ABSTRACT
One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument ("smart nanoscalpel") at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the "Nanoscalpel" in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a "smart nanoscalpel" is practical for the microsurgery of malignant neoplasms.
ABSTRACT
Copper-doped titanium oxynitride (TiNxOy) thin films were grown by atomic layer deposition (ALD) using the TiCl4 precursor, NH3, and O2 at 420 °C. Forming gas was used to reduce the background oxygen concentration and to transfer the copper atoms in an ALD chamber prior to the growth initiation of Cu-doped TiNxOy. Such forming gas-mediated Cu-doping of TiNxOy films had a pronounced effect on their resistivity, which dropped from 484 ± 8 to 202 ± 4 µΩ cm, and also on the resistance temperature coefficient (TCR), which decreased from 1000 to 150 ppm °C-1. We explored physical mechanisms causing this reduction by performing comparative analysis of atomic force microscopy, X-ray photoemission spectroscopy, X-ray diffraction, optical spectra, low-temperature transport, and Hall measurement data for the samples grown with and without forming gas doping. The difference in the oxygen concentration between the films did not exceed 6%. Copper segregated to the TiNxOy surface where its concentration reached 0.72%, but its penetration depth was less than 10 nm. Pronounced effects of the copper doping by forming gas included the TiNxOy film crystallite average size decrease from 57-59 to 32-34 nm, considerably finer surface granularity, electron concentration increase from 2.2(3) × 1022 to 3.5(1) × 1022 cm-3, and the electron mobility improvement from 0.56(4) to 0.92(2) cm2 V-1 s-1. The DC resistivity versus temperature R(T) measurements from 4.2 to 300 K showed a Cu-induced phase transition from a disordered to semimetallic state. The resistivity of Cu-doped TiNxOy films decreased with the temperature increase at low temperatures and reached the minimum near T = 50 K revealing signatures of the quantum interference effects similar to 2D Cu thin films, and then, semimetallic behavior was observed at higher temperatures. In TiNxOy films grown without forming gas, the resistivity decreased with the temperature increase as R(T) = - 1.88T0.6 + 604 µΩ cm with no semimetallic behavior observed. The medium range resistivity and low TCR of Cu-doped TiNxOy make this material an attractive choice for improved matching resistors in RF analog circuits and Si complementary metal-oxide-semiconductor integrated circuits.