The potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries

Idiopathic pulmonary fibrosis (IPF) remains a major clinical challenge to date. Repeated alveolar epithelial microinjuries are considered as the starting point and the key event in both the development and the progression of IPF. Various pro-fibrotic agents have been identified and shown to cause alveolar damage. In IPF, however, no leading cause of alveolar epithelial microinjuries can be identified and the exact etiology remains elusive. New results from epidemiologic studies suggest a causal relation between IPF and frequent episodes of gastric refluxes resulting in gastric microaspirations into the lung. The effect of gastric contents on the alveolar epithelium has not been investigated in detail. Here, we present a microfluidic lung epithelial wounding system that allows for the selective exposure of alveolar epithelial cells to gastric contents. The system is revealed to be robust and highly reproducible. The thereby created epithelial microwounds are of tiny dimensions and best possibly reproduce alveolar damage in the lung. We further demonstrate that exposure to gastric contents, namely hydrochloric acid (HCl) and pepsin, directly damages the alveolar epithelium. Together, this novel in vitro wounding system allows for the creation of in vivo-like alveolar microinjuries with the potential to study lung injury and alveolar wound repair in vitro.

Towards personalized medicine: Chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform

Cancer is responsible for millions of deaths worldwide and the variability in disease patterns calls for patient-specific treatment. Therefore, personalized treatment is expected to become a daily routine in prospective clinical tests. In addition to genetic mutation analysis, predictive chemosensitive assays using patient's cells will be carried out as a decision making tool. However, prior to their widespread application in clinics, several challenges linked to the establishment of such assays need to be addressed. To best predict the drug response in a patient, the cellular environment needs to resemble that of the tumor. Furthermore, the formation of homogeneous replicates from a scarce amount of patient's cells is essential to compare the responses under various conditions (compound and concentration). Here, we present a microfluidic device for homogeneous spheroid formation in eight replicates in a perfused microenvironment. Spheroid replicates from either a cell line or primary cells from adenocarcinoma patients were successfully created. To further mimic the tumor microenvironment, spheroid co-culture of primary lung cancer epithelial cells and primary pericytes were tested. A higher chemoresistance in primary co-culture spheroids compared to primary monoculture spheroids was found when both were constantly perfused with cisplatin. This result is thought to be due to the barrier created by the pericytes around the tumor spheroids. Thus, this device can be used for additional chemosensitivity assays (e.g. sequential treatment) of patient material to further approach the personalized oncology field.

Microfabrication processes for microfluidic devices on a single laser Workstation: direct writing lithography on SU-8, laser ablation on polymers and mask manufacturing

We demonstrate the capability of a laser micromachining workstation for cost-effective manufacturing of a variety of microfluidic devices, including SU-8 microchannels on silicon wafers and 3D complex structures made on polyimide Kapton® or poly carbonate (PC). The workstation combines a KrF excimer laser at 248 nm and a Nd3+:YVO4 DPSS with a frequency tripled at 355 nm with a lens magnification 10X, both lasers working at a pulsed regime with nanoseconds (ns) pulse duration. Workstation also includes a high-resolution motorized XYZ-tilt axis (~ 1 um / axis) and a Through The Lens (TTL) imaging system for a high accurate positioning over a 120 x 120 mm working area. We have surveyed different fabrication techniques: direct writing lithography,mask manufacturing for contact lithography and polymer laser ablation for complex 3D devices, achieving width channels down to 13μ m on 50μ m SU-8 thickness using direct writing lithography, and width channels of 40 μm for polyimide on SiO2 plate. Finally, we have tested the use of some devices for capillary chips measuring the flow speed for liquids with different viscosities. As a result, we have characterized the presence of liquid in the channel by interferometric microscopy.

Using three-dimensional microfluidic networks for solving computationally hard problems

This paper describes the design of a parallel algorithm that uses moving fluids in a three-dimensional microfluidic system to solve a nondeterministically polynomial complete problem (the maximal clique problem) in polynomial time. This algorithm relies on (i) parallel fabrication of the microfluidic system, (ii) parallel searching of all potential solutions by using fluid flow, and (iii) parallel optical readout of all solutions. This algorithm was implemented to solve the maximal clique problem for a simple graph with six vertices. The successful implementation of this algorithm to compute solutions for small-size graphs with fluids in microchannels is not useful, per se, but does suggest broader application for microfluidics in computation and control.

A new microfluidic methodology to assess the haemocompatibility of magnetic nanoparticles designed for theranostic applications

The remarkable physicochemical properties of magnetic nanoparticles (MNPs) at the nanoscale have boosted the development of new and promising strategies for the simultaneous diagnosis and treatment of diseases, particularly in cancer therapy Ð the so-called theranostic applications (1). In these strategies, the intrinsic superparamagnetic properties of MNPs have been exploited to gain access into multifunctional systems able to simultaneously perform as enhanced magnetic resonance imaging (MRI) contrast agents, efficient nanocarriers for drug delivery and nanoheaters in magnetic hyperthermia based therapy (2), among others.

Improving the Manufacturability of Active Microfluidic Devices using Stereolithography (SL)

Thesis (Master's)--University of Washington, 2016-06

Compact tunable microfluidic interferometer

We demonstrate a compact tunable filter based on a novel microfluidic single beam Mach-Zehnder interferometer. The optical path difference occurs during propagation across a fluid-air interface ( meniscus), the inherent mobility of which provides tunability. Optical losses are minimized by optimizing the meniscus shape through surface treatment. Optical spectra are compared to a 3D beam propagation method simulations and good agreement is found. Tunability, low insertion loss and strength of the resonance are well reproduced. The device performance displays a resonance depth of - 28 dB and insertion loss maintained at - 4 dB. (C) 2004 Optical Society of America.

Microfluidic interferometer

We present a class of compact, fluid-based, interferometric, tunable optical components: the single-beam microfluidic Mach-Zender interferometer. Phase delay is achieved through light propagation across a fluid-air interface (meniscus). The effect of meniscus curvature on the device transmission is considered using the three-dimensional beam propagation method and shown to be an important device parameter. We engineer the meniscus curvature using monomer surface chemistry, rendering it flat, and find that the experimental response corresponds well with simulation. The device has a resonance at 1.3 mum with a 25 dB extinction ratio; the latter can be adjusted by shifting the meniscus position.

A parametric study of droplet deformation through a microfluidic contraction: Low viscosity Newtonian droplets

Numerical simulations are conducted to investigate how a droplet of Newtonian liquid. entrained in a higher viscosity Newtonian liquid, behaves when passing through an axisymmetric microfluidic contraction. Simulations are performed using a transient Volume of Fluid finite volume algorithm, and cover ranges of Reynolds and Weber numbers relevant to microfluidic flows. Results are presented for a droplet to surrounding fluid viscosity ratio of 0.001. In contrast to behaviour at higher viscosity ratios obtained previously by the authors, shear and interfacial tension driven instabilities often develop along the droplet Surface. leading to complex shape development, and in some instances, droplet breakup. (c) 2006 Elsevier Ltd. All rights reserved.

Fabrication of high aspect ratio microfluidic devices using direct FS ablation

We present a single stage direct fs ablation results which show that it is possible to make high quality and high aspect ratio devices in a single stage process using a CAD optimised approach.

Side-detection of out-coupled core light from a microfluidic fiber microslit

The interactions of the core-propagating light with an intersecting microslit within a conventional single-mode fiber are investigated. Orientation-dependent out-coupling of core light was utilized to create side-detection, miniature fiber rotation sensors.