Justin F. Schneiderman

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.

Information content with low- vs. high-Tc SQUID arrays in MEG recordings: The case for high-Tc SQUID-based MEG

BACKGROUND Magnetoencephalography (MEG) is a method of studying brain activity via recordings of the magnetic field generated by neural activity. Modern MEG systems employ an array of low critical-temperature superconducting quantum interference devices (low-Tc SQUIDs) that surround the head. The geometric distribution of these arrays is optimized by maximizing the information content available to the system in brain activity recordings according to Shannons theory of noisy channel capacity. NEW METHOD Herein, we present a theoretical comparison of the performance of low- and high-Tc SQUID-based multichannel systems in recordings of brain activity. RESULTS We find a high-Tc SQUID magnetometer-based multichannel system is capable of extracting at least 40% more information than an equivalent low-Tc SQUID system. The results suggest more information can be extracted from high-Tc SQUID MEG recordings (despite higher sensor noise levels than their low-Tc counterparts) because of the closer proximity to neural sources in the brain. COMPARISON WITH EXISTING METHODS We have duplicated previous results in terms of total information of multichannel low-Tc SQUID arrays for MEG. High-Tc SQUID technology theoretically outperforms its conventional low-Tc counterpart in MEG recordings. CONCLUSIONS A full-head high-Tc SQUID-based MEG systems potential for extraction of more information about neural activity can be used to, e.g., develop better diagnostic and monitoring techniques for brain disease and enhance our understanding of the working human brain.

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.

Free evolution of superposition states in a single Cooper pair box

We have fabricated a single Cooper-pair box (SCB) in close proximity to a single electron transistor (SET) operated in the radio-frequency mode (RF-SET) with an inductor and capacitor lithographed directly on chip. The RF-SET was used to measure the charge state of the SCB revealing a 2e periodic charge quantization. We performed spectroscopy measurements to extract