Shape complementarity processes for ultrashort-burst sensitive M13-PEG-WS2-powered MCF-7 cancer cell sensors.

Biomarkers have the potential to be utilized in disease diagnosis, prediction and monitoring. The cancer cell type is a leading candidate for next-generation biomarkers. Although traditional digital biomolecular sensor (DBS) technology has shown to be effective in assessing cell-based interactions, low cell-population detection of cancer cell types is extremely challenging. Here, we controlled the electrical signature of a two-dimensional (2D) nanomaterial, tungsten disulfide (WS2), by utilizing a combination of the Phage-integrated Polymer and the Nanosheet (PPN), viz., the integration of the M13-conjugated polyethylene glycol (PEG) and the WS2, through shape-complementarity phenomena, and developed a sensor system, i.e., the Phage-based DBS (P-DBS), for the specific, rapid, sensitive detection of clinically-relevant MCF-7 cells. The P-DBS attains a detection limit of 12 cells per µL, as well as a contrast of 1.25 between the MCF-10A sample signal and the MCF-7 sample signal. A reading length of 200 µs was further achieved, along with a relative cell viability of ∼100% for both MCF-7 and MCF-10A cells and with the PNN. Atomistic simulations reveal the structural origin of the shape complementarity-facilitated decrease in the output impedance of the P-DBS. The combination of previously unreported exotic sensing materials and digital sensor design represents an approach to unlocking the ultra-sensitive detection of cancer cell types and provides a promising avenue for early cancer diagnosis, staging and monitoring.

Ultrafast Near-Ideal Phase-Change Memristive Physical Unclonable Functions Driven by Amorphous State Variations.

There is an ever-increasing demand for next-generation devices that do not require passwords and are impervious to cloning. For traditional hardware security solutions in edge computing devices, inherent limitations are addressed by physical unclonable functions (PUF). However, realizing efficient roots of trust for resource constrained hardware remains extremely challenging, despite excellent demonstrations with conventional silicon circuits and archetypal oxide memristor-based crossbars. An attractive, down-scalable approach to design efficient cryptographic hardware is to harness memristive materials with a large-degree-of-randomness in materials state variations, but this strategy is still not well understood. Here, the utilization of high-degree-of-randomness amorphous (A) state variations associated with different operating conditions via thermal fluctuation effects is demonstrated, as well as an integrated framework for in memory computing and next generation security primitives, viz., APUF, for achieving secure key generation and device authentication. Near ideal uniformity and uniqueness without additional initial writing overheads in weak memristive A-PUF is achieved. In-memory computing empowers a strong exclusive OR (XOR-) and-repeat A PUF construction to avoid machine learning attacks, while rapid crystallization processes enable large-sized-key reconfigurability. These findings pave the way for achieving a broadly applicable security primitive for enhancing antipiracy of integrated systems and product authentication in supply chains.

WS2/Polyethylene Glycol Nanostructures for Ultra-Efficient MCF-7 Cancer Cell Ablation and Electrothermal Therapy.

Developing novel nanostructures and advanced nanotechnologies for cancer treatment has attracted ever-increasing interest. Electrothermal therapy offers many advantages such as high efficiency and minimal invasiveness, but finding a balance between increasing stability of the nanostructure state and, at the same time, enhancing the nanostructure biodegradability presents a key challenge. Here, we modulate the biodegradation process of two-dimensional-material-based nanostructures by using polyethylene glycol (PEG) via nanostructure disrupt-and-release effects. We then demonstrate the development of a previously unreported alternating current (AC) pulse WS2/PEG nanostructure system for enhancing therapeutic performance. A decrease in cell viability of ∼42% for MCF-7 cells with WS2/PEG was achieved, which is above an average of ∼25% for current electrothermal-based therapeutic methods using similar energy densities, as well as degradation time of the WS2 of ∼1 week, below an average of ∼3.5 weeks for state-of-the-art nanostructure-based systems in physiological media. Moreover, the incubation time of MCF-7 cells with WS2/PEG reached ∼24 h, which is above the average of ∼4.5 h for current electrothermal-based therapeutic methods and with the use of the amount of time harnessed to incubate the cells with nanostructures before applying a stimulus as a measure of incubation time. Material characterizations further disclose the degradation of WS2 and the grafting of PEG on WS2 surfaces. These WS2-based systems offer strong therapeutic performance and, simultaneously, maintain excellent biodegradability/biocompatibility, thus providing a promising route for the ablation of cancer.

An Efficient, Short Stimulus PANC-1 Cancer Cell Ablation and Electrothermal Therapy Driven by Hydrophobic Interactions.

Promising results in clinical studies have been demonstrated by the utilization of electrothermal agents (ETAs) in cancer therapy. However, a difficulty arises from the balance between facilitating the degradation of ETAs, and at the same time, increasing the electrothermal performance/stability required for highly efficient treatment. In this study, we controlled the thermal signature of the MoS2 by harnessing MoS2 nanostructures with M13 phage (MNM) via the structural assembling (hydrophobic interaction) phenomena and developed a combined PANC-1 cancer cell-MNM alternating current (AC)-stimulus framework for cancer cell ablation and electrothermal therapy. A percentage decrease in the cell viability of ~23% was achieved, as well as a degradation time of 2 weeks; a stimulus length of 100 µs was also achieved. Molecular dynamics (MD) simulations revealed the assembling kinetics in integrated M13 phage-cancer cell protein systems and the structural origin of the hydrophobic interaction-enabled increase in thermal conduction. This study not only introduced an 'ideal' agent that avoided the limitations of ETAs but also provided a proof-of-concept application of MoS2-based materials in efficacious cancer therapy.