This PDF file contains the front matter associated with SPIE Proceedings Volume 11955 including the Title Page, Copyright information, and Table of Contents.

This paper presents a novel, lightweight, integrated, and wearable sensor for real-time and multiplexed monitoring of biomarkers in sweat. We report a wearable skin patch made with a benchtop craft cutter, thereby resulting in low-cost, roll-to-roll, and cleanroom-free fabrication. The integrated device is wearable on the arm like a small flexible bandage that is comprised of a microfluidic channel and a dual-modality transducer. The microfluidic channel ensures fast, continuous, and reproducible sweat transport from the skin to the sensors while minimizing the evaporation and contamination of sweat droplets. The transducer generates both electrochemical and fiber-optic based localized surface plasmon resonance (LSPR) signals on a single chip. Furthermore, sweat collection is noninvasive compared to other body fluids (e.g., blood, urine, or saliva), correlates well with blood biomarker levels, and bypasses diurnal rhythm challenges. Elevated levels of cytokines, including interleukin-6 (IL-6), predict chronic diseases including diabetes, heart disease, and therapeutic responses in fatigue, pain, and depression. The electrochemical sensor measures the IL-6 levels with a high sensitivity of 122.59 μA (pg/mL) ^-1 cm^-2 and a limit of detection (LoD) of 0.886 fg/mL. The fiber-optic sensor exhibits LSPR shifts in response to varying IL-6 levels with a sensitivity of 0.87 % Log(ng/ml)^-1 and LoD of 1.48 ng/ml. Our integrated sensor has the potential to overcome the challenges associated with the current infection/inflammation screening technology by detecting a low concentration of inflammatory biomarkers in sweat that is rich in physiological and metabolic information, providing multiplexed monitoring on a single chip, and utilizing a simple screen-printing technique for large-scale fabrication. This integrated sensor holds the potential to provide real-time feedback on the infection progression and allow on-demand drug delivery.

Conductive hearing loss (CHL) is the most common type of hearing impairment among infants and young children. Most conductive hearing aids, including bone-anchored aids, are invasive and require surgical procedures to be implanted into the skull. In addition, non-invasive wearable conductive hearing aids are bulky, rigid, and unstable. Neither aid is ideal for infants and pediatric patients with conductive hearing loss. Here, we implemented a unimorph piezoelectric actuator into a flexible substrate to achieve a micro-epidermal actuator for non-invasive Band-Aid-like conductive hearing aids. The flexible aid will generate vibrations on the surface of skin and transmit to the cochlea through a skin-bone path, thus bypassing obstructions and damage in the auditory canal. We used finite element analysis to study vibrations from microepidermal actuators and obtain output force level. A Laser Doppler vibrometer was also used to measure displacement of vibrations for an actuator placed on a segment of a cadaveric skull calvarium.

Miniaturized micro-electro-mechanical systems (MEMS) loudspeakers is a current developmental trend for in-ear audio applications. However, when a loudspeaker shrinks to a size of a microelectronic chip, the involved physics starts to differ from the macroscopic world. At one side, an electrostatic µSpeakers benefits from small electrode gaps leading to high driving forces. At the same time, the fluid dynamics of the air can cause strong damping forces inside the microscopic cavities of a MEMS loudspeakers chip. Recently we have shown experimentally that the first Euler-Bernoulli bending mode is sufficient to reproduce the behavior of a Coulomb-actuated microbeam over the entire stroke with high accuracy. This leads to an ab initio modeling approach based on a novel Chebyshev-Edgeworth type expansion that leads to an accurate lumped parameter model (LPM) with a single degree of freedom for MEMS loudspeakers. In this work, we discuss the influence of microfluidics on the damping of a balanced nanoscopic electrostatic drive (NED) test loudspeaker design. With the help of the finite element method (FEM) we analyze how the pressure and velocity distribution is linked to the Euler-Bernoulli modes of a simple micro-beam, with the aim of including the squeeze film damping in the LPM. Understanding the various sources of fluid dynamic damping is of great importance for the design of high fidelity MEMS based electrostatic audio transducers (μSpeakers).

