Experimental comparison of four nonlinear magnetic detection methods and considerations on clinical usability.

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising for clinical applications, because they have a characteristic nonlinear magnetic response when an external magnetic field is applied. This nonlinearity enables the distinct detection of SPIONs and makes measurements less sensitive to the human body and surgical steel instruments. In clinical applications, only a limited field strength for the magnetic detection is allowed. The signal to noise ratios (SNRs) of four nonlinear magnetic detection methods are compared. These methods include differential magnetometry and three variations of magnetic particle spectroscopy: frequency mixing, second harmonic detection and third harmonic detection. All methods were implemented on the same hardware and experimentally compared for various field strengths. To make the comparison fair, the same power was supplied to the excitation coil each time. In general, the SNR increases with increasing field strength. The SNR per drive field of all methods stabilizes or even decreases for field strengths above 6 mT. The second harmonic detection has the best SNR and the most room for improvement.

Direct coupling of a free-flow isotachophoresis (FFITP) device with electrospray ionization mass spectrometry (ESI-MS).

We present the online coupling of a free-flow isotachophoresis (FFITP) device to an electrospray ionization mass spectrometer (ESI-MS) for continuous analysis without extensive sample preparation. Free-flow-electrophoresis techniques are used for continuous electrophoretic separations using an electric field applied perpendicular to the buffer and sample flow, with FFITP using a discontinuous electrolyte system to concurrently focus a target analyte and remove interferences. The online coupling of FFITP to ESI-MS decouples the separation and detection timeframe because the electrophoretic separation takes place perpendicular to the flow direction, which can be beneficial for monitoring (bio)chemical changes and/or extensive MS(n) studies. We demonstrated the coupling of FFITP with ESI-MS for simultaneous concentration of target analytes and sample clean-up. Furthermore, we show hydrodynamic control of the fluidic fraction injected into the MS, allowing for fluidically controlled scanning of the ITP window. Future applications of this approach are expected in monitoring biochemical changes and proteomics.

Cantilever arrays with self-aligned nanotips of uniform height.

Cantilever arrays are employed to increase the throughput of imaging and manipulation at the nanoscale. We present a fabrication process to construct cantilever arrays with nanotips that show a uniform tip-sample distance. Such uniformity is crucial, because in many applications the cantilevers do not feature individual tip-sample spacing control. Uniform cantilever arrays lead to very similar tip-sample interaction within an array, enable non-contact modes for arrays and give better control over the load force in contact modes. The developed process flow uses a single mask to define both tips and cantilevers. An additional mask is required for the back side etch. The tips are self-aligned in the convex corner at the free end of each cantilever. Although we use standard optical contact lithography, we show that the convex corner can be sharpened to a nanometre scale radius by an isotropic underetch step. The process is robust and wafer-scale. The resonance frequencies of the cantilevers within an array are shown to be highly uniform with a relative standard error of 0.26% or lower. The tip-sample distance within an array of up to ten cantilevers is measured to have a standard error around 10 nm. An imaging demonstration using the AFM shows that all cantilevers in the array have a sharp tip with a radius below 10 nm. The process flow for the cantilever arrays finds application in probe-based nanolithography, probe-based data storage, nanomanufacturing and parallel scanning probe microscopy.

Force modulation for enhanced nanoscale electrical sensing.

Scanning probe microscopy employing conductive probes is a powerful tool for the investigation and modification of electrical properties at the nanoscale. Application areas include semiconductor metrology, probe-based data storage and materials research. Conductive probes can also be used to emulate nanoscale electrical contacts. However, unreliable electrical contact and tip wear have severely hampered the widespread usage of conductive probes for these applications. In this paper we introduce a force modulation technique for enhanced nanoscale electrical sensing using conductive probes. This technique results in lower friction, reduced tip wear and enhanced electrical contact quality. Experimental results using phase-change material stacks and platinum silicide conductive probes clearly demonstrate the efficacy of the proposed technique. Furthermore, conductive-mode imaging experiments on specially prepared platinum/carbon samples are presented to demonstrate the widespread applicability of this technique.

Parallel optical readout of cantilever arrays in dynamic mode.

Parallel frequency readout of an array of cantilevers is demonstrated using optical beam deflection with a single laser-diode pair. Multi-frequency addressing makes the individual nanomechanical response of each cantilever distinguishable within the received signal. Addressing is accomplished by exciting the array with the sum of all cantilever resonant frequencies. This technique requires considerably less hardware compared to other parallel optical readout techniques. Readout is demonstrated in beam deflection mode and interference mode. Many cantilevers can be readout in parallel, limited by the oscillators' quality factor and available bandwidth. The proposed technique facilitates parallelism in applications at the nano-scale, including probe-based data storage and biological sensing.

Thermally induced switching field distribution of a single CoPt dot in a large array.

Magnetic dot arrays with perpendicular magnetic anisotropy were fabricated by patterning Co(80)Pt(20)-alloy continuous films by means of laser interference lithography. As commonly seen in large dot arrays, there is a large difference in the switching field between dots. Here we investigate the origin of this large switching field distribution, by using the anomalous Hall effect (AHE). The high sensitivity of the AHE permits us to measure the magnetic reversal of individual dots in an array of 80 dots with a diameter of 180 nm. By taking 1000 hysteresis loops we reveal the thermally induced switching field distribution SFD(T) of individual dots inside the array. The SFD(T) of the first and last switching dots were fitted to an Arrhenius model, and a clear difference in switching volume and magnetic anisotropy was observed between dots switching at low and high fields.