Polydopamine surface functionalization of 3D printed resin material for enhanced polystyrene adhesion towards insulation layers for 3D microelectrode arrays (3D MEAs).

3D printing involves the use of photopolymerizable resins, which are toxic and typically have incompatible properties with materials such as polystyrene (PS), which present limitations for biomedical applications. We present a method to dramatically improve the poor adhesion between the PS insulative layer on 3D printed Microelectrode Array (MEA) substrates by functionalizing the resin surface with polydopamine (PDA), a mussel-inspired surface chemistry derivative. A commercial 3D printing prepolymer resin, FormLabs Clear (FLC), was printed using a digital light processing (DLP) printer and then surface functionalized with PDA by alkali-induced aqueous immersion deposition and self-polymerization. It was observed that the adhesion of the PS to FLC was improved due to the precision emanating from the DLP method and further improved after the functionalization of DLP printed substrates with PDA at 1, 12, and 24 h time intervals. The adhesion of PS was evaluated through scotch tape peel testing and instron measurements of planar substrates and incubation testing with qualitative analysis of printed culture wells. The composition and topology of the samples were studied to understand how the properties of the surface change after PDA functionalization and how this contributes to the overall improvement in PS adhesion. Furthermore, the surface energies at each PDA deposition time were calculated from contact angle studies as it related to adhesion. Finally, biocompatibility assays of the newly modified surfaces were performed using mouse cardiac cells (HL-1) to demonstrate the biocompatibility of the PDA functionalization process. PDA surface functionalization of 3D DLP printed FLC resin resulted in a dramatic improvement of thin film PS adhesion and proved to be a biocompatible solution for improving additive manufacturing processes to realize biosensors such as in vitro MEAs.

Fabrication and Characterization of 3D Printed, 3D Microelectrode Arrays for Interfacing with a Peripheral Nerve-on-a-Chip.

We present a nontraditional fabrication technique for the realization of three-dimensional (3D) microelectrode arrays (MEAs) capable of interfacing with 3D cellular networks in vitro. The technology uses cost-effective makerspace microfabrication techniques to fabricate the 3D MEAs with 3D printed base structures with the metallization of the microtowers and conductive traces being performed by stencil mask evaporation techniques. A biocompatible lamination layer insulates the traces for realization of 3D microtower MEAs (250 µm base diameter, 400 µm height). The process has additionally been extended to realize smaller electrodes (30 µm × 30 µm) at a height of 400 µm atop the 3D microtower using laser micromachining of an additional silicon dioxide (SiO2) insulation layer. A 3D microengineered, nerve-on-a-chip in vitro model for recording and stimulating electrical activity of dorsal root ganglion (DRG) cells has further been integrated with the 3D MEA. We have characterized the 3D electrodes for electrical, chemical, electrochemical, biological, and chip hydration stability performance metrics. A decrease in impedance from 1.8 kΩ to 670 Ω for the microtower electrodes and 55 to 39 kΩ for the 30 µm × 30 µm microelectrodes can be observed for an electrophysiologically relevant frequency of 1 kHz upon platinum electroless plating. Biocompatibility assays on the components of the system resulted in a large range (∼3%-70% live cells), depending on the components. Fourier-transform infrared (FTIR) spectra of the resin material start to reveal possible compositional clues for the resin, and the hydration stability is demonstrated in in-vitro-like conditions for 30 days. The fabricated 3D MEAs are rapidly produced with minimal usage of a cleanroom and are fully functional for electrical interrogation of the 3D organ-on-a-chip models for high-throughput of pharmaceutical screening and toxicity testing of compounds in vitro.

Controlled drug release from polyelectrolyte-drug conjugate nanoparticles.

