Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications.

The drug development process can greatly benefit from liver-on-a-chip platforms aiming to recapitulate the physiology, mechanisms, and functionalities of liver cells in an in vitro environment. The liver is the most important organ in drug metabolism investigation. Here, we report the development of a hybrid cyclic olefin copolymer (COC) and polydimethylsiloxane (PDMS) microfluidic (HCP) platform to culture a Huh7 hepatoma cell line in dynamic conditions towards the development of a liver-on-a-chip system. The microfluidic platform is comprised of a COC bottom layer with a microchannel and PDMS-based flat top layer sandwiched together. The HCP device was applied for culturing Huh7 cells grown on a collagen-coated microchannel. A computational fluid dynamics modeling study was conducted for the HCP device design revealing the presence of air volume fraction in the chamber and methods for optimizing experimental handling of the device. The functionality and metabolic activity of perfusion culture were assessed by the secretion rates of albumin, urea, and cell viability visualization. The HCP device hepatic culture remained functional and intact for 24 h, as assessed by resulting levels of biomarkers similar to published studies on other in vitro and 2D cell models. The present results provide a proof-of-concept demonstration of the hybrid COC-PDMS microfluidic chip for successfully culturing a Huh7 hepatoma cell line, thus paving the path towards developing a liver-on-a-chip platform.

CFD Modeling of Chamber Filling in a Micro-Biosensor for Protein Detection.

Tuberculosis (TB) remains one of the main causes of human death around the globe. The mortality rate for patients infected with active TB goes beyond 50% when not diagnosed. Rapid and accurate diagnostics coupled with further prompt treatment of the disease is the cornerstone for controlling TB outbreaks. To reduce this burden, the existing gap between detection and treatment must be addressed, and dedicated diagnostic tools such as biosensors should be developed. A biosensor is a sensing micro-device that consists of a biological sensing element and a transducer part to produce signals in proportion to quantitative information about the binding event. The micro-biosensor cell considered in this investigation is designed to operate based on aptamers as recognition elements against Mycobacterium tuberculosis secreted protein MPT64, combined in a microfluidic-chamber with inlet and outlet connections. The microfluidic cell is a miniaturized platform with valuable advantages such as low cost of analysis with low reagent consumption, reduced sample volume, and shortened processing time with enhanced analytical capability. The main purpose of this study is to assess the flooding characteristics of the encapsulated microfluidic cell of an existing micro-biosensor using Computational Fluid Dynamics (CFD) techniques. The main challenge in the design of the microfluidic cell lies in the extraction of entrained air bubbles, which may remain after the filling process is completed, dramatically affecting the performance of the sensing element. In this work, a CFD model was developed on the platform ANSYS-CFX using the finite volume method to discretize the domain and solving the Navier-Stokes equations for both air and water in a Eulerian framework. Second-order space discretization scheme and second-order Euler Backward time discretization were used in the numerical treatment of the equations. For a given inlet-outlet diameter and dimensions of an in-house built cell chamber, different inlet liquid flow rates were explored to determine an appropriate flow condition to guarantee an effective venting of the air while filling the chamber. The numerical model depicted free surface waves as promoters of air entrainment that ultimately may explain the significant amount of air content in the chamber observed in preliminary tests after the filling process is completed. Results demonstrated that for the present design, against the intuition, the chamber must be filled with liquid at a modest flow rate to minimize free surface waviness during the flooding stage of the chamber.

Geometric Predictors of Abdominal Aortic Aneurysm Maximum Wall Stress.

Abdominal aortic aneurysm (AAA) is a dilation of the abdominal aorta (above 50 % of its original diameter), which can cause death upon rupturing. It usually grows asymptomatically leading to late clinical intervention. The medical criteria to indicate surgery are based on measuring the diameter and growth rate, but in many cases aneurysms fail at uncharacterized critical values. In search of a more efficient technique in predicting AAA failure, there is consensus on the importance of studying its geometric characteristics and estimation of the wall stress, but no fully successful correlation has been found between the two yet. This work examines the relationship between a parameterized geometry (18 input variables and 10 dependent indices) and 1 output variable: the maximum wall stress. Design of Experiments (DOE) techniques are used to generate 183 geometric configurations, for which Finite Element Analyses are performed using ANSYS™ state-of-the-art solver with a hyperelastic, isotropic and homogeneous arterial model for the wall, considering systolic internal pressure (steady state) and the restriction of longitudinal movement at the blood vessel end-sections. Due to the large number of independent parameters to consider, a preliminary Parameters Correlation analysis was performed to determine if a correlation between all input parameters and the maximum stress existed. The correlations between input parameters and the output variable were determined using the Spearman Rank correlation. Correlations with the maximum wall stress for: maximum diameter (ρ = 0.46), wall thickness (ρ = 0.35), dc parameter (ρ = 0.21) and tortuosity (ρ = 0.55) were found. The response surface function between geometry and maximum wall stress was estimated by three models: Universal Kriging geostatistical regression (18 parameters), multiple linear regression (4 parameters) and multiple exponential regression (4 parameters). The models accounted for the stress variance by 99 %, 61 % and 66 %, respectively, with average percentage errors of 0.12 %, 16 % and 17 %, respectively. The solution spaces obtained from this study might provide physicians with a better estimation of the AAA rupture potential and thus, facilitate safer and anticipated treatments of the condition.

Comparison between landfill gas and waste incineration for power generation in Astana, Kazakhstan.

The city of Astana, the capital of Kazakhstan, which has a population of 804,474, and has been experiencing rapid growth over the last 15 years, generates approximately 1.39 kg capita(-1) day(-1) of municipal solid waste (MSW). Nearly 700 tonnes of MSW are collected daily, of which 97% is disposed of at landfills. The newest landfill was built using modern technologies, including a landfill gas (LFG) collection system.The rapid growth of Astana demands more energy on its path to development, and the viability analysis of MSW to generate electricity is imperative. This paper presents a technical-economic pre-feasibility study comparing landfill including LFG utilization and waste incineration (WI) to produce electricity. The performance of LFG with a reciprocating engine and WI with steam turbine power technologies were compared through corresponding greenhouse gases (GHG) reduction, cost of energy production (CEP), benefit-cost ratio (BCR), net present value (NPV) and internal rate of return (IRR) from the analyses. Results demonstrate that in the city of Astana, WI has the potential to reduce more than 200,000 tonnes of GHG per year, while LFG could reduce slightly less than 40,000 tonnes. LFG offers a CEP 5.7% larger than WI, while the latter presents a BCR two times higher than LFG. WI technology analysis depicts a NPV exceeding 280% of the equity, while for LFG, the NPV is less than the equity, which indicates an expected remarkable financial return for the WI technology and a marginal and risky scenario for the LFG technology. Only existing landfill facilities with a LFG collection system in place may turn LFG into a viable project.