This PDF file contains the front matter associated with SPIE Proceedings Volume 12837, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

On-chip detection of flow rates in microfluidics is critical to lab-on-chip technology. Thermal sensing techniques although widely used are limited by temperature rise of the fluid and issues involving integration inside a microchannel. Electrochemical methods present a reliable alternative. Among the widely used electrochemical techniques, Coulometry measures the charge consumed in a redox reaction at electrode surface. In present work, constant potential coulometry at 2V was performed using an electrochemical workstation on Titanium-Platinum microelectrodes (micropatterned on Si wafer substrate) submerged in a moving 0.1 M NaCl electrolyte solution. The sensing platform consists of Si wafer plasma bonded to a PDMS (poly-dimethyl siloxane) microchannel on top of the electrodes. For a constant applied voltage, the rate of decay of current with time is observed to be a function of the flow rate (flux of ions per unit time). As the flow rate increased, the ions available at the electrode surface increased per unit time leading to slower decay rates. The model equation for current-time curve was obtained as I = αe-(t/τ); where α = 0.0002 ± (1% of 0.0002) and τ = 0.312 to 0.797 for electrolyte (0.1 M NaCl) flow rates ranging from 0 to 200 μL/min. The sensitivity and 3σ resolution of the flow sensor are 0.10 sec/(μL/min)/mm2 and 3.64 μL/min respectively. This work models the coulometric current-time curve as a first order decay problem.

Fear of needles is prevalent, estimated at around 10% in adults worldwide. We report on new solid microneedle arrays made of gold in combination with micro holes to replace traditional hypodermic needles for drug delivery. This work provides a breakthrough for painless drug delivery with precise control over the microneedle width, height, array density and position. Results show successful delivery of liquids through a parafilm layer representing the stratum corneum of the human skin.

Flexible hearing aids can benefit from piezoelectric actuators to generate vibrations on epidermis layer of skin behind the ear and noninvasively bypass conductive hearing loss. However, the major challenge is to generate a strong level of vibrations on the surface of skin that can reach cochlea with thin and low-power actuators. Lead zirconium titanate has a high piezoelectric constant and can generate vibrations with elevated levels of force and acceleration. In this paper, we assembled arrays of unimorph piezoelectric actuators composed of lead zirconium titanate to increase the vibration level and overcome damping in flexible substrate, skin, and bone. Finite element analysis was conducted to study the vibrations from a single actuator as well as an array of actuators. Also, the experimental data showed that an array of two actuators with adjusted phase increased the velocity of vibrations by 18 dB at 9 kHz compared to a single actuator on a flat aluminum foundation.

When a microparticle is exposed to an alternating current (AC) electric field, the polarized particle is moved by the interaction between the dipoles and the AC electric field under dielectrophoresis (DEP). The DEP force is widely used for manipulation of microparticles in diverse practical applications such as 3D manipulation, sorting, transfer, and separation of various particles such as living cells. In this study, we propose integration of surface-enhanced Raman spectroscopy (SERS), an extremely sensitive and versatile technique based on Raman scattering of molecules supported by nanostructured materials, with DEP using a microfluidic device, i.e., the microfluidic device combines metal nanostructures and microelectrodes to characterize electrophysiological and biochemical properties of biological cells. The movement of particles, which varies depending on the electrical properties such as conductivity and permittivity of particles, can be manipulated by the cross-frequency change, which is one of the DEP properties. Raman spectroscopy using this DEP-SERS integrated system can be performed with an improved signal-to-noise ratio by determining the direction of the DEP force applied to the cells with respect to the applied AC power and collecting them on the nanostructure.