Encapsulating drugs in functional nanoparticles provides controlled and targeted release of drugs. In this study, a general approach for encapsulating hydrophobic drugs in polyelectrolyte nanoparticles was developed for a controlled drug release. Gemcitabine (GEM), an anticancer drug for pancreatic ductal adenocarcinoma (PDAC), was used as a model drug to produce poly(acrylic acid) (PAA)-GEM conjugate nanoparticles to achieve a controlled release of GEM in cells. The PAA-GEM conjugate nanoparticles were fabricated by coupling GEM onto PAA through the formation of amide bonds. The hydrophobic interactions of GEM molecules induced the formation of the nanoparticles with the GEM core and PAA shell. Fabrication conditions such as the PAA/GEM ratio and pH were optimized to achieve high structure stability and drug loading efficiency. The size and surface charge of the nanoparticles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurement. The optimized PAA-GEM nanoparticles had a size around 12 nm, 30 nm and 60 nm in dry state, water, and phosphate buffered saline (PBS), respectively. The encapsulation efficiency was 29.29 ± 1.7%, and the loading capacity was 9.44 ± 0.46%. Less than 7% GEM was released from the PAA-GEM nanoparticles after 96 hour incubation in phosphate buffered saline. The cytotoxic efficacy of the PAA-GEM nanoparticles in cancer cells was investigated through viability studies of PANC-1, a human pancreatic cancer cell line. It was found that the PAA-GEM nanoparticles had more than a 48 hour delay of releasing GEM and had the same cytotoxic efficacy in PANC-1 cells as free GEM. The uptake of the PAA-GEM nanoparticles by PANC-1 cells was investigated using PAA-GEM labeled by rhodamine G6. Fluorescence and bright field overlay images indicated that the PAA-GEM nanoparticles were taken up by PANC-1 cells within 2 hours. It is believed that the PAA-GEM nanoparticles were decomposed in PANC-1 cells and GEM was released from the nanoparticles.

A Microfluidic MEMS-Microbalance Platform With Minimized Acoustic Radiation in Liquid.

In this article, the microfluidic channels that deliver liquid to a microscale thin-film piezoelectric-on-silicon (TPoS) gravimetric resonant sensor are incorporated into the backside of the silicon-on-insulator (SOI) wafer on which the resonator is fabricated. Specifically, a microwell is embedded at the bottom of the disk -shaped TPoS resonator, while a very thin layer of parylene covering the backside of the resonator and the microwell forms an isolation layer between the liquid and the top device-layer features. In this way, the liquid is in contact with the backside of the resonator, while the device-defining trenches and the electrical connections to the resonator stay clear, thus mitigating the acoustic energy loss and undesirable feedthroughs. The impact of the parylene layer thickness on a few symmetric ( S ) and antisymmetric ( A ) Lamb wave modes of the resonator is experimentally studied, and the performance of such modes in the liquid is characterized by filling the microwells through a PDMS-based microfluidic channel. The parylene layer, while marginally affecting the resonator in the air, is found to substantially enhance its performance in the liquid media. Strong resonance peaks with high quality factors ( Q ) are observed for the S modes, among which Q values above 400 are recorded for a specific mode named S (4, 2) (among the highest ever reported). This article can potentially facilitate the realization of highly stable and sensitive resonant mass sensors (i.e., microbalance) for real-time applications. Additionally, the effect of the acoustic energy radiation in the form of evanescent shear and longitudinal waves in liquid on the Q and resonance frequency of the disk resonators is experimentally validated.

Nanomaterials in Advanced, High-Performance Aerogel Composites: A Review.

Aerogels are one of the most interesting materials of the 21st century owing to their high porosity, low density, and large available surface area. Historically, aerogels have been used for highly efficient insulation and niche applications, such as interstellar particle capture. Recently, aerogels have made their way into the composite universe. By coupling nanomaterial with a variety of matrix materials, lightweight, high-performance composite aerogels have been developed for applications ranging from lithium-ion batteries to tissue engineering materials. In this paper, the current status of aerogel composites based on nanomaterials is reviewed and their application in environmental remediation, energy storage, controlled drug delivery, tissue engineering, and biosensing are discussed.