Fredrik Öisjöen

A new approach for bioassays based on frequency- and time-domain measurements of magnetic nanoparticles

We demonstrate a one-step wash-free bioassay measurement system capable of tracking biochemical binding events. Our approach combines the high resolution of frequency- and high speed of time-domain measurements in a single device in combination with a fast one-step bioassay. The one-step nature of our magnetic nanoparticle (MNP) based assay reduces the time between sample extraction and quantitative results while mitigating the risks of contamination related to washing steps. Our method also enables tracking of binding events, providing the possibility of, for example, investigation of how chemical/biological environments affect the rate of a binding process or study of the action of certain drugs. We detect specific biological binding events occurring on the surfaces of fluid-suspended MNPs that modify their magnetic relaxation behavior. Herein, we extrapolate a modest sensitivity to analyte of 100 ng/ml with the present setup using our rapid one-step bioassay. More importantly, we determine the size-distributions of the MNP systems with theoretical fits to our data obtained from the two complementary measurement modalities and demonstrate quantitative agreement between them.

High-T-c superconducting quantum interference device recordings of spontaneous brain activity: Towards high-T-c magnetoencephalography

We have performed single-and two-channel high transition temperature (high-T-c) superconducting quantum interference device (SQUID) magnetoencephalography (MEG) recordings of spontaneous brain activity in two healthy human subjects. We demonstrate modulation of two well-known brain rhythms: the occipital alpha rhythm and the mu rhythm found in the motor cortex. We further show that despite higher noise-levels compared to their low-T-c counterparts, high-T-c SQUIDs can be used to detect and record physiologically relevant brain rhythms with comparable signal-to-noise ratios. These results indicate the utility of high-T-c technology in MEG recordings of a broader range of brain activity.

Towards an electrowetting-based digital microfluidic platform for magnetic immunoassays

We demonstrate ElectroWetting-On-Dielectric (EWOD) transport and SQUID gradiometer detection of magnetic nanoparticles (MNPs) suspended in a 2 microl de-ionized water droplet. This proof-of-concept methodology constitutes the first development step towards a highly sensitive magnetic immunoassay platform with SQUID readout and droplet-based sample handling. Magnetic AC-susceptibility measurements were performed on MNPs with a hydrodynamic diameter of 100 nm using a high-Tc dc Superconducting Quantum Interference Device (SQUID) gradiometer as detector. We observed that the signal amplitude per unit volume is 2.5 times higher for a 2 microl sample droplet compared to a 30 microl sample volume.

Fast and Sensitive Measurement of Specific Antigen-Antibody Binding Reactions With Magnetic Nanoparticles and HTS SQUID

We have developed an HTS SQUID system for both time and frequency domain measurements of magnetic signals from the Brownian relaxation of liquid-suspended magnetic nanoparticles (MNPs) coated with antibodies. A planar YBa2Cu3O7-x dc SQUID gradiometer with a baseline of 3 mm allows stable operation of the measurement system in an unshielded environment. Agglomeration of MNPs induced by prostate specific antigen-antibody binding complexes is characterized with our system and benchmarked with frequency domain measurements performed by Imego AB using an induction coil magnetometer. We estimate an upper bound for our immunoassay analyte sensitivity of 1.8 ng/radicHz.

High-Tc SQUID gradiometer system for immunoassays

A high-Tc dc SQUID (superconducting quantum interference device) gradiometer was developed for magnetic immunoassays where magnetic nanoparticles are used as markers to detect biological reactions. The gradiometer was fabricated on a 5 × 10 mm2 SrTiO3 bicrystal substrate and has a gradiometer resolution of 2.1 pT cm−1 Hz−1/2. A magnetic signal was detected from a sample of 1 μl of Fe3O4 nanoparticles in a 40 mg ml−1 solution kept in a microcavity fabricated on Si wafers with Si3N4 membranes using MEMS (micro-electro-mechanical-systems) technology. It was found that volumes as small as 0.3 nl in principle would be detectable with our present device. This corresponds to a total number of particles of 2.2 × 107. The estimated average dipole moment per particle is 4.8 × 10−22 Am2. We are aiming at reading out immunoassays by detecting the Brownian relaxation of magnetic nanoparticles, and we also intend to integrate MEMS technology into our system.