Traditionally, kilogram-scale iron (and its alloys) particles can be synthesized by atomizing molten iron. These atomized particles typically follow a log-normal distribution, with a particle size distribution (PSD) usually ranging from a few microns to hundreds of microns. In other words, there is a wide distribution of particle size. In this study, we propose a separation method by passing a solution containing magnetic particles through microfluidic channel within a strong magnetic field. Due to the different magnetic drag forces for different Fe particle sizes, micron-sized Fe particles with almost a single diameter can be separated. This method allows low-cost production of biocompatible single-sized iron particles that can be used as the inner core of core-shell magnetic particles for various applications such as: biofunctionalized colloidal coating for biosensing, biology, and medicine applications. Previous reports from our group showed iron particles by conventional sieving methods in the size range of 1–7 μm [1,2]. The validation experimental setup used in this study included a syringe pμmp, a microfluidic micro-fluidic channel, and a digital microscope [2]. The solution is extruded from the syringe through the syringe pμmp, flows through the catheter to the microfluidic channel on top of a magnetic source. A digital microscope is used to record images on the specific XZ plane from the Y-axis. Through experimental studies, optimized parameters including PSD variation, solution viscosity, separation efficiency, magnetic field intensity and distribution, etc. are reported. Preliminary in vivo biocompatibility testing results of these iron particles will also be reported.

We report the ability of three-dimensional (3D) printing from pure fluorescent protein in the colors red, blue and green via femtosecond laser direct write (fs-LDW) technology. We utilize the protein variants mScarlet, enhanced blue fluorescent protein (EBFP2) and enhanced green fluorescent protein (EGFP) for red, blue and green colors, respectively. The family of fluorescent protein is a well-established biological tool used for fluorescence labelling and pH indication. We demonstrate that the feature of fluorescence is retained after fabrication. We further provide details regarding the fluorescence retention, in particular which fabrication parameters achieve the best outcomes.

Fs-LDW is a promising technique for fine 3D printing of biomaterials such as protein due to nonlinear multiphoton absorption processes facilitating localized microfabrication along a designated laser light path. The use of protein as a precursor material for fs-LDW is attractive because the fabricated structures retain their native functions as demonstrated by several reports. These reports range over various combination of protein and photoactivators, but pure protein can also be utilized as a precursor. The resulting proteinaceous microstructures with native function retained and submicron feature sizes might offer diverse biomedical or biochip applications.

This work highlights the capabilities of fs-LDW from pure protein with a biologically highly regarded protein, broadening the scope of the 3D printing technology as well as providing a new use for the fluorescent protein family.

Transparent ceramics such as magnesium aluminate spinel (MAS) are an outstanding class of materials that combine high optical transparency with remarkable mechanical, chemical and thermal strength. They are particularly interesting for micro-optical applications, since MAS offers a high refractive index in combination with a low optical dispersion, which is inaccessible for other materials including glasses and polymers. However transparent polycrystalline MAS is notoriously difficult to microstructure. Methods such as hot pressing or slip casting only allow simple geometries like plates or domes to be manufactured. More complex geometries require time-consuming and cost-intensive post-processing. We have therefore developed a thermoplastic nanocomposite that can be structured with high accuracy by injection molding. The nanocomposite can subsequently be transformed into a transparent polycrystalline MAS ceramic with a transparency close to the theoretical maximum by thermal debinding, sintering and hot isostatic pressing (HIP). This innovative process makes transparent ceramics for optics and photonics available at low cost and with high production rates.

Polymers are still gaining a lot of interest in the field of optics and sensor technology. Structuring of these components is usually done using high-throughput manufacturing processes such as injection molding, allowing excellent shaping quality and high degree of automation. However, tool production for these tool-based manufacturing methods tends to be time consuming and expensive, limiting the flexibility of these processes. We developed a novel process enabling the fabrication of metallic insets with optical surfaces and structures at the micrometer scale. This involves utilizing high-temperature-stable fused silica glass bodies as molds for metal casting. The process enables the processing of metal alloys such as bronze, brass, and cobalt-chromium at temperatures reaching up to 1400 °C. The metal replications achieve resolutions in the single-digit micrometer range and exhibit a surface roughness in the order of a few nanometers. The manufactured mold tools were successfully tested in a polymer injection molding process.

