Objective We focus on improving the long-term stability and functionality of neural interfaces for chronic implantation by using bilayer encapsulation. Approach We evaluated the long-term reliability of Utah electrode array (UEA) based neural interfaces encapsulated by 52 nm of atomic layer deposited (ALD) Al2O3 and 6 μm of Parylene C bilayer, and compared these to devices with the baseline Parylene-only encapsulation. Three variants of arrays including wired, wireless, and active UEAs were used to evaluate this bilayer encapsulation scheme, and were immersed in phosphate buffered saline (PBS) at 57 °C for accelerated lifetime testing. Main results The median tip impedance of the bilayer encapsulated wired UEAs increased from 60 kΩ to 160 kΩ during the 960 days of equivalent soak testing at 37 °C, the opposite trend as typically observed for Parylene encapsulated devices. The loss of the iridium oxide tip metallization and etching of the silicon tip in PBS solution contributed to the increase of impedance. The lifetime of fully integrated wireless UEAs was also tested using accelerated lifetime measurement techniques. The bilayer coated devices had stable power-up frequencies at ~910 MHz and constant RF signal strength of -50 dBm during up to 1044 days (still under testing) of equivalent soaking time at 37 °C. This is a significant improvement over the lifetime of ~ 100 days achieved with Parylene-only encapsulation at 37 °C. The preliminary samples of bilayer coated active UEAs with a flip-chip bonded ASIC chip had a steady current draw of ~ 3 mA during 228 days of soak testing at 37 °C. An increase in current draw has been consistently correlated to device failures, so is a sensitive metric for their lifetime. Significance The trends of increasing electrode impedance of wired devices and performance stability of wireless and active devices support the significantly greater encapsulation performance of this bilayer encapsulation compared with Parylene-only encapsulation. The bilayer encapsulation should significantly improve the in vivo lifetime of neural interfaces for chronic implantation.

We describe the basis for an affinity biosensor platform in which enhanced fluorescence transduction occurs through the optical excitation of molecules located within metallic nanocavities. These nanocavities are about 200 nm in diameter, are arranged in periodic or random two-dimensional arrays, and are fabricated in 70 nm thick gold films by e-beam lithography using negative e-beam resist. The experimental results show that both periodic and randomly placed metallic nanocavities can be used to enhance the fluorescence output of molecules within the cavities by about a factor of ten. In addition, the platform provides isolation from fluorescence produced by unbound species, making it suitable for real-time detection. Finally, we demonstrate the use of the platform in the real-time detection of 20-base oligonucleotides in solution.

Surface plasmon resonance (SPR) is a popular technique for label-free detection of biomolecular interactions at a surface. SPR yields quantitative kinetic association and dissociation constants of surface interactions such as the binding of two molecular species, one present in the liquid phase and the other immobilized at the surface. Current state-of-the-art SPR systems extract kinetic constants from measurements of the step response of the interaction versus time. The step response measurement is subject to the influence of noise and drift disturbances that limit its minimum-detectable mass changes. This paper presents a new SPR technique that measures the biomolecular interaction not in time but over a very narrow frequency range under periodic excitation. The measured response is, thus, locked to a very specific narrow band signal. This narrow band spectral sensing scheme has a very high degree of rejection to uncorrelated spurious signals. The signal-locked SPR technique was implemented using a chemical modulator chip connected to a set of functionalized Au sensing sites downstream. Binding experiments for a model system of carbonic anhydrase-II (CA-II) analyte and immobilized 4-(2-aminoethyl)benzenesulfonamide (ABS) ligand display a 100-fold (20 dB) improvement in the measured signal-to-noise ratio (SNR) when using the new technique compared to the SNR achieved using the conventional step response method.

Label-free techniques such as surface plasmon resonance (SPR) have used a step-response excitation method to characterize the binding of two biochemical entities. A major drawback of the step response technique is its high susceptibility to thermal drifts and noise which directly determine the minimum detectable binding mass. In this paper we present a new frequency-domain method based on the use of multisine chemical excitation that is much less sensitive to these disturbances. The multisine method was implemented in a PDMS microfluidic chip using a dual channel, dual multiplug chemical signal generator connected to functionalized and reference SPR binding spots. Kinetic constants for the reaction are extracted from the characteristics of the sense spot response versus frequency. The feasibility of the technique was tested using a model system of Carbonic Anhydrase-II analyte and amino-benzenesulfonamide ligand. The experimental signal to noise ratio (SNR) for the multisine measurement is about 32 dB; 7 dB higher than that observed with the single step-response method, while the overall measurement time is twice as long as the step method.

DNA intercalators are planar molecules that insert between the base pairs of duplex DNA. Intercalation into DNA necessarily results in changes in DNA conformation, separating base pairs along the helical axis; thus, intercalators are of great importance as probes of nucleic acid structure and as interferents of DNA replication, transcription, and/or topoisomerase activities. Relationships between structures of intercalators and the changes they cause in DNA conformation are subtle and remain unresolved. An intercalating drug molecule has been synthesized that incorporates markers easily distinguished by atomic force microscopy (AFM). This specially designed psoralen derivative has been intercalated into DNA. To facilitate recognition of the point of intercalation, the psoralen derivative contained a biotin moiety that was exposed and bound readily to streptavidin-coated colloidal gold beads. Atomic force micrographs were obtained following electrostatic immobilization of the DNA/psoralen complexes onto mica surfaces. This article presents AFM images of intercalating drug–DNA complexes which may provide further data for the study of structure/intercalator relationships.