Internalization of subcellular-scale microfabricated chips by healthy and cancer cells

<div><p>Continuous monitoring of physiological parameters inside a living cell will lead to major advances in our understanding of biology and complex diseases, such as cancer. It also enables the development of new medical diagnostics and therapeutics. Progress in nanofabrication and wireless communication has opened up the potential of making a wireless chip small enough that it can be wholly inserted into a living cell. To investigate how such chips could be internalized into various types of living single cells and how this process might affect cells’ physiology, we designed and fabricated a series of multilayered micron-scale tag structures with different sizes as potential RFID (<u>R</u>adio <u>F</u>requency <u>ID</u>entification) cell trackers. While the present structures are test structures that do not resonate, the tags that do resonate have similar structure from device fabrication, material properties, and device size point of view. The structures are in four different sizes, the largest with the lateral dimension of 9 μm × 21 μm. The thickness for these structures is kept constant at 1.5 μm. We demonstrate successful delivery of our fabricated chips into various types of living cells, such as melanoma skin cancer, breast cancer, colon cancer and healthy/normal fibroblast skin cells. To our surprise, we observed a remarkable internalization rate difference between each cell type; the uptake rate was faster for more aggressive cancer cells than the normal/healthy cells. Cell viability before and after tag cellular internalization and persistence of the internalized tags have also been recorded over the course of five days of incubation. These results establish the foundations of the possibility of long term, wireless, intracellular physiological signal monitoring.</p></div

The percentage number of internalized tags into various types of living cells for 12 hours of cell tag incubation.

<p>The percentage number of internalized tags into various types of living cells for 12 hours of cell tag incubation.</p

Internalization of fabricated tag structures into the melanoma skin cancer cells.

<p>The time sequence images of two internalization events for two tag sizes: (a) 9 μm × 15 μm and (b) 9 μm × 21 μm. (c) The Z-sectional images of the fluorescent labeled cells and tag with the depth of focus varies by 1 μm, the tag size is 9 μm × 18 μm.</p

Melanoma skin cancer cells incubated with fabricated tag structures.

<p>(a) The bright field images of 4 different sizes of tags are delivered into the melanoma skin cancer cells. (b) The confluent culture of the melanoma cancer cells after 30 hours, and (c) 5 days of incubation with the tags.</p

Statistical Study on the Schottky Barrier Reduction of Tunneling Contacts to CVD Synthesized MoS₂

Creating high-quality, low-resistance contacts is essential for the development of electronic applications using two-dimensional (2D) layered materials. Many previously reported methods for lowering the contact resistance rely on volatile chemistry that either oxidize or degrade in ambient air. Nearly all reported efforts have been conducted on only a few devices with mechanically exfoliated flakes which is not amenable to large scale manufacturing. In this work, Schottky barrier heights of metal-MoS₂ contacts to devices fabricated from CVD synthesized MoS₂ films were reduced by inserting a thin tunneling Ta₂O₅ layer between MoS₂ and metal contacts. Schottky barrier height reductions directly correlate with exponential reductions in contact resistance. Over two hundred devices were tested and contact resistances extracted for large scale statistical analysis. As compared to metal-MoS₂ Schottky contacts without an insulator layer, the specific contact resistivity has been lowered by up to 3 orders of magnitude and current values increased by 2 orders of magnitude over large area (>4 cm²) films

A General Design Strategy for Block Copolymer Directed Self-Assembly Patterning of Integrated Circuits Contact Holes using an Alphabet Approach

Directed self-assembly (DSA) is a promising lithography candidate for technology nodes beyond 14 nm. Researchers have shown contact hole patterning for random logic circuits using DSA with small physical templates. This paper introduces an alphabet approach that uses a minimal set of small physical templates to pattern all contacts configurations on integrated circuits. We illustrate, through experiments, a general and scalable template design strategy that links the DSA material properties to the technology node requirements

HfO_x‑Based Vertical Resistive Switching Random Access Memory Suitable for Bit-Cost-Effective Three-Dimensional Cross-Point Architecture

The three-dimensional (3D) cross-point array architecture is attractive for future ultra-high-density nonvolatile memory application. A bit-cost-effective technology path toward the 3D integration that requires only one critical lithography step or mask for reducing the bit-cost is demonstrated in this work. A double-layer HfO_x-based vertical resistive switching random access memory (RRAM) is fabricated and characterized. The HfO_x thin film is deposited at the sidewall of the predefined trench by atomic layer deposition, forming a vertical memory structure. Electrode/oxide interface engineering with a TiON interfacial layer results in nonlinear <i>I</i>–<i>V</i> suitable for the selectorless array. The fabricated HfO_x vertical RRAM shows excellent performances such as reset current (<50 μA), switching speed (<100 ns), switching endurance (>10⁸ cycles), read disturbance immunity (>10⁹ cycles), and data retention time (>10⁵ s @ 125 °C)

High-Performance p‑Type Black Phosphorus Transistor with Scandium Contact

A record high current density of 580 μA/μm is achieved for long-channel, few-layer black phosphorus transistors with scandium contacts after 400 K vacuum annealing. The annealing effectively improves the on-state current and <i>I</i>_on/<i>I</i>_off ratio by 1 order of magnitude and the subthreshold swing by ∼2.5×, whereas Al₂O₃ capping significantly degrades transistor performances, resulting in 5× lower on-state current and 3× lower <i>I</i>_on/<i>I</i>_off ratio. The influences of moisture on black phosphorus metal contacts are elucidated by analyzing the hysteresis of 3–20 nm thick black phosphorus transistors with scandium and gold contacts under different conditions: as-fabricated, after vacuum annealing, and after Al₂O₃ capping. The optimal black phosphorus film thickness for transistors with scandium contacts is found to be ∼10 nm. Moreover, p-type performance is shown in all transistors with scandium contacts, suggesting that the Fermi level is pinned closer to the valence band regardless of the flake thickness

Engineering a Large Scale Indium Nanodot Array for Refractive Index Sensing

In this work, we developed a simple method to fabricate 12 × 4 mm² large scale nanostructure arrays and investigated the feasibility of indium nanodot (ND) array with different diameters and periods for refractive index sensing. Absorption resonances at multiple wavelengths from the visible to the near-infrared range were observed for various incident angles in a variety of media. Engineering the ND array with a centered square lattice, we successfully enhanced the sensitivity by 60% and improved the figure of merit (FOM) by 190%. The evolution of the resonance dips in the reflection spectra, of square lattice and centered square lattice, from air to water, matches well with the results of Lumerical FDTD simulation. The improvement of sensitivity is due to the enhancement of local electromagnetic field (E-field) near the NDs with centered square lattice, as revealed by E-field simulation at resonance wavelengths. The E-field is enhanced due to coupling between the two square ND arrays with 2x period at phase matching. This work illustrates an effective way to engineer and fabricate a refractive index sensor at a large scale. This is the first experimental demonstration of poor-metal (indium) nanostructure array for refractive index sensing. It also demonstrates a centered square lattice for higher sensitivity and as a better basic platform for more complex sensor designs