Microfabrication Process Development for a Polymer-Based Lab-on-Chip Concept Applied in Attenuated Total Reflection Fourier Transform Infrared Spectroelectrochemistry.

Micro electro-mechanical systems (MEMS) combining sensing and microfluidics functionalities, as are common in Lab-on-Chip (LoC) devices, are increasingly based on polymers. Benefits of polymers include tunable material properties, the possibility of surface functionalization, compatibility with many micro and nano patterning techniques, and optical transparency. Often, additional materials, such as metals, ceramics, or silicon, are needed for functional or auxiliary purposes, e.g., as electrodes. Hybrid patterning and integration of material composites require an increasing range of fabrication approaches, which must often be newly developed or at least adapted and optimized. Here, a microfabrication process concept is developed that allows one to implement attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and electrochemistry on an LoC device. It is designed to spatially resolve chemical sensitivity and selectivity, which are instrumental for the detection of chemical distributions, e.g., during on-flow chemical and biological reaction chemistry. The processing sequence involves (i) direct-write and soft-contact UV lithography in SUEX dry resist and replication in polydimethylsiloxane (PDMS) elastomers as the fluidic structure; (ii) surface functionalization of PDMS with oxygen plasma, 3-aminopropyl-triethoxysilane (APTES), and a UV-curable glue (NOA 73) for bonding the fluidic structure to the substrate; (iii) double-sided patterning of silicon nitride-coated silicon wafers serving as the ATR-FTIR-active internal reflection element (IRE) on one side and the electrode-covered substrate for microfluidics on the back side with lift-off and sputter-based patterning of gold electrodes; and (iv) a custom-designed active vacuum positioning and alignment setup. Fluidic channels of 100 µm height and 600 µm width in 5 mm thick PDMS were fabricated on 2" and 4" demonstrators. Electrochemistry on-chip functionality was demonstrated by cyclic voltammetry (CV) of redox reactions involving iron cyanides in different oxidation states. Further, ATR-FTIR measurements of laminar co-flows of H2O and D2O demonstrated the chemical mapping capabilities of the modular fabrication concept of the LoC devices.

Chemical Imaging of Mass Transport Near the No-Slip Interface of a Microfluidic Device using Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy.

Mass transport in geometrically confined environments is fundamental to microfluidic applications. Measuring the distribution of chemical species on flow requires the use of spatially resolved analytical tools compatible with microfluidic materials and designs. Here, the implementation of an attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) imaging (macro-ATR) approach for chemical mapping of species in microfluidic devices is described. The imaging method is configurable between a large field of view, single-frame imaging, and the use of image stitching to build composite chemical maps. Macro-ATR is used to quantify transverse diffusion in the laminar streams of coflowing fluids in dedicated microfluidic test devices. It is demonstrated that the ATR evanescent wave, which primarily probes the fluid within ∼500 nm of the channel surface, provides accurate quantification of the spatial distribution of species in the entire microfluidic device cross section. This is the case when flow and channel conditions promote vertical concentration contours in the channel as verified by three-dimensional numeric simulations of mass transport. Furthermore, the validity of treating the mass transport problem in a simplified and faster approach using reduced dimensionality numeric simulations is described. Simplified one-dimensional simulations, for the specific parameters used herein, overestimate diffusion coefficients by a factor of approximately 2, whereas full three-dimensional simulations accurately agree with experimental results.

Scanning Aperture Approach for Spatially Selective ATR-FTIR Spectroscopy: Application to Microfluidics.

We present a novel spectroscopy accessory that can easily convert any Fourier transform infrared (FTIR) spectrometer into a fully automated mapping and assaying system. The accessory uses a multiridge attenuated total reflection (ATR) wafer as the sensing element coupled with a moving aperture that is used to select the regions of interest on the wafer. In this demonstration, the accessory is combined with a series of parallel micropatterned channels, which are positioned co-linear with the light-coupling ridges on the opposite side of the ATR wafer. The ATR spectroscopy microfluidic assay accessory (ASMAA) was used in continuous mapping mode to scan perpendicular to the ATR ridges, revealing complex but repeatable oscillations in the spectral intensities. To understand this behavior, the light path through the optical components was simulated with consideration of the aperture position, ridge-to-channel alignment, and excitation beam profile. With this approach, the simulation reproduced the experimental mapping results and provided evidence that the measurement position and area changed with the aperture position. To demonstrate the assay mode, we obtained spectra along the centerline of individual microchannels and determined noise baselines and limits of detection.

Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane.

The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Here, we present a lung-on-a-chip, based on a biological, stretchable and biodegradable membrane made of collagen and elastin, that emulates an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms PDMS in many ways: it does not absorb rhodamine-B, is biodegradable, is created by a simple method, and can easily be tuned to modify its thickness, composition and stiffness. The air-blood barrier is reconstituted using primary lung alveolar epithelial cells from patients and primary lung endothelial cells. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks.

Microfluidic devices for the detection of viruses: aspects of emergency fabrication during the COVID-19 pandemic and other outbreaks.

Extensive testing of populations against COVID-19 has been suggested as a game-changer quest to control the spread of this contagious disease and to avoid further disruption in our social, healthcare and economical systems. Nonetheless, testing millions of people for a new virus brings about quite a few challenges. The development of effective tests for the new coronavirus has become a worldwide task that relies on recent discoveries and lessons learned from past outbreaks. In this work, we review the most recent publications on microfluidics devices for the detection of viruses. The topics of discussion include different detection approaches, methods of signalling and fabrication techniques. Besides the miniaturization of traditional benchtop detection assays, approaches such as electrochemical analyses, field-effect transistors and resistive pulse sensors are considered. For emergency fabrication of quick test kits, the local capabilities must be evaluated, and the joint work of universities, industries, and governments seems to be an unequivocal necessity.

Numerical Modelling of a Nanopore-based Resistive-Pulse Sensor for Detection of Biomolecules.

Resistive pulse sensors (RPS) are based on the detection principle of partial and non-permanent obstruction of an electrically conducting channel. The integration of RPS in microfluidics has the potential for detections at the molecular level. Current challenges involve limitations in fabrication technology, most notably the finite structure accuracy and fabrication repeatability, which have a direct and strong impact on RPS device performance. In this work, we analyzed the geometrical structure and performance of a nanofabricated RPS device and iteratively used the experimental data to propose an adequate numerical model which also accounts for fabrication imperfections beyond the optical resolution limit. The proposed model for a nano-RPS was validated and able to augment the understating of the structure and operation of a microdevice.Clinical Relevance- This work is part of a greater effort to bring microfluidics devices closer to patients for bedside analysis of blood, or other human fluids, for instance. These devices can potentially perform screening for multiple targets in one sample. New devices often need to go through design, prototyping and bench tests, simulation models as the one presented can increase the chances of the device to get to the market in reduced time.

SyLMAND: a microfabrication beamline with wide spectral and beam power tuning range at the Canadian Light Source.

SyLMAND, the Synchrotron Laboratory for Micro and Nano Devices, is a recently commissioned microfabrication bend magnet beamline with ancillary cleanroom facilities at the Canadian Light Source. The synchrotron radiation is applied to pattern high-aspect-ratio polymer microstructures used in the area of micro-electro-mechanical systems (MEMS). SyLMAND particularly focuses on spectral and beam power adjustability and large exposable area formats in an inert gas atmosphere; a rotating-disk intensity chopper allows for independent beam-power reduction, while continuous spectral tuning between 1-2 keV and >15 keV photon energies is achieved using a double-mirror system and low-atomic-number filters. Homogeneous exposure of samples up to six inches in diameter is performed in the experimental endstation, a vertically scanning precision stage (scanner) with tilt and rotation capabilities under 100 mbar helium. Commissioning was completed in late 2017, and SyLMAND is currently ramping up its user program, mostly in the areas of RF MEMS, micro-fluidics/life sciences and micro-optics.

