facility, and difficulty with integration onto textiles. Other devices employ porous materials or microneedles to deliver biofluids, e.g., perspiration or interstitial fluid, by capillary forces [10]; however, such devices are limited in fluid collection or are too invasive. Wearable textile-based devices have been recently demonstrated that use the textile itself as a fluidic “channel” [11]; however, such devices are dependent on the fluidic characteristics of the fabric. To overcome these limitations and facilitate the development of fully flexible, wearable, and durable microfluidic devices that can be used for a wider variety of applications, we have developed a printing-based fabrication process that employs screen printable plastisol ink [12]. This process is demonstrated for simple multi-level microfluidic devices toward the goal of fully wearable microfluidic systems. III. Summary Many methods have been developed for microelectronic and microfluidic devices in rigid or flexible packages (e.g., [13, 14, 15]). However, such technologies suffer from difficult integration and/or limited flexibility, limited geometries, limited microfluidic sample size, and/or difficult integration, especially on textile-based substrates. The technologies we present offer simple and compatible printing-based and transfer processes for microelectronic and microfluidic frameworks that facilitate cost-effective development of durable wearable biomedical systems. References Y. Chuo, et. al., IEEE Transactions Biomedical Circuits Systems 4(5):281-94 (2010).K. Jain, et. al., Proceedings of the IEEE 93(8):15000-10 (2005).F. Carpi, et. al., IEEE Transactions Information Technology Biomedicine 9(3):295-318 (2005).M. Gonzalez, et. al., Microelectronics Reliability 51:1069-76 (2011).D. Chung, et. al. Proc. SPIE 9060, (2014); doi:10.1117/12.2046548.D. Hilbich, et. al., Proc. SPIE 98020R (2016); doi:10.1117/12.2219284.D. Chung, et. al., J Electrochemical Society 161(2):B3071-76 (2014).A. Rahbar, et. al., Proc. SPIE 90600O (2014); doi:10.1117/12.2044342.J. Choi, et. al., Adv Healthcare Mater 6:1601355 (2017).F. Benito-Lopez, et. al., Procedia Chemistry 1(1):1103-1106 (2009).A. Nilghaz, et. al., Lab Chip 12:209-218 (2012).D. Chung & B.L. Gray, J Micromech Microeng, 27(11), (2017).S. Cheng., et. al., Advanced Functional Materials 21(12):2282-90 (2011).M. Scholles, et. al., Proc. of SPIE 7593:75930C-2 (2013).A. Wu, et. al., Lab Chip 10:519-521 (2010).

Background. Circulating tumor cells (CTCs) and their clusters have been regarded as potential targets for therapies and subjects for identifying certain mechanisms of cancer metastasis. Mouse models have been especially useful tools to investigate the process of metastasis, since they are easier to control and are less variable compared to clinical patient samples. Therefore, it is of interest to extract and study CTCs and CTC clusters from such mouse models. However, most isolation systems are designed and tested for human blood and cell lines. Sized-based methods of CTC isolation have been optimized for human cell lines, but mouse CTCs are generally smaller in size (i.e., ~14 µm EO771 breast cancer cells). Therefore, mouse cell separation necessitates a varied protocol for CTC isolation. We used mouse blood and EO771, a mouse breast cancer cell line, to demonstrate the isolation of mouse CTCs from mouse blood using a sized-based microfluidic device. We also validated the presence of endogenous CTCs and CTC-neutrophil clusters in a tumor bearing mouse model. Methods. Our microfluidic device employs inertial migration in a straight channel segment (150 µm × 50 µm × 24 mm) to isolate CTCs from blood samples. We spiked 100 and 1000 ZsGreen-expressing EO771 cells in 5 × diluted blood containing tdTomato-expressing neutrophils, easily distinguishing CTCs from the red-colored neutrophils. To enumerate the recovered cells, we used Cytospin to concentrate the cells into a glass slide. Lastly, we used hydrodynamic traps to capture CTC clusters from tumor-bearing mouse blood. The blood was extracted from the posterior vena cava of the mice at the endpoint experiment. Results. We achieved an overall recovery rate of 22-29%, which combines the recovery of the isolation device and the Cytospin. Here, we enumerate cells only after their extraction from the collection tube outside of the isolation device. Other methods with higher capture efficiency enumerate the recovered CTCs before they are harvested from the isolation device which is not always representative of the number of cells that are analyzed. We were also able to discover endogenous CTC-neutrophil clusters from tumor-bearing mice which we distinguished apart with anti-EpCAM staining of CTCs (green) and anti-Ly6G (red) staining of neutrophils. Conclusion. We demonstrated and optimized a procedure for isolating mouse-derived CTCs from naïve mice blood and CTC-neutrophil clusters from tumor-bearing mice with our microfluidic isolation devices, as opposed to the isolation of human CTCs as in other sized-based isolation systems. In future studies, we aim to continue to use our microfluidic devices to capture and study CTC and CTC clusters. Citation Format: Celine Macaraniag, Jian Zhou, Ian Papautsky, Jing Li, William Putzbach, Nissim Hay. Microfluidic isolation and capture of circulating tumor cells and clusters from mouse blood. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5598.