Calorimetry is a label-free technique that can provide valuable insight into the thermodynamics of drug binding important to drug design and development. Nonetheless, conventional isothermal titration calorimetry is not used in highthroughput drug screening campaigns due to its high sample consumption and limited throughput. In previous work, we demonstrated an optical analog that involves measurements of the spectral reflectance of thermochromic liquid crystal (TLC) particles, and employs microfluidics to enable rapid measurement of reaction enthalpy in sub-nanoliter aqueous droplets. To optimize system performance, we have evaluated mixing of reactants in droplets with a custom-fabricated microfluidic chip. In addition, we constructed a large area illuminator and dichroic detection blocks to scale to multiple detection points along the droplet travel direction to probe the droplet temperature at several time points. Our platform’s current temperature resolution of 3 mK is on the same order as commercial ITCs and 10-fold better than most nanocalorimeters. This label-free microfluidic calorimeter with scalable optical read-out has the potential to accelerate the process of drug discovery in high-throughput screening campaigns.

Epigenetics, the study of inheritable mechanisms that regulate gene expression, has clinical ramifications from cancer to autoimmune disorders to psychiatric pathologies. The main tool to study epigenetics is chromatin immunoprecipitation (ChIP), which probes the relationship between DNA and its structural nucleosome-forming histone proteins. Standard benchtop ChIP has three major drawbacks: (1) it requires a large input volume of cells, (2) it is very time consuming and work intensive, and (3) it is low throughput. Digital microfluidic biochips (DMFB) have proven to be successful at utilizing small volumes of reagents and samples to perform high throughput bioanalyses and assays of macromolecules. Their ease of configurability, automation, and high sensitivity make them an ideal platform for ChIP adaptation. Previously, we demonstrated the first step towards ChIP implementation on a DMFB by detecting specifically modified nucleosomes, the building blocks of chromatin, in a semi-quantitative nucleosome immunoprecipitation (NuIP) assay. Herein, we modify the prior ‘sweep-through’ DMFB design to enhance the capture and detection of analyte-bound magnetic beads. With this modification, we can increase both the level of detection and granularity when probing a sample. Furthermore, this new ‘pull-through’ design presents a novel method for bead collection using an on-chip magnetic source.

Carbon dioxide capture and storage into underground geological formations is a promising route to reduce emissions into the atmosphere and limit global warming. Geo-sequestration involves the injection of carbon laden solutions directly into the pore space in sedimentary rocks, saline formations, or abandoned oil fields. More scientific research is still needed to understand how the pore structure and material properties of the rock matrix influence the extent to which pressurized fluids can be injected and permeate the pore network. Our research focuses on studying the fundamental mechanics of pore infiltration at micro- and nanoscopic scales to develop a comprehensive model of carbon dioxide sequestration within geological pore networks. We are using single and two-phase flow simulations of fluid injection into the rock pore space, modeled as a network of capillaries representing the geometry extracted from high-resolution X-ray microtomography of suitable rocks. To experimentally validate the simulation results, we have developed a Si/SiO2 lab-on-chip platform for testing porosity models on well-defined geometries at the microscale. The single and multiphase flow measurements performed on the microfluidic chip are monitored with optical microscopy in real time. In this contribution, we will report the progress in our research and development of optical imaging techniques applied to the microfluidic chip. Specifically, we demonstrate how advanced image analysis can be used to extract information about the flow properties. The image analysis results are critical for calibrating high-accuracy flow simulation models for pore scale injection and mineralization of carbon dioxide. The rock-on-chip platform is used also to measure chemical and physical processes governing the carbonate precipitation step of CO2 mineralization. The reaction of CO2 in the microfluidic channels can be detected through crystal formation over time. Fluorescence microscopy and Raman-spectroscopy is used to monitor carbonate precipitation rates directly on chip, to map minerals and track reaction kinetics under different conditions.

