Jeffrey M. Halpern

A biodegradable thermoset polymer made by esterification of citric acid and glycerol.

A new biomaterial, a degradable thermoset polymer, was made from simple, economical, biocompatable monomers without the need for a catalyst. Glycerol and citric acid, nontoxic and renewable reagents, were crosslinked by a melt polymerization reaction at temperatures from 90 to 150°C. Consistent with a condensation reaction, water was determined to be the primary byproduct. The amount of crosslinking was controlled by the reaction conditions, including temperature, reaction time, and ratio between glycerol and citric acid. Also, the amount of crosslinking was inversely proportional to the rate of degradation. As a proof-of-principle for drug delivery applications, gentamicin, an antibiotic, was incorporated into the polymer with preliminary evaluations of antimicrobial activity. The polymers incorporating gentamicin had significantly better bacteria clearing of Staphylococcus aureus compared to non-gentamicin gels for up to 9 days.

Thermomechanical properties, antibiotic release, and bioactivity of a sterilized cyclodextrin drug delivery system

Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin-hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p<0.0001) compared to non-sterilized polymers . In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p<0.05) and a prolonged therapeutic effect (p<0.05) but less drug loading (p<0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials.

Wireless Amperometric Neurochemical Monitoring Using an Integrated Telemetry Circuit

An integrated circuit for wireless real-time monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting high-resolution amperometric measurements in four settings of the input current. The chip architecture includes a first-order DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed (FSK) voltage-controlled oscillator (VCO) operating near 433 MHz. It is fabricated using the AMI 0.5 mum double-poly triple-metal n -well CMOS process, and requires only one off-chip component for operation. Measured dc current resolutions of ~ 250 fA, ~ 1.5 pA, ~ 4.5 pA, and ~ 17 pA were achieved for input currents in the range of plusmn5, plusmn37, plusmn150, and plusmn600 nA, respectively. The chip has been interfaced with a diamond-coated, quartz-insulated, microneedle, tungsten electrode, and successfully recorded dopamine concentration levels as low as 0.5 muM wirelessly over a transmission distance of ~ 0.5 m in flow injection analysis experiments.

Differentiation between genetic mutations of breast cancer by breath volatolomics

Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.

Diamond Microelectrodes and CMOS Microelectronics for Wireless Transmission of Fast-Scan Cyclic Voltammetry

This paper reports on technology development at the sensor and circuit levels for wireless transmission of fast- scan cyclic voltammetry (FSCV) in neurochemical detection. Heavily conductive, boron-doped diamond is selectively deposited onto the polished tip of a tungsten microelectrode to fabricate versatile, implantable, micro-needle microprobes capable of neurochemical sensing in the brain. In addition, an integrated circuit is fabricated in a 0.5-mum CMOS technology for processing and wireless transmission of the electrochemical signals corresponding to extracellular concentration changes of various neurotransmitters. The chip consists of a current-based, second-order, front-end SigmaDelta ADC and an on-chip, RF-FSK transmitter at the back-end. The ADC core and the transmitter consume 22 muA and 400 muA, respectively, from a 2.6-V power supply. Major electroactive neurotransmitters such as serotonin and dopamine in micromolar concentration have been wirelessly recorded at 433 MHz using 300-V/s FSCV in flow injection analysis experiments.

Controlling the Sensing Properties of Silicon Nanowires via the Bonds Nearest to the Silicon Nanowire Surface

Controlling the sensing properties of a silicon nanowire field effect transistor is dependent on the surface chemistry of the silicon nanowire. A standard silicon nanowire has a passive oxide layer (native oxide), which has trap states that cause sensing inaccuracies and desensitize the surface to nonpolar molecules. In this paper, we successfully modified the silicon nanowire surface with different nonoxide C3 alkyl groups, specifically, propyl (Si-CH2-CH2-CH3), propenyl (Si-CH═CH-CH3), and propynyl (Si-C≡C-CH3) modifications. The effect of the near surface bond on the sensor sensitivity and stability was explored by comparing three C3 surface modifications. A reduction of trap-states led to greater sensor stability and accuracy. The propenyl-modified sensor was consistently the most stable and sensitive sensor, among the applied sensors. The propenyl- and propynyl-modified sensors consistently performed with the best accuracy in identifying specific analytes with similar polarity or similar molecular weights. A combination of features from different sensing surfaces led to the best rubric for specific analytes identification. These results indicate that nonoxide sensor surfaces are useful in identifying specific analytes and that a combination of sensors with different surfaces in a cross-reactive array can lead to specific analytes detection.

Kinetic and Adsorption Studies of Biogenic Amine Neurotransmitters at Polycrystalline Diamond Microelectrodes

High sensitivity, 1-10 nM detection, of biogenic amine neurotransmitters was achieved using fast-scan cyclic voltammetry at hydrogen-terminated diamond microelectrodes. This reduced to 1-10 μM after 5-10 runs. To attempt to understand the sensitivity decrease, electron transfer kinetics, baseline current, and rate-limiting step for high (μM) and low (nM) concentrations were compared. Dopamine oxidation kinetics slowed after repeated scans, ΔEp increased from 0.142 to 0.805 V. Baseline current decreased by 50%. The rate-limiting step, measured only at the conditioned surface, was diffusion limiting. The high quality of our electrodes was verified by the voltage window in 0.5 M H2SO4 and by Raman spectroscopy. Dopamine and serotonin oxidation kinetics were characterized at more sensitive, sulfophenyl-terminated diamond microelectrodes; the responses were diffusion limited. These data were qualitatively consistent with surface chemistry changes after scanning, but do not adequately explain the sensitivity decrease. Additional testing of hydrogen- terminated surfaces is needed to provide insight.