Ultralow Energy Consumption Angstrom-Fluidic Memristor.

The emergence of nanofluidic memristors has made a giant leap to mimic the neuromorphic functions of biological neurons. Here, we report neuromorphic signaling using Angstrom-scale funnel-shaped channels with poly-l-lysine (PLL) assembled at nano-openings. We found frequency-dependent current-voltage characteristics under sweeping voltage, which represents a diode in low frequencies, but it showed pinched current hysteresis as frequency increases. The current hysteresis is strongly dependent on pH values but weakly dependent on salt concentration. We attributed the current hysteresis to the entropy barrier of PLL molecules entering and exiting the Angstrom channels, resulting in reversible voltage-gated open-close state transitions. We successfully emulated the synaptic adaptation of Hebbian learning using voltage spikes and obtained a minimum energy consumption of 2-23 fJ in each spike per channel. Our findings pave a new way to mimic neuronal functions by Angstrom channels in low energy consumption.

High turnover and rescue effect of XRCC1 in response to heavy charged particle radiation.

The DNA damage response is a highly orchestrated process. The involvement of the DNA damage response factors in DNA damage response depends on their biochemical reactions with each other and with chromatin. Using online live-cell imaging combined with heavy ion microbeam irradiation, we studied the response of the scaffold protein X-ray repair cross-complementary protein 1 (XRCC1) at the localized DNA damage in charged particle irradiated HT1080 cells expressing XRCC1-tagged RFP. The results showed that XRCC1 was recruited to the DNA damage with ultrafast kinetics in a poly ADP-ribose polymerase-dependent manner. The consecutive reaction model well explained the response of XRCC1 at ion hits, and we found that the XRCC1 recruitment was faster and dissociation was slower in the G2 phase than those in the G1 phase. The fractionated irradiation of the same cells resulted in accelerated dissociation at the previous damage sites, and the dissociated XRCC1 immediately recycled with a higher recruitment efficiency. Our data revealed XRCC1's new rescue mechanism and its high turnover in DNA damage response, which benefits our understanding of the biochemical mechanism in DNA damage response.

Temperature Induced Dimensional Tuning and Anomalous Deformation of Micro/Nanopores.

Artificial nanopores have become a common toolbox in nanotechnologies, with dimension and geometry as predominant factors. Most fabrication technologies determine the pore size beforehand, but few exist that enable size-tuning post-manufacturing. In this work, we reported a type of ion track etched micro/nanopores on uniaxially drawn PET foils that enable irreversible thermal shrinkage, thus tuning the pore dimensions by increasing ambient temperatures. Importantly, we found a complex pore deformation process, which for a specific range of pore sizes and temperatures resulted in a peculiar "eye"-shaped appearance of the pore openings. We analyzed the mechanical stresses and theoretically illustrated the complex deformation process by a phase diagram. Temperature-induced dimensional tuning nanopores reduced maximally over 98% of ionic conduction in a single nanopore and 99% of pressure-driven flow in a pore-array membrane within few seconds at 90 °C, which is useful for temperature-modulated mass transport in nanotechnology and energy applications.

Sub-5 nm Lithography with Single GeV Heavy Ions Using Inorganic Resist.

In this work, we demonstrate a process having the capability to realize single-digit nanometer lithography using single heavy ions. By adopting 2.15 GeV 86Kr26+ ions as the exposure source and hydrogen silsesquioxane (HSQ) as a negative-tone inorganic resist, ultrahigh-aspect-ratio nanofilaments with sub-5 nm feature size, following the trajectory of single heavy ions, were reliably obtained. Control experiments and simulation analysis indicate that the high-resolution capabilities of both HSQ resist and the heavy ions contribute the sub-5 nm fabrication result. Our work on the one hand provides a robust evidence that single heavy ions have the potential for single-digit nanometer lithography and on the other hand proves the capability of inorganic resists for reliable sub-5 nm patterning. Along with the further development of heavy-ion technology, their ultimate patterning resolution is supposed to be more accessible for device prototyping and resist evaluation at the single-digit nanometer scale.

Nanofluidic memristor based on the elastic deformation of nanopores with nanoparticle adsorption.