High-throughput fabrication of graphically encoded hydrogel microparticles is achieved by combining flow contact lithography in a multichannel microfluidic device and a high capacity 25 mm LED UV source. Production rates of chemically homogeneous particles are improved by two orders of magnitude. Additionally, the custom-built contact lithography instrument provides an affordable solution for patterning complex microstructures on surfaces.

where the biological activity is expressed as the reciprocal of the concentration that elicit a given biological, pharmacological or toxicological endpoint such as ED 50 (effective dose 50%), IC 50 (inhibitory concentration 50%) or LD 50 (lethal dose 50%), and where x i is the i predictor (from a set of n predictors) raised to the powers from 1 to m and weighted by its coefficients a ij obtained from a multivariate statistical fitting [4,5]. Usually, most of the coefficients a ij can be zero, leading to much simpler looking QSAR models than the general form in Equation 1, as in the example below. Often, other functions of x i are used in the QSAR model such as the logarithmic or exponential function instead of a simple power expansion as in Equation 1. As a simple illustration of the operation of Equation 1 is the following example of a QSAR model to predict the inhibitory effect of 3-nitroflavones (3NF) based on a single predictor, x (the energy of the highest occupied molecular orbital, E HOMO ) raised to the power 1 (see also [6]). Invasive tumor growth and metastasis are sustained by angiogenesis (the formation of new blood vessels [7,8]), which led Folkman to suggest anticancer therapies by the use of antiangiogenic agents [9,10]. Lichtenberg et al. have shown that the antiangiogenicity of six 3NF is correlated with the energies of the highest occupied molecular orbital, E HOMO, the lower the oxidation potential the greater the inhibitory effects on several biomarkers of angiogenesis [11,12]. These authors report the following correlation between the E HOMO and the IC 50 of six 3NF for inhibition of proliferation of microvascular endothelial HMEC-1 cells after 72 h of incubation:

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices (μPADs), have fostered a new spectrum of microfluidic devices for point-of-care diagnosis and biosensing. In this paper, we report diatomite microfluidic devices, which consist of multi-scale hierarchically porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect hazardous chemicals. The diatomite microfluidic devices in this work are fabricated by simple spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30μm2. As the most unique feature, our diatomite microfluidic devices can simultaneously perform on-chip chromatography to separate small molecules from complex samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to ppb-level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10ppb) from human plasma. This pioneering work proves the exclusive advantage of diatomite microfluidic devices as emerging microfluidic devices for chemical and biomedical sensing.

A facile method for the fabrication of glass-PDMS-glass sandwich microfluidic devices by sacrificial molding

The financial support for this work was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) through Research Grants awarded to Drs. Bellehumeur and Gu.

