Hsien-Yeh Chen

The insulation performance of reactive parylene films in implantable electronic devices

Parylene-C (poly-chloro-p-xylylene) is an appropriate material for use in an implantable, microfabricated device. It is hydrophobic, conformally deposited, has a low dielectric constant, and superb biocompatibility. Yet for many bioelectrical applications, its poor wet adhesion may be an impassable shortcoming. This research contrasts parylene-C and poly(p-xylylene) functionalized with reactive group X (PPX-X) layers using long-term electrical soak and adhesion tests. The reactive parylene was made of complementary derivatives having aldehyde and aminomethyl side groups (PPX-CHO and PPX-CH2NH2 respectively). These functional groups have previously been shown to covalently react together after heating. Electrical testing was conducted in saline at 37 degrees C on interdigitated electrodes with either parylene-C or reactive parylene as the metal layer interface. Results showed that reactive parylene devices maintained the highest impedance. Heat-treated PPX-X device impedance was 800% greater at 10kHz and 70% greater at 1Hz relative to heated parylene-C controls after 60 days. Heat treatment proved to be critical for maintaining high impedance of both parylene-C and the reactive parylene. Adhesion measurements showed improved wet metal adhesion for PPX-X, which corresponds well with its excellent high frequency performance.

Solventless adhesive bonding using reactive polymer coatings.

A novel solventless adhesive bonding (SAB) process is reported, which is applicable to a wide range of materials including, but not limited to, poly(dimethylsiloxane) (PDMS). The bonding is achieved through reactions between two complementary polymer coatings, poly(4-aminomethyl-p-xylylene-co-p-xylylene) and poly(4-formyl-p-xylylene-co-p-xylylene), which are prepared by chemical vapor deposition (CVD) polymerization of the corresponding [2.2]paracyclophanes and can be deposited on complementary microfluidic units to be bonded. These CVD-based polymer films form well-adherent coatings on a range of different substrate materials including polymers, glass, silicon, metals, or paper and can be stored for extended periods prior to bonding without losing their bonding capability. Tensile stress data are measured on PDMS with various substrates and compared favorably to current methods such as oxygen plasma and UV/ozone. Sum frequency generation (SFG) has been used to probe the presence of amine and aldehyde groups on the surface after CVD polymerization and their conversion during bonding. In addition to bonding, unreacted functional groups present on the luminal surface of microfluidic channels provide free chemical groups for further surface modification. Fluorescently labeled molecules including rhodamine-conjugated streptavidin and atto-655 NHS ester were used to verify the presence of active functional groups on the luminal surfaces after bonding.

Designable biointerfaces using vapor-based reactive polymers

Functionalized poly(p-xylylenes) constitute a versatile class of reactive polymers that can be prepared in a solventless process via chemical vapor deposition (CVD) polymerization. The resulting ultrathin coatings are typically pinhole-free and can be conformally deposited onto a wide range of substrates and materials. More importantly, appropriately selected functional groups can serve as anchoring sites for tailoring biointerface properties via the immobilization of biomolecules. In this article, controlled surface chemistries are outlined that use functionalized poly(p-xylylenes) as reactive coatings, including alkyne-functionalized coatings for Huisgen 1,3-dipolar cycloaddition reactions or aldehyde-functionalized coatings. The reactive coatings technology provides flexible access to a range of different surface chemistries, enabling a broad range of potential applications in microfluidics, medical device coatings, and biotechnology. In this feature article, we will highlight recent progress in vapor-based reactive coatings and will discuss potential benefits and current limitations.

Fully monolithic CMOS nickel micromechanical resonator oscillator

A fully monolithic oscillator achieved via MEMS-last integration of low temperature nickel micromechanical resonator arrays over finished foundry CMOS circuitry has been demonstrated with a measured phase noise of -95 dBc/Hz at a 10-kHz offset from its 10.92-MHz carrier (i.e., output) frequency. The use of a side-supported flexural-mode disk resonator-array to boost the power handling of the resonant tank is instrumental to allowing adequate oscillator performance despite the use of low-temperature nickel structural material. Because the fabrication steps for the resonator-array never exceed 50degC, the process is amenable to not only MEMS-last monolithic integration with the 0.35 mum CMOS of this work, but also next generation CMOS with gate lengths 65 nm and smaller that use advanced low-k dielectric material to lower interconnect capacitance.

Substrate-independent dip-pen nanolithography based on reactive coatings

We report that nanostructuring via dip-pen nanolithography can be used for modification of a broad range of different substrates (polystyrene, Teflon, stainless steel, glass, silicon, rubber, etc.) without the need for reconfiguring the underlying printing technology. This is made possible through the use of vapor-based coatings that can be deposited on these substrates with excellent conformity, while providing functional groups for subsequent spatially directed click chemistry via dip-pen nanolithography. Pattern quality has been compared on six different substrates demonstrating that this approach indeed results in a surface modification protocol with potential use for a wide range of biotechnological applications.