The memristor is the building block of neuromorphic computing. We report a new type of nanofluidic memristor based on the principle of elastic strain on polymer nanopores. With nanoparticles absorbed at the wall of a single conical polymer nanopore, we find a pinched hysteresis of the current within a scanning frequency range of 0.01-0.1 Hz, switching to a diode below 0.01 Hz and a resistor above 0.1 Hz. We attribute the current hysteresis to the elastic strain at the tip side of the nanopore, caused by electrical force on the particles adsorbed at the inner wall surface. Our simulation and analytical equations match well with experimental results, with a phase diagram for predicting the system transitions. We demonstrate the plasticity of our nanofluidic memristor to be similar to a biological synapse. Our findings pave a new way for ionic neuromorphic computing using nanofluidic memristors.

Double-sided plasmonic metasurface for simultaneous biomolecular separation and SERS detection.

Porous membrane-based nanofiltration separation of small biomolecules is a widely used biotechnology for which size-based selectivity is a critical parameter of technological relevance. Efficient determination of size selectivity calls for an advanced detection method capable of performing sensitive, rapid, and on-membrane examination. Surface-enhanced Raman spectroscopy (SERS) is such a detection method that has been widely recognized as an ultrasensitive technique for trace-level detection with sensitivity down to the single-molecule level. In this work, we for the first time develop a double-sided hierarchical porous membrane-like plasmonic metasurface to realize high-selectivity bimolecular separation and simultaneous ultrasensitive SERS detection. This highly flexible device, consisting of subwavelength nanocone pairs surrounded by randomly orientated sub-5 nm nanogrooves, was prepared by combining customized "top-down" fabrication of conical nanopores in an ion-track registered polycarbonate membrane and self-assembly of nanogrooves on the membrane surface through physical vapor deposition. The unique tip-to-tip oriented conical nanopores in the device enables excellent size-based molecular selectivity; the hierarchical groove-pore structure supports a peculiar cascaded electromagnetic near-field enhancement mechanism, endowing the device with SERS-based molecular detection of ultrahigh sensitivity, uniformity, repeatability, and polarization independence. With such dual structural merits and performance enhancement, we demonstrate effective nanofiltration separation of small-sized adenine from big-sized ss-DNA and synergistic SERS determination of their species. We experimentally demonstrate an ultrasensitive detection of 4-mercaptopyridine down to 10 pM. Together with its unparalleled mechanical flexibility, this double-side-responsive plasmonic metasurface membrane can find great potential in real-world molecular filtration and detection under extremely complex working conditions.

Multifunctional graphene heterogeneous nanochannel with voltage-tunable ion selectivity.

Ion-selective nanoporous two-dimensional (2D) materials have shown extraordinary potential in energy conversion, ion separation, and nanofluidic devices; however, different applications require diverse nanochannel devices with different ion selectivity, which is limited by sample preparation and experimental techniques. Herein, we develop a heterogeneous graphene-based polyethylene terephthalate nanochannel (GPETNC) with controllable ion sieving to overcome those difficulties. Simply by adjusting the applied voltage, ion selectivity among K+, Na+, Li+, Ca2+, and Mg2+ of the GPETNC can be immediately tuned. At negative voltages, the GPETNC serves as a mono/divalent ion selective device by impeding most divalent cations to transport through; at positive voltages, it mimics a biological K+ nanochannel, which conducts K+ much more rapidly than the other ions with K+/ions selectivity up to about 4.6. Besides, the GPETNC also exhibits the promise as a cation-responsive nanofluidic diode with the ability to rectify ion currents. Theoretical calculations indicate that the voltage-dependent ion enrichment/depletion inside the GPETNC affects the effective surface charge density of the utilized graphene subnanopores and thus leads to the electrically controllable ion sieving. This work provides ways to develop heterogeneous nanochannels with tunable ion selectivity toward broad applications.

High-Performance Osmotic Power Generators Based on the 1D/2D Hybrid Nanochannel System.