A miniatured, portable, cost-effective but powerful nano-sieve device is produced and developed for concentrating the targets at low concentrations, leading to the disease diagnostics at point-of-care (POC) settings. To achieve the efficient on-chip concentration of nanoparticles, the multi-sized micro-beads stacking is introduced to this nano-sieve system. Particularly, a flexible PDMS cap is applied to trap the micro-beads in the channel to serve as a three-dimensional filter to physically block and concentrate those nanoparticles, meanwhile allowing the buffer solution to flow through the channel. By coupling with a CRISPR-based assay, our nano-sieve device was expected to be employed for molecular biosensing applications, such as the detection of low light nanoparticles and target RNA, aiming to provide a rapid and efficient multiplexing sample processing at POC environments.

A 3D printed microfluidic device for particle sorting was demonstrated using syringe-based fluid flow. Flow speeds of 192 μm/s were shown. This demonstrated an inexpensive, quick and facile fabrication approach to microfluidic particle sorting.

Genome editing comprises the most promising work in 21st century genetics, with molecular surgery as its practical horizon. For a successful clinical application of molecular surgery, e.g. to treat cancer, safe and efficient editing is crucial. Light-induced molecular surgery is the perfect tool for its excellent control over wavelength, power, and exposure time. Light is also an excellent tool for the detection of (living) cells. These modalities are ideal for opto-fluidics: combining integrated photonics and microfluidics in a chip. In this work, we used the TriPleX^® waveguide platform, comprised of silicon nitride and silicon oxide, to control high power (>1W) visible light. Living cells are inserted into a 100 micrometer wide microfluidic channel after which they are focused into a 25 micrometer wide section in its center using side-, backand lift sheath flows. The cells can be readily recovered at the microfluidic channel’s output with >90% survival rate. Chemically deactivated CRISPR/Cas9 molecules are activated by the laser light for safe molecular surgery. In parallel, it is possible to detect living cells flowing in the microfluidic channel. Measuring light absorption by the analyte makes it possible to detect each individual cell passing by the laser light, and to microscopically verify that >97% of the cells are correctly centered in the microfluidic channel. This device represents a first step to a fully integrated on-chip flow cytometer. Early results demonstrate its efficacy in cell detection and controllable exposure, paving the way to safe molecular surgery.

Monitoring and eradicating bacteria poses a significant challenge in treating periprosthetic joint infections (PJI). Addressing this challenge, the Smart Wireless Implant for Infection Monitoring (SWI2M) project was initiated to enhance treatment efficacy and fulfill unmet needs. The project focuses on developing a sensorized SmartSpacer, replacing the cement spacer in the two-stage revision for infected Total Knee Arthroplasty (TKA). This innovative SmartSpacer will facilitate in vivo observation throughout the infection course by acquiring temperature, imaging, and light-scattering characteristics of synovial fluid. These diverse data enable the determination of propagation of the ongoing infection in grade and level. This document describes the experiments in which Staphylococcus aureus bacterial suspensions were exposed to a broadband light source of the SmartSpacer, resulting in low-resolution scattering spectra and determining the bacterial load concentration based on a statistical algorithm for trend detection.

Dopamine (DA) is an important neurotransmitter in the human body, mainly in the brain. It plays a pivotal role in regulating various physiological functions such as mood regulations and it is crucial for reinforcing behaviors linked to pleasure and survival. Variation of its concentration is a reason for numerous neurological diseases such as Parkinson’s disease which makes its detection vital for early diagnosis and drug screening. Detecting dopamine, however, comes with its own set of challenges, particularly due to the necessity for methods that are highly sensitive and specific. This paper reports an improved method for the detection of exocytotic events from dopaminergic neurons by merging the electrochemical properties of the ion beam induced graphitic electrodes on diamond and the capabilities of a stereolithography (SLA) 3D printer to produce a droplet-based microfluidic biosensor.