Highly Miniaturized, Low-Power CMOS ASIC Chip for Long-Term Continuous Glucose Monitoring.

BACKGROUND: The objective of this work is to develop a highly miniaturized, low-power, biosensing platform for continuous glucose monitoring (CGM). This platform is based on an application-specific integrated circuit (ASIC) chip that interfaces with an amperometric glucose-sensing element. To reduce both size and power requirements, this custom ASIC chip was implemented using 65-nm complementary metal oxide semiconductor (CMOS) technology node. Interfacing this chip to a frequency-counting microprocessor with storage capabilities, a miniaturized transcutaneous CGM system can be constructed for small laboratory animals, with long battery life. METHOD: A 0.45 mm × 1.12 mm custom ASIC chip was first designed and implemented using the Taiwan Semiconductor Manufacturing Company (TSMC) 65-nm CMOS technology node. This ASIC chip was then interfaced with a multi-layer amperometric glucose-sensing element and a frequency-counting microprocessor with storage capabilities. Variation in glucose levels generates a linear increase in frequency response of this ASIC chip. In vivo experiments were conducted in healthy Sprague Dawley rats. RESULTS: This highly miniaturized, 65-nm custom ASIC chip has an overall power consumption of circa 36 µW. In vitro testing shows that this ASIC chip produces a linear (R2 = 99.5) frequency response to varying glucose levels (from 2 to 25 mM), with a sensitivity of 1278 Hz/mM. In vivo testing in unrestrained healthy rats demonstrated long-term CGM (six days/per charge) with rapid glucose response to glycemic variations induced by isoflurane anesthesia and tail vein injection. CONCLUSIONS: The miniature footprint of the biosensor platform, together with its low-power consumption, renders this CMOS ASIC chip a versatile platform for a variety of highly miniaturized devices, intended to improve the quality of life of patients with type 1 and type 2 diabetes.

Amino acid-modified chitosan nanoparticles for Cu2+ chelation to suppress CuO nanoparticle cytotoxicity.

The extensive development and application of engineered nanoparticles (NPs) in various fields worldwide have been subjected to increasing concern due to their potential hazards to human health and the environment. Therefore, a simple, economical, and effective method for suppressing the toxicity of metal-based nanomaterials is needed. In this study, glutaraldehyde-crosslinked chitosan nanoparticles (CS NPs) were prepared and further modified with lysine (Ly-CS), glutamic acid (Glu-CS), or sodium borohydride reduction (R-CS), and used to suppress cytotoxicity induced by copper oxide NPs (CuO NPs) through chelation with intracellularly released copper ions. All three kinds of CS NPs had similar sizes of ∼100 nm in a dry state and ∼200 nm in cell culture medium, as determined by scanning electron microscopy, transmission electron microscopy, and dynamic light scattering. The chelating efficiency of different CS NPs followed the order Ly-CS > Glu-CS > R-CS. The CS NPs showed minimal or no toxicity to three different cell lines (HepG2, A549, and RAW264.7 cells) at 100 µg mL-1 with similar cell internalization and exocytosis processes. Comparatively, RAW264.7 cells exhibited higher endocytosis and exocytosis rates, as revealed by flow cytometry and confocal laser scanning microscopy. CS NPs were found as agglomerates inside A549 cells and RAW264.7 cells, with the amount of agglomerates inside RAW264.7 cells decreasing significantly with prolonged incubation. All three CS NPs, especially Ly-CS and Glu-CS NPs, efficiently suppressed the cytotoxicity induced by CuO NPs, and reduced the intracellular level of reactive oxygen species.

Exploring Dynamic Equilibrium of Diels-Alder Reaction for Solid State Plasticity in Remoldable Shape Memory Polymer Network.

The reversible and click nature of Diels-Alder (DA) reactions has made them ideal candidates to design materials with nonconventional properties. Most commonly, the reversibility of DA is utilized for designing thermosets that can be liquefied for reprocessing and self-healing, yet the dynamic equilibrium nature has been largely neglected. In this work, shape memory polymers (SMP) containing DA moieties in the networks were synthesized. In addition to its remoldability at the liquid state at sufficiently high temperatures (above 110 °C), we show uniquely and surprisingly that such a network can undergo plastic deformation in its solid state at intermediate temperatures (60-100 °C) by taking advantage of its dynamic equilibrium for network topological rearrangement. The liquid state remoldability and solid state plasticity represent two distinct yet complementary mechanisms to manipulate the permanent shape of an SMP, leading to unprecedented versatility that can benefit a variety of applications in the future.