Extracting clean energy by converting the salinity gradient between river and sea into energy is an effective way to reduce the global pollution and carbon emissions. Reverse electrodialysis (RED) is of great importance to realize the energy conversion assisting the ion-selective membrane. However, its higher ion resistance and lower conversion efficiency results in the undesirable power conversion performance. Here, we demonstrate a 1D/2D hybrid nanochannel system to achieve high osmotic energy conversion and output power. This heterogeneous structure is composed of two structures, in which the subnanometer nanochannels in graphene oxide membrane (GOM) can serve as a selective layer and reduce the ion diffusion energy barrier, while the nanochannel in the polymer can introduce asymmetry to enhance ionic rectification and conversion efficiency. This heterogeneous membrane exhibits excellent cation selectivity and enhanced ionic current rectification (ICR) performance. The application of the GOM/PET hybrid nanochannel system in osmotic energy harvesting is evaluated, and the output power can reach up to 118.2 pW with the energy conversion efficiency of 40.3%. Theoretical calculation indicates that the 1D/2D hybrid system can effectively take the advantage of excellent cation selectivity of 2D lamellar nanochannels to improve its RED performance significantly.

Scanning irradiation device for mice in vivo with pulsed and continuous proton beams.

A technical set-up for irradiation of subcutaneous tumours in mice with nanosecond-pulsed proton beams or continuous proton beams is described and was successfully used in a first experiment to explore future potential of laser-driven particle beams, which are pulsed due to the acceleration process, for radiation therapy. The chosen concept uses a microbeam approach. By focusing the beam to approximately 100 × 100 µm(2), the necessary fluence of 10(9) protons per cm(2) to deliver a dose of 20 Gy with one-nanosecond shot in the Bragg peak of 23 MeV protons is achieved. Electrical and mechanical beam scanning combines rapid dose delivery with large scan ranges. Aluminium sheets one millimetre in front of the target are used as beam energy degrader, necessary for adjusting the depth-dose profile. The required procedures for treatment planning and dose verification are presented. In a first experiment, 24 tumours in mice were successfully irradiated with 23 MeV protons and a single dose of 20 Gy in pulsed or continuous mode with dose differences between both modes of 10%. So far, no significant difference in tumour growth delay was observed.

Nanoscale insight into chromatin remodeling and DNA repair complex in HeLa cells after ionizing radiation.

The dynamic structure of nuclear chromatin and its regulation in the formation of repair complex is essential in DNA damage response and repair. Using single molecule localization microscopy STORM this work discovered that the nuclear chromatin organization was relaxed from 200 to 400 nm thick irregular frame and remodeled to dispersed sub-100 nm structure in HeLa cells after X-ray irradiation. The DSB repair factors (γ-H2AX, MDC1, 53BP1) showed distribution as microscale-colocalized and nanoscale interlaced substructure in the DSB repair complex. The dual-color nanoscopic imaging of γ-H2AX and chromatin at the DSB sites suggest that DNA damage response and repair cascade are chromatin structure-dependent and also partly dependent on the distance to the DSB sites. The sub-100 nm structure of fibers and nanoclusters of the relaxed nuclear chromatin and the DSB repair factors highly resembled the cross-section view of chromatin organization. These data demonstrated the polymorphic and dynamic behavior of the chromatin organization in vivo, and provided nanoscale insight into the interplay between chromatin remodeling and DNA damage response and DNA repair.

Bioinspired Dual-Responsive Nanofluidic Diodes by Poly-l-lysine Modification.

A smart nanofluidic device attracts attention as it enables to control the physicochemical properties and transportation phenomena, by using stimuli-responsive materials. This work reports a bioinspired modification of a conical ion track-etched polyethylene terephthalate nanopore surface by coating a layer of poly-l-lysine (PLL), which is a commonly used coating in biotechnology to achieve a dual-responsive nanofluidic channel by pH or temperature. The rectification of ionic transportation can be reversed by assembling PLL because of the change of surface bonds from the carboxyl to amine group. The PLL-modified nanopore becomes nonconductive as an "OFF" state at pH 11.5 and at a temperature of 70 °C in solution. The ionic transport in nanopores can be switched to the "ON" (conductive) state, by either decreasing pH or temperature. The transitions between "ON" and "OFF" states present excellent reversibility, which make the PLL-modified nanopores a promising smart nanofluidic device that can be used for drug delivery or biomimic ion/mass transport in future, besides the good biocompatibility and ease of use of PLL modification.