Conductive shield for ultra-low-field magnetic resonance imaging: Theory and measurements of eddy currents

Eddy currents induced by applied magnetic-field pulses have been a common issue in ultra-low-field magnetic resonance imaging. In particular, a relatively large prepolarizing field-applied before each signal acquisition sequence to increase the signal-induces currents in the walls of the surrounding conductive shielded room. The magnetic-field transient generated by the eddy currents may cause severe image distortions and signal loss, especially with the large prepolarizing coils designed for in vivo imaging. We derive a theory of eddy currents in thin conducting structures and enclosures to provide intuitive understanding and efficient computations. We present detailed measurements of the eddy-current patterns and their time evolution in a previous-generation shielded room. The analysis led to the design and construction of a new shielded room with symmetrically placed 1.6-mm-thick aluminum sheets that were weakly coupled electrically. The currents flowing around the entire room were heavily damped, resulting in a decay time constant of about 6 ms for both the measured and computed field transients. The measured eddy-current vector maps were in excellent agreement with predictions based on the theory, suggesting that both the experimental methods and the theory were successful and could be applied to a wide variety of thin conducting structures.

Noise properties of high-T-c superconducting flux transformers fabricated using chemical-mechanical polishing

Reproducible high-temperature superconducting multilayer flux transformers were fabricated using chemical mechanical polishing. The measured magnetic field noise of the flip-chip magnetometer based on one such flux transformer with a 9 x 9 mm(2) pickup loop coupled to a bicrystal dc SQUID was 15 fT/Hz(1/2) above 2 kHz. We present an investigation of excess 1/f noise observed at low frequencies and its relationship with the microstructure of the interlayer connections within the flux transformer. The developed high-T-c SQUID magnetometers may be advantageous in ultra-low field magnetic resonance imaging and, with improved low frequency noise, magnetoencephalography applications.

The need for stable, mono-dispersed, and biofunctional magnetic nanoparticles for one-step magnetic immunoassays

We have developed a magnetic immunoassay system (MIA) using magnetic nanoparticle markers for biomolecule detection. We have magnetically characterized multi-core magnetic nanoparticles (MNPs) containing single-domain crystals of Fe3O4 and CoFe2O4 with our system using a high temperature superconducting quantum interference device as detector. We use a Helmholtz coil to excite the MNPs and study the AC-susceptibility. The data is fit to a model and information about the particle size distribution of the MNP system is extracted. We observe high stability of the unfunctionalized MNPs. However, our MIA measurements require stable functionalized MNPs. We have found a significant increase in hydrodynamic size of the functionalized MNP systems in the course of just a few days caused by agglomeration behaviour. Separate measurements performed at Imego AB with their AC-Susceptometer, DynoMAG, confirm these findings. Without stable, functionalized MNPs MIAs of this kind are impossible.

Novel HTS DC squid solutions for NMR applications

We have developed a multilayer flux-transformer-based high-TC SQUID (flip-chip) magnetometer that improves signal-to-noise-ratios (SNR) in ultra-low field magnetic resonance (ulf-MR) recordings of protons in water. Direct ulf-MR-based benchmarking of the flip-chip versus a standard planar high-T C SQUID magnetometer resulted in improvement of the SNR by a factor of 2. This gain is attributable to the improved transformation coefficient (1.9 vs 5.3 nT/Φ0) that increased the signal available to the flip-chip sensor and to the lower noise at the measurement frequency (15 vs 25 fT/Hz1/2 at 4 kHz). The improved SNR can lead to better spectroscopic resolution, lower imaging times, and higher resolution in ulf-MR imaging systems based on high-T C SQUID technology. The experimental details of the sensors, calibration, and ulf-MR benchmarking are presented in this report.

High-T_\mathrm{c} SQUIDs

Superconductivity was discovered by Kamerlingh Onnes in 1911 after he succeeded in liquefying helium. Kamerlingh Onnes discovered that the electrical resistance of mercury vanished when it was cooled to below 4.2 K. The transition temperature of a superconductor is known as the critical temperature, \(T_c\), and is a material-specific property.