The polymer electrolyte membrane (PEM) electrolyzer is a promising technology that reduces water into hydrogen and oxygen, from which the hydrogen is captured and stored for use in fuel cells. One of the challenging issues in PEM electrolyzers is flow inhibition of liquid water within the porous gas diffusion layer (GDL), due to the formation of oxygen bubbles (1). The bubbles block pores within the GDL, limiting the transport of liquid water to the catalyst layer, which in turn negatively affects the electrolyzer performance (2). Moreover, the presence of the oxygen bubbles can increase the solution resistance, inhibit electron transfer, and consequently increase ohmic losses, leading to efficiency reduction (1).Investigation of the oxygen bubbles behavior generated at the anode side of the PEM electrolyzer in operational pressure and temperature can give us a more accurate insight for predicting its influence on the performance. A number of promising studies on bubble nucleation and detachment have been done over the past few years. Various numerical techniques were introduced and improved to increase the accuracy of the bubble interface tracking such as volume-of-fluid (VOF) (3), moment-of-fluid (MOF) (4), and level-set (LS) methods (5).In this study, a numerical simulation has been performed to mimic the nucleation, growth and detachment of the oxygen bubbles in electrolyzers. Utilizing a state-of-the-art multiphase algorithm (6), a three-dimensional, two-phase computational algorithm was developed using the LS method to track the oxygen bubble interface expansion. To simulate the multiphase system more precisely, the thermodynamic free energy of the system has been taken into account by employing the Gibbs free energy function. The behavior of the oxygen bubble through the GDL as a function of the geometrical properties of the GDL was then studied and compared to the experimental results presented by Arbabi et al. (7). Acknowledgements The authors would like to gratefully acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada (NSERC).

IntroductionFor medical and allied health students, knowledge of anatomical variation is important as it may influence physical examination, diagnosis and treatment of patients. Recent studies indicate anatomical variation should be conceptually integrated early into the anatomy curriculum prior to the discipline specific variations taught in surgical and radiological postgraduate training programs. For academic institutions with limited access to cadaveric dissection and anatomy museums, the opportunity for students to appreciate the range of normality in anatomical structures is diminished. Thus, the purpose of this study was to demonstrate how 3D models of anatomical variations may be used to assess structure, function and spatial relationships by incorporating the concept of anatomical variations into assessment paradigms.MethodsTwo 3D digital models depicting upper limb muscular variations, and a 3D teratological model were evaluated by undergraduate kinesiology (KIN) (n = 30), and graduate clinical anatomy (CA) (n = 10) students. The study protocol consisted of the following instruments introduced in sequence: (1) 30‐question Spatial Ability Test (SAT), (2) 16‐question baseline upper limb anatomy test, (3) 13‐question multiple choice quiz based on the displayed 3D models, and (4) Student perception survey (5‐point Likert scale). Based on SAT scores, a median split was used stratify the students into high (KIN: 15, CA: 5) and low spatial ability (KIN: 15, CA: 5). All data are presented as Mean ± SD.ResultsBoth student groups scored similarly on the baseline anatomy knowledge test (KIN: 71 ± 17 %, CA: 71 ± 12%). The mean 3D model quiz scores for KIN students of high spatial ability were 72 ± 16% compared to those of lower spatial ability, 68 ± 14%. The 3D model quiz scores for CA students of high spatial ability were 88 ± 12% compared to CA students of lower spatial ability, 77 ± 15%. The models were perceived as useful in assessing spatial relationships (KIN: 4.4 ± 0.8, CA: 4.9 ± 0.3) and clinical concepts (KIN: 4.0 ± 0.9 CA: 3.9 ± 0.3). Student perceptions were positive for integrating the 3D models into lecture, or laboratory discussions, but KIN students were relatively neutral (3.2 ± 1.2) compared to CA students (3.9 ± 0.3) in their integrated use in bell‐ringer style laboratory assessments. The students expressed interest for a database of explorable 3D models of anatomical variations.ConclusionIntegration of the 3D variant models into anatomy curricula could be a useful means in assessing fundamental anatomical concepts, while demonstrating how deviations in structure can affect normal function. For institutions with computer access but limited cadaveric resources, the 3D models could be powerful supplementary teaching and assessment tools for anatomy students of all education levels and spatial abilities. Furthermore, development of a database of explorable anatomical variations for teaching and learning purposes would be valuable for allied health and medical programs in search of integrating variant anatomy into their anatomy curricula.Support or Funding InformationSupported by: American Association of Anatomists (AAA) Education Research Scholarship; Natural Sciences and Engineering Research Council of Canada (NSERC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Symptoms of insomnia in patients with obstructive sleep apnea: Prevalence, correlates and association with suicidality