Reactive Polymer Coatings: A General Route to Thiol-ene and Thiol-yne Click Reactions

Reactive polymer coatings were synthesized via chemical vapor deposition (CVD) polymerization process. These coatings decouple surface design from bulk properties of underlying materials and provide a facile and general route to support thiol-ene and thiol-yne reactions on a variety of substrate materials. Through the reported technique, surface functions can be activated through a simple design of thiol-terminated molecules such as polyethylene glycols (PEGs) or peptides (GRGDYC), and the according biological functions were demonstrated in controlled and low-fouling protein adsorptions as well as accurately manipulated cell attachments.

Colloids with high-definition surface structures

Compared with the well equipped arsenal of surface modification methods for flat surfaces, techniques that are applicable to curved, colloidal surfaces are still in their infancy. This technological gap exists because spin-coating techniques used in traditional photolithographic processes are not applicable to the curved surfaces of spherical objects. By replacing spin-coated photoresist with a vapor-deposited, photodefinable polymer coating, we have now fabricated microstructured colloids with a wide range of surface patterns, including asymmetric and chiral surface structures, that so far were typically reserved for flat substrates. This high-throughput method can yield surface-structured colloidal particles at a rate of ≈107 to 108 particles per operator per day. Equipped with spatially defined binding pockets, microstructured colloids can engage in programmable interactions, which can lead to directed self-assembly. The ability to create a wide range of colloids with both simple and complex surface patterns may contribute to the genesis of previously unknown colloidal structures and may have important technological implications in a range of different applications, including photonic and phononic materials or chemical sensors.

The Use of Reactive Polymer Coatings to Facilitate Gene Delivery from Poly (ε-caprolactone) Scaffolds

To functionalize biomaterials for bioconjugation, a chemical vapor deposition (CVD) polymerization technique was utilized to modify material surfaces. Poly [(4-amino-p-xylylene)-co-(p-xylylene)] (PPX-NH(2)) was deposited on inert polycaprolactone (PCL) surfaces to provide a reactive amine layer on the substrate surfaces. The biocompatibility of PPX-NH(2) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase (LDH) assays. The results demonstrated that cells continuously proliferated on CVD treated PCL surfaces with high survival rates. Biotin was conjugated on modified PCL surfaces to immobilize avidin for binding of biotinylated adenovirus. Scanning electron microscopy (SEM) examination illustrated that adenoviruses were evenly bound on both 2-D films and 3-D scaffolds, suggesting CVD was capable of modifying various substrates with different geometries. Using a wax masking technique, the biotin conjugation was controlled to immobilize avidin on specific sites. Due to the virus binding specificity on CVD-modified surfaces, cell transduction was restricted to the pattern of immobilized virus on biomaterials, by which transduced and non-transduced cells were controlled in different regions with a distinct interface. Because CVD was functional in different hierarchies, this surface modification should be able to custom-tailor bioconjugation for different applications.

Vapor-based tri-functional coatings†

The tri-functional coating synthesized via CVD copolymerization is comprised of distinguished anchoring sites of acetylene, maleimide, and ketone that can synergically undergo specific conjugation reactions to render surfaces with distinct biological functions, simultaneously. In addition, these tri-functional coatings can be fabricated in a micro-structured fashion on non-conventional surfaces.

Compatibility balanced antibacterial modification based on vapor-deposited parylene coatings for biomaterials

Advanced antibacterial surfaces are designed based on covalently attached antibacterial agents, avoiding potential side effects associated with overdosed or eluted agents. The technique is widely applicable regardless of the underlying substrate material. In addition, antibacterial surfaces are effective against the early stages of bacterial adhesion and can significantly reduce the formation of biofilm, without compromising biocompatibility. Here, this concept was realized by employing a benzoyl-functionalized parylene coating. The antibacterial agent chlorhexidine was used as a proof of concept. Chlorhexidine was immobilized by reaction with photoactivated benzoyl-functionalized surfaces, including titanium alloy, stainless steel, polyether ether ketone, polymethyl methacrylate, and polystyrene. A low concentration of chlorhexidine (1.4 ± 0.08 nmol cm-2) covalently bound to surfaces rendered them sufficiently resistant to an Enterobacter cloacae inoculum and its adherent biofilm. Compared to unmodified surfaces, up to a 30-fold reduction in bacterial attachment was achieved with this coating technology. The immobilization of chlorhexidine was verified with infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS), and a leaching test was performed to confirm that the chlorhexidine molecules were not dislodged. Cell compatibility was examined by culturing fibroblasts and osteoblasts on the modified surfaces, revealing greater than 93% cell viability. This coating technology may be broadly applicable for a wide range of other antibacterial agents and allow the design of new biomaterials.