Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer.

BACKGROUND: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer). RESULTS: In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients. CONCLUSIONS: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.

Long-range vortex transfer in superconducting nanowires.

Under high-enough values of perpendicularly-applied magnetic field and current, a type-II superconductor presents a finite resistance caused by the vortex motion driven by the Lorentz force. To recover the dissipation-free conduction state, strategies for minimizing vortex motion have been intensely studied in the last decades. However, the non-local vortex motion, arising in areas depleted of current, has been scarcely investigated despite its potential application for logic devices. Here, we propose a route to transfer vortices carried by non-local motion through long distances (up to 10 micrometers) in 50 nm-wide superconducting WC nanowires grown by Ga+ Focused Ion Beam Induced Deposition. A giant non-local electrical resistance of 36 Ω has been measured at 2 K in 3 µm-long nanowires, which is 40 times higher than signals reported for wider wires of other superconductors. This giant effect is accounted for by the existence of a strong edge confinement potential that hampers transversal vortex displacements, allowing the long-range coherent displacement of a single vortex row along the superconducting channel. Experimental results are in good agreement with numerical simulations of vortex dynamics based on the time-dependent Ginzburg-Landau equations. Our results pave the way for future developments on information technologies built upon single vortex manipulation in nano-superconductors.

Three-Axis Vector Nano Superconducting Quantum Interference Device.

We present the design, realization, and performance of a three-axis vector nano superconducting quantum interference device (nanoSQUID). It consists of three mutually orthogonal SQUID nanoloops that allow distinguishing the three components of the vector magnetic moment of individual nanoparticles placed at a specific position. The device is based on Nb/HfTi/Nb Josephson junctions and exhibits line widths of ∼250 nm and inner loop areas of 600 × 90 and 500 × 500 nm(2). Operation at temperature T = 4.2 K under external magnetic fields perpendicular to the substrate plane up to ∼50 mT is demonstrated. The experimental flux noise below [Formula: see text] in the white noise limit and the reduced dimensions lead to a total calculated spin sensitivity of [Formula: see text] and [Formula: see text] for the in-plane and out-of-plane components of the vector magnetic moment, respectively. The potential of the device for studying three-dimensional properties of individual nanomagnets is discussed.

Screen-printed nanoparticles as anti-counterfeiting tags.

Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors.

Thickness-modulated tungsten-carbon superconducting nanostructures grown by focused ion beam induced deposition for vortex pinning up to high magnetic fields.

We report efficient vortex pinning in thickness-modulated tungsten-carbon-based (W-C) nanostructures grown by focused ion beam induced deposition (FIBID). By using FIBID, W-C superconducting films have been created with thickness modulation properties exhibiting periodicity from 60 to 140 nm, leading to a strong pinning potential for the vortex lattice. This produces local minima in the resistivity up to high magnetic fields (2.2 T) in a broad temperature range due to commensurability effects between the pinning potential and the vortex lattice. The results show that the combination of single-step FIBID fabrication of superconducting nanostructures with built-in artificial pinning landscapes and the small intrinsic random pinning potential of this material produces strong periodic pinning potentials, maximizing the opportunities for the investigation of fundamental aspects in vortex science under changing external stimuli (e.g., temperature, magnetic field, electrical current).

Heterodimetallic [LnLn'] lanthanide complexes: toward a chemical design of two-qubit molecular spin quantum gates.

A major challenge for realizing quantum computation is finding suitable systems to embody quantum bits (qubits) and quantum gates (qugates) in a robust and scalable architecture. An emerging bottom-up approach uses the electronic spins of lanthanides. Universal qugates may then be engineered by arranging in a molecule two interacting and different lanthanide ions. Preparing heterometallic lanthanide species is, however, extremely challenging. We have discovered a method to obtain [LnLn'] complexes with the appropriate requirements. Compound [CeEr] is deemed to represent an ideal situation. Both ions have a doubly degenerate magnetic ground state and can be addressed individually. Their isotopes have mainly zero nuclear spin, which enhances the electronic spin coherence. The analogues [Ce2], [Er2], [CeY], and [LaEr] have also been prepared to assist in showing that [CeEr] meets the qugate requirements, as revealed through magnetic susceptibility, specific heat, and EPR. Molecules could now be used for quantum information processing.

Mn12 single molecule magnets deposited on µ-SQUID sensors: the role of interphases and structural modifications.

Direct measurements of the linear ac susceptibility and magnetic relaxation of a few Mn12 monolayers deposited on a µ-SQUID sensor are reported. In order to integrate the molecules into the device, DPN has been the technique of choice. It enabled the structuration of the molecules on the most sensitive areas of the sensor without the need for any previous functionalization of the molecule or the substrate, while controlling the number of molecular units deposited on each array. The measurements reveal that their characteristic SMM behaviour is lost, a fact that is attributed to molecular distortions originated by the strong surface tensions arising at the molecular interphases.

Surface-confined molecular coolers for cryogenics.

An excellent molecule-based cryogenic magnetic refrigerant, gadolinium acetate tetrahydrate, is here used to decorate selected portions of silicon substrate. By quantitative magnetic force microscopy for a variable applied magnetic field near liquid-helium temperature, the molecules are demonstrated to hold their magnetic properties intact, and therefore their cooling functionality, after their deposition. These results represent a step forward towards the realization of a molecule-based micro-refrigerating device at very low temperatures.

Fragmenting gadolinium: mononuclear polyoxometalate-based magnetic coolers for ultra-low temperatures.

The polyoxometalate clusters with formula [Gd(W(5) O(18) )(2) ](9-) and [Gd(P(5) W(30) O(110) )](12-) each carry a single magnetic ion of gadolinium, which is the most widespread element among magnetic refrigerant materials. In an adiabatic demagnetization, the lowest attainable temperature is limited by the presence of magnetic interactions that bring about magnetic order below a critical temperature. We demonstrate that this limitation can be overcome by chemically engineering the molecules in such a way to effectively screen all magnetic interactions, suggesting their use as ultra-low-temperature coolers.

Nanoscale positioning of inorganic nanoparticles using biological ferritin arrays fabricated by dip-pen nanolithography.

In this manuscript we demonstrate the spatially controlled immobilization of ferritin proteins by directly writing them on a wide range of substrates of technological interest. Optical and fluorescence microscopy, AFM and TOF-SIMS studies confirm the successful deposition of the protein on those surfaces. Control on nanostructure shape and size, by miniaturizing the dot-like features down to a 100 nm, demonstrates the particular capabilities of the DPN approach. Ultimately, this study gives the opportunity to design nanoparticle-based arrays regarding the growing interest in the use of nanoparticles as structural and functional elements for fabricating nanodevices. Herein, we demonstrate how the protein shell of ferritins can be removed by a simple heat-treatment process while maintaining the encapsulated inorganic nanoparticle intact on the same location of the nanoarray. As a result, this study establishes how direct-write DPN approach could give the opportunity to design not only protein-based nanoarrays but also nanoparticle-based nanoarrays with high-resolution and control.