Event Abstract Back to Event Modeling membrane-curvature sensing and generation by proteins Michael Birch1 and An-Chang Shi1 1 McMaster University, Physics & Astronomy, Canada Proteins that target cellular membranes with a particular curvature (i.e. curvature sensing proteins), as well as those that change the local membrane-curvature (i.e. curvature generating proteins), appear in a variety of biological processes. For example, the recruitment of proteins between different stages of endocytosis appears to be curvature driven and the proteins also shape the membrane as the vesicle is formed. Moreover, some proteins that interact with membrane-curvature are known to play a role in certain diseases, for example Parkinson's. It has also been observed that certain proteins can both sense and generate curvature under different conditions. We are developing a physical model for the study of membrane-curvature sensing and generation, focusing on the question "What determines whether a protein senses or generates curvature?". The model includes parameters for the bending rigidity of the protein and interaction strength with the membrane. The results of such a model could provide insights into the mechanism of protein-membrane interactions, as well as principles for the design of biomaterials sensing and generating the curvature of cellular membranes. Natural Sciences and Engineering Research Council of Canada (NSERC) Keywords: modeling, protein Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Computational modeling in biomaterials science and engineering Citation: Birch M and Shi A (2016). Modeling membrane-curvature sensing and generation by proteins. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00818 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael Birch An-Chang Shi Google Michael Birch An-Chang Shi Google Scholar Michael Birch An-Chang Shi PubMed Michael Birch An-Chang Shi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Research and development activities on high efficiency separation process technologies for carbon dioxide removal from industrial sources at University of Regina, Canada