Electrical Field Regulation of Ion Transport in Polyethylene Terephthalate Nanochannels.

Rectified ion transport in nanochannels is the basis of ion channels in biological cells and has inspired emerging nanochannel applications in ion separation, Coulter counters, and biomolecule detection and nanochannel energy harvesters. In this work we fabricated a polyethylene terephthalate (PET) conical nanochannel using latent ion track etching technique and then systematically studied the ion transport and influence of cation species on the nanochannel surface with cyclic I-V measurement. We discovered the electrical regulation of the reversible and irreversible modification of the nanochannel transportation by bivalent and trivalent cations, revealing the existence of the switching threshold voltage which can control the current rectification in bivalent solution. The proposed mechanism of the transport state transition in the PET nanochannel mimics behaviors of voltage-gated biological ion channels. These findings provide new insight into the understanding of the ion channel signaling and translocation control of charged particles in nanochannel applications.

The absence of an early calcium response to heavy-ion radiation in Mammalian cells.

Intracellular calcium is an important second messenger that regulates many cell functions. Recent studies have shown that calcium ions can also regulate the cellular responses to ionizing radiation. However, previous data are restricted to cells treated with low-LET radiations (X rays, gamma rays and beta particles). In this work, we investigated the calcium levels in cells exposed to heavy-ion radiation of high LET. The experiments were performed at the single ion hit facility of the GSI heavy-ion microprobe. Using a built-in online calcium imaging system, the intracellular calcium concentrations were examined in HeLa cells and human foreskin fibroblast AG1522-D cells before and after irradiation with 4.8 MeV/nucleon carbon or argon ions. Although the experiment was sensitive enough to detect the calcium response to other known stimuli, no response to heavy-ion radiation was found in these two cell types. We also found that heavy-ion radiation has no impact on calcium oscillation induced by hypoxia stress in fibroblast cells.

Ultrafast ion sieving using nanoporous polymeric membranes.

The great potential of nanoporous membranes for water filtration and chemical separation has been challenged by the trade-off between selectivity and permeability. Here we report on nanoporous polymer membranes with an excellent balance between selectivity and permeability of ions. Our membranes are fabricated by irradiating 2-µm-thick polyethylene terephthalate Lumirror® films with GeV heavy ions followed by ultraviolet exposure. These membranes show a high transport rate of K+ ions of up to 14 mol h-1 m-2 and a selectivity of alkali metal ions over heavy metal ions of >500. Combining transport experiments and molecular dynamics simulations with a polymeric nanopore model, we demonstrate that the high permeability is attributable to the presence of nanopores with a radius of ~0.5 nm and a density of up to 5 × 1010 cm-2, and the selectivity is ascribed to the interaction between the partially dehydrated ions and the negatively charged nanopore wall.

Live cell imaging combined with high-energy single-ion microbeam.

DNA strand breaks can lead to cell carcinogenesis or cell death if not repaired rapidly and efficiently. An online live cell imaging system was established at the high energy microbeam facility at the Institute of Modern Physics to study early and fast cellular response to DNA damage after high linear energy transfer ion radiation. The HT1080 cells expressing XRCC1-RFP were irradiated with single high energy nickel ions, and time-lapse images of the irradiated cells were obtained online. The live cell imaging analysis shows that strand-break repair protein XRCC1 was recruited to the ion hit position within 20 s in the cells and formed bright foci in the cell nucleus. The fast recruitment of XRCC1 at the ion hits reached a maximum at about 200 s post-irradiation and then was followed by a slower release into the nucleoplasm. The measured dual-exponential kinetics of XRCC1 protein are consistent with the proposed consecutive reaction model, and the measurements obtained that the reaction rate constant of the XRCC1 recruitment to DNA strand break is 1.2 × 10(-3) s(-1) and the reaction rate constant of the XRCC1 release from the break-XRCC1 complex is 1.2 × 10(-2) s(-1).