Polymer-based X-ray masks patterned by direct laser writing.

X-ray masks are indispensable tools in deep X-ray lithography (XRL). To date, hardly any fabrication technology can provide affordable and readily available masks with good structure quality. The bottleneck of adequate masks to a large extent limits the widespread use of XRL. In this article, an alternative XRL mask fabrication process is described to significantly improve availability and cost efficiency of XRL masks as key instruments in XRL processing: A 355 nm UV-laser is applied to expose SU-8 resist on an antireflective coating and a copper sacrificial substrate. The voids in this resist template are filled by a two-step electroplating process with sacrificial nickel and 3.6 µm thick gold absorbers. A second SU-8 coat embeds the absorbers, forming the 40 µm mask membrane. This configuration allows for XRL into resists of up to about 200 µm thickness at the SyLMAND beamline, Canada. The absorber structure accuracy is about 1 µm, at smallest tested lateral dimensions of 2 µm isolated features and 500 nm details. Upon release from the substrate, the membrane locally deforms by up to 1.79 µm. PMMA microstructures patterned with such a mask have smooth and vertical sidewalls. The SyLMAND chopper allows one to limit thermal deformations during exposure to the micrometer range: At a beam power of 0.42 W, typical thermal deformations are 0.5 µm-1.4 µm, depending on the layout, and position inaccuracies are about 3.3 µm.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectromicroscopy Using Synchrotron Radiation and Micromachined Silicon Wafers for Microfluidic Applications.

A custom-designed optical configuration compatible with the use of micromachined multigroove internal reflection elements (µ-groove IREs) for attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy and imaging applications in microfluidic devices is described. The µ-groove IREs consist of several face-angled grooves etched into a single, monolithic silicon chip. The optical configuration permits individual grooves to be addressed by focusing synchrotron sourced IR light through a 150 µm pinhole aperture, restricting the beam spot size to a dimension smaller than that of the groove walls. The effective beam spot diameter at the ATR sampling plane is determined through deconvolution of the measured detector response and found to be 70 µm. The µ-groove IREs are highly compatible with standard photolithographic techniques as demonstrated by printing a 400 µm wide channel in an SU-8 film spin-coated on the IRE surface. Attenuated total reflection FT-IR mapping as a function of sample position across the channel illustrates the potential application of this approach for rapid prototyping of microfluidic devices.

Characterization of the surface contamination of deep X-ray lithography mirrors exposed to synchrotron radiation.

In deep X-ray lithography (DXRL), synchrotron radiation is applied to pattern polymer microstructures. At the Synchrotron Laboratory for Micro and Nano Devices (SyLMAND), Canadian Light Source, a chromium-coated grazing-incidence X-ray double-mirror system is applied as a tunable low-pass filter. In a systematic study, the surface conditions of the two mirrors are analyzed to determine the mirror reflectivity for DXRL process optimization, without the need for spectral analysis or surface probing: PMMA resist foils were homogeneously exposed and developed to determine development rates for mirror angles between 6 mrad and 12 mrad as well as for white light in the absence of the mirrors. Development rates cover almost five orders of magnitude for nominal exposure dose (deposited energy per volume) values of 1 kJ cm-3 to 6 kJ cm-3. The rates vary from case to case, indicating that the actual mirror reflectivity deviates from that of clean chromium assumed for the experiments. Fitting the mirror-based development rates to the white-light case as a reference, reflectivity correction factors are identified, and verified by experimental and numerical results of beam calorimetry. The correction factors are related to possible combinations of a varied chromium density, chromium oxidation and a carbon contamination layer. The best fit for all angles is obtained assuming 7.19 g cm-3 nominal chromium density, 0.5 nm roughness for all involved layers, and an oxide layer thickness of 25 nm with a carbon top coat of 50 nm to 100 nm. A simulation tool for DXRL exposure parameters was developed to verify that the development rates for all cases do coincide within a small error margin (achieving a reduction of the observed errors by more than two orders of magnitude) if the identified mirror surface conditions are considered when calculating the exposure dose.