Proton Exchange Membrane (PEM) failure is one of the key criteria in deciding the durability of the PEM fuel cell system. Physical properties such as ionic conductivity and mechanical properties depend on the microstructure. The microstructure is itself strongly dependent on the water content of the membrane (1, 2). It is therefore important to fully understand the effect of degradation stressors on the morphological changes and water-uptake characteristics in order to improve membrane durability.In this work, standard perfluorosulfonic acid (PFSA) ionomer membranes are subjected to a combined chemical and mechanical accelerated stress test (AST) used for rapid benchmarking of in-situ membrane stability. The degradation stressors in the combined chemical/mechanical AST was previously shown by our group to change the molecular structure and lead to membrane material loss (3). The chemical phase of the AST generates hydroxyl radicals that attack both the side chain and main chain of the polymer, while the mechanically generated stresses due to humidity cycling accelerate mechanical failures. The observed structural changes are anticipated to alter the water-uptake properties of the membrane, as shown previously for ex-situ testing (4). The degradation also alters the morphology, ion exchange capacity, mechanical properties, and proton conductivity of the membrane (5). Water-uptake measurements of partially AST degraded catalyst coated membrane (CCM) samples are carried out at room temperature using a dynamic vapor sorption system. In spite of severe fluoride release and membrane thinning, the water-uptake per unit mass of the AST degraded CCMs is found to be relatively constant. Since the test specimens are CCMs which contain a significant amount of catalyst layer material, an attempt is made to measure and separate the mass of the ionomer by thermogravimetric analysis (TGA). The ionomer material loss throughout the AST process is significant due to fluoride release and ionomer degradation, up to roughly 50% at end-of-life (3). The water-uptake per unit mass of ionomer in the CCM is determined by extracting the ionomer weight obtained by heating the CCM in the TGA chamber. In contrast to the previous results normalized by specimen dry weight, the water-uptake increases significantly per unit mass of the ionomer in the CCM, as shown in Fig. 1. Although the increased water-uptake may indicate enlarged solvated hydrophilic domains in the membrane, which is good for enhanced proton mobility, the proton conductivity is found to decrease (Fig. 1). This may be attributed to a decay in proton concentration due to sulfonic acid functional group loss during side chain degradation. The overall effects of the combined chemical/mechanical AST on the membrane morphology and properties are presented and compared to provide additional insight into the complex degradation mechanism.ACKNOWLEDGMENTSResearch funding provided by Automotive Partnership Canada (APC), Natural Sciences and Engineering Research Council of Canada (NSERC) and Ballard Power Systems (BPS) is gratefully acknowledged. BPS is also acknowledged for providing access to experimental facilities, material samples and technical support. REFERENCES1. J.Benziger, A. Bocarsly, M. J. Cheah, P. Majsztrik, B. Satterfield, and Q. Zhao, in Fuel Cells and Hydrogen Storage 141, Bocarly and Mingos, Editors, p. 85 Springer, Berlin Heidelberg 141 (2011).2. Y. Yang, A. Siu, T. J. Peckham, S. Holdcroft, in Advances in Polymer Sciences 215: Fuel cells 1, G. G. Scherer, Editor p. 55 Springer, Berlin Heidelberg 215 (2008).3. C. Lim, L. Ghassemzadeh, F. Van Hove, M. Lauritzen, J. Kolodziej, G.G. Wang, S. Holdcroft, E. Kjeang, J. Power Sources 257 102 (2014).4. L. Ghassemzadeh and S. Holdcroft, J.Am.Chem.Soc. 135 8181 (2013).5. S. V. Venkatesan and E. Kjeang, 11th International Fuel Cell Science, Engineering and Technology Conference, ASME, Minneapolis, MN (2013).

Why are some university researchers more likely to create spin-offs than others? Evidence from Canadian universities

Description Mast cells are immune sentinels recognized for their role in allergic inflammation. Allergen-induced FcεRI activation initiates a biphasic response characterized by the rapid degranulation of preformed mediators and the delayed release of cytokines and chemokines. Triacylglycerols (TAG) serve as a source of energy required for cellular functions. Diacylglycerol O-acyltransferase 2 (DGAT2) is an enzyme responsible for the esterification of fatty acids to glycerol during TAG synthesis prior to storage or utilization. Currently, the metabolic requirements of mast cell activation are poorly understood. Therefore, we sought to characterize the importance of TAG as an energy source following allergen activation. IgE-sensitized murine mast cells were treated with the DGAT2 inhibitor JNJ DGAT2-A (JNJ) and stimulated with TNP-BSA and SCF. Following activation, degranulation was measured via β-hexosaminidase release, ELISAs were used to determine cytokine/chemokine release and O2 consumption was measured with a O2k-FluorRespiromoter. Here, DGAT2 inhibition reduced mast cell degranulation (p = 0.02). JNJ treatment significantly reduced the release of IL-6 (p = 0.0002), IL-13 (p = 0.002), TNF (p = 0.0002), CCL1 (p = 0.017) and CCL2 (p = 0.024), independent of any changes to O2 consumption. Together, these results highlight the potential regulatory role of DGAT2 activity during allergen-mediated mast cell activation, making it an intriguing therapeutic target to help combat the allergy epidemic. Funding Sources Canadian Foundation for Innovation (CFI), Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant and Alexandar Graham Bell Canadian Graduate Scholarship (CGS-D), Ontario Government, and Brock University Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)