A virus can cause various serious diseases, some of which could destroy entire countries geographically and economically by sweeping infections that were resistant to established treatment. In an attempt to fight a virus, the immune system produces antibodies (IgM/IgG proteins), and the presence of these antibodies is linked to the presence of the infection in the patient. Detecting and measuring the presence of these antibodies would be incredibly valuable for population control and surveillance. However, developing an automated microfluidic immunoassay testing device typically requires a complicated and time-consuming robotic fluid handling technique, which is both expensive and impractical for point-of-care testing. In this study, we demonstrate an integrated microfluidic system, where sample mixing, loading, and detection can be conducted automatically by a smartphone device. Furthermore, we design a 3D printed sample cartridge module, where only 25 μL of a blood sample can be collected to perform the antibody detection test. Additionally, as a feasibility study, we demonstrate sample mixing and detection performance of our device, where the sample mixing is conducted by bidirectional rotation, and the detection efficiency is evaluated by confining cells within a focal plane by rotating the sample cartridge at high speed.

A 3D printed microfluidic device for Caenorhabditis elegans analysis. The biocompatibility of the 3D printed poly(ethylene glycol) diacrylate hydrogel resin was conducted and had no observable effect on worm lifespans. Worm organ morphology was directly observable through the microfluidic device and low autofluorescence was demonstrated using genetically-modified pharynx fluorescent worms.

Dairy milk composition analysis is critical for quality control and pricing purposes. Particularly, fat content in dairy milk determines its market value, and free fatty acids can be used as a proxy for milk quality. Milk with high fat contents (4% and above) is progressively skimmed to obtain a chain of products (butter, cheese, milk, powder milk, etc.), increasing the profitability in a traditionally low-margin industry. Besides total fat percentage, the composition of fatty acids is also relevant, as C14, C16 and C18 free fatty acids can be used to monitor cattle food intake. Established chemical separation techniques to measure fat content, such as the Gerber method, are off-line, manual, labor intensive, cannot distinguish fats and have a high error margin. We present a monitoring system concept, free of labelling and sample processing, for fat milk content using Raman spectroscopy in flowing microfluidic channels. The technique has been tested using several microfluidic flow rates (20 μl/min to 1000 μl/min) with Raman measurements of 5 seconds of exposure time and with a single accumulation. We show that Raman spectra remain the same even after continuously refreshing the fluid during measurements at increasing flow rates. Proof of concept Raman measurements at the region of interest for undiluted whole (3.5% of fat), semi-skimmed (1.5%) and buttermilk (0.5%) are presented under different microfluidic flows, showing the potential of the technique. The technique can also be used to identify different fats, proteins, and minerals.

Micro systems are an indispensable tool in many research areas. Their applications range from point-of-care diagnostics to drug development and personalized medicine. Hence multilayer technology is already established in modern printed circuit board manufacturing it could also enable the rapid and effective production of complex microfluidic micro systems, hence it is already cost effective for small batch sizes of 50 pieces and less. By micromachining polymer foils and subsequent thermal bonding, channels and cavities can be realized down to a minimum structure size of 50 µm. For smaller structures, free-standing structures (pillars) or structures with varying depths (e.g. micro lenses), the technology reaches its limits. Such structures can be realized by hot embossing. Nevertheless, some challenges still remain when multilayer manufacturing and hot embossing technology are combined: First the filigree, hot embossed structures must be retained during the subsequent joining processes. Second the hot embossed components are usually very thin and significantly smaller than the overall system. Successful integration requires exact positioning and handling without twisting. Here we present the realization of multilayer based micro-fluidic systems for the integration of hot embossed components. In this process, joining partners are functionalized using plasma treatment and then bonded at lower pressures and temperatures. For automated assembly, a robot-setup was adapted and customized tools were developed. A special suction gripper even enables the handling of porous membranes without warping. With the extended technology chain, smaller and freestanding structures with varying depths can be realized.

Due to high optical transparency combined with high thermal and chemical stability transparent fused silica glass is of high interest for many applications in microsystems engineering, especially in the field of microfluidics and micro optics. However, structuring of fused silica is inherently difficult and usually includes high temperatures, complicated and toxic etching processes or time consuming grinding protocols with severe limitation to freedom of design and manufacturing speed. Thus, complex structured fused silica glass has been limited especially on the industrial scale. We developed highly filled, thermoplastic fused silica nanocomposites (so-called Glassomers), that can be processed using commonly available high-throughput polymer manufacturing technologies such as injection molding or continuous extrusion. After the shaping process the thermoplastic Glassomer is converted to pure, transparent glass by subsequent debinding and sintering yielding high-quality fused silica glass with high optical transparency (transmission >90 %) and optical surface quality (R_q < 5 nm). We show injection molding of high-resolution microstructures as well as complex shaped macroscopic components that are subsequently converted to pure fused silica glass enabling for the first time mass-market manufacturing of fused silica glass components, enabling a plethora of applications in micro optics and lab-on-a-chip devices.

Microstructured platinum (Pt) is of great importance in a variety of applications from electronics, sensors, microelectromechanical systems, Lab-on-a-Chip devices as well as medical implants such as the cochlear implant. The high electrical conductivity, high melting point, chemical resilience, high catalytic activity, and biocompatibility make Pt the material of choice in these applications. However, microstructuring of Pt and especially 3D microstructuring is challenging and mostly done using vapour-based techniques, which are restricted in the achievable designs or by novel 3D shaping methods, which are limited in terms of processing speed as well as purity and conductivity of the resulting platinum. We developed a platinum containing photoresin, which can be structured via direct lithography and two-photon polymerization. The resulting exposed platinum photoresin objects are subsequently converted to highly conductive and high purity platinum via thermal debinding and reduction. With the direct lithography method, we show that 2.5- dimensional microstructures, such as electrowetting on dielectric devices can be manufactured. By using two-photon polymerization, we show that complex 3D micro and nanoobjects can be fabricated paving the way for novel applications like metamaterials or catalysis as well as biomedical applications, where high surface areas and the physicochemical properties of Pt are highly desirable. By using lithography and two-photon lithography (TPL), we are able to obtain 2.5- dimensional Pt electrode patterns with a layer thickness of 35 nm and an electrical conductivity of 6.32 × 10⁶ S m^-1 as well as complex 3D Pt objects with a resolution of 2 μm and nanopillars of 700 nm, respectively.

Needles are a key, and very common, component of modern medicine, used primarily for drug delivery and blood withdrawals. There are, however, many drawbacks to their use, such as insertion pain, tissue damage, and the development of fears and avoidance of medical care, especially in younger patients. Needle phobia (extreme fear of needles associated with avoidance) affects 1 in 10 people, who are then likely to avoid seeking any medical care. In addition, there are significant populations living with medical conditions, such as diabetes, that require multiple daily injections for effective management of their chronic health condition. Microneedles are small needles less than 1 mm in length that penetrate the skin with minimal or no pain. Microneedles can also reduce tissue damage that can lead to scarification and localized drug resistance in high frequency injection sites. By using high accuracy automated microfabrication techniques, we have developed a new method of quickly and effectively making microneedle arrays capable of interfacing with existing technologies, such as insulin pens and traditional syringes. This work shows a microneedle system which is inexpensive to mass fabricate and preliminary results point to minimal patient pain compared to other microneedle devices. The microneedle construction from a thin metal wire means there is minimal risk of fracture and deposition of material in the dermis that traditional polymeric or silicon microneedles face. This work presents the basis for a pain free injection system that will have significant impacts on patient health, both physical and mental, and healthcare system costs.