Study on the bias-dependent effects of proton-induced damage in CdZnTe radiation detectors using ion beam induced charge microscopy.

The influence of damage induced by 2MeV protons on CdZnTe radiation detectors is investigated using ion beam induced charge (IBIC) microscopy. Charge collection efficiency (CCE) in irradiated region is found to be degraded above a fluence of 3.3×10(11)p/cm(2) and the energy spectrum is severely deteriorated with increasing fluence. Moreover, CCE maps obtained under the applied biases from 50V to 400V suggests that local radiation damage results in significant degradation of CCE uniformity, especially under low bias, i. e., 50V and 100V. The CCE nonuniformity induced by local radiation damage, however, can be greatly improved by increasing the detector applied bias. This bias-dependent effect of 2MeV proton-induced radiation damage in CdZnTe detectors is attributed to the interaction of electron cloud and radiation-induced displacement defects.

Effects of magnesium on the performance of sows and their piglets.

The objective of this study was to evaluate the effects of supplemental magnesium (Mg) on the performance of gilts and parity 3 sows and their piglets. Fifty-six gilts (Trial 1) and 56 sows (Trial 2) were assigned to one of 4 treatments according to their mating weight, respectively. The treatments comprised corn-soybean meal based gestation and lactation diets (0.21% magnesium) supplemented with 0, 0.015, 0.03, or 0.045% Mg from mating until weaning. The results showed that magnesium supplementation significantly (P < 0.05) reduced the weaning to estrus interval in both gilts and sows. There were significant effects (P < 0.05) of supplemental magnesium on the total number of piglets born, born alive and weaned in sows. In late gestation and lactation, the digestibility of crude fiber (quadratic effects, P < 0.05), and crude protein (P < 0.05), were significantly influenced by magnesium in gilts and sows, respectively. There were differences among the 4 groups in terms of the apparent digestibility of dry matter and crude fiber in sows (P < 0.05) during both early and late gestation. The apparent digestibility of gross energy was increased for sows in late gestation (P < 0.05), and lactation (quadratic effects, P < 0.05). At farrowing and weaning, serum prolactin levels and alkaline phosphate activities linearly increased in sows as the Mg supplementation increased (P < 0.05). Serum Mg of sows at farrowing and serum urea nitrogen of sows at weaning was significantly influenced by Mg supplementation (P < 0.05). The Mg concentration in sow colostrum and the serum of their piglets were increased by supplemental magnesium (P < 0.05). In addition, growth hormone levels were linearly elevated (P < 0.05) in the serum of piglets suckling sows. Our data demonstrated that supplemental magnesium has the potential to improve the reproduction performance of sows, and the suitable supplemental dose ranged from 0.015% to 0.03%.

Focusing giga-electronvolt heavy ions to micrometers at the Institute of Modern Physics.

To study the radiation effect of cosmic heavy ions of low fluxes in electronics and living samples, a focusing heavy ion microbeam facility, for ions with energies of several MeV/u up to 100 MeV/u, was constructed in the Institute of Modern Physics of the Chinese Academy of Sciences. This facility has a vertical design and an experiment platform for both in-vacuum analysis and in-air irradiation. Recently, microbeam of (12)C(6+) with energy of 80.55 MeV/u was successfully achieved at this interdisciplinary microbeam facility with a full beam spot size of 3 µm × 5 µm on target in air. Different from ions with energy of several MeV/u, the very high ion energy of hundred MeV/u level induces problems in beam micro-collimation, online beam spot diagnosis, radiation protection, etc. This paper presents the microbeam setup, difficulties in microbeam formation, and the preliminary experiments performed with the facility.

Spatial dynamics of DNA damage response protein foci along the ion trajectory of high-LET particles.

High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial development of γ-H2AX, 53BP1 and phospho-NBS1 foci in BJ1-hTERT cells irradiated with 55 MeV carbon ions and compared the results with the dynamics of double-strand break (DSB) distributions simulated using the PARTRAC model. Clusters consisting of several foci were observed along the ion trajectory after irradiation. The spatial dynamics of the protein foci supports that the foci clusters are not formed by neighboring foci but instead originate from the DSB cluster damage induced by high-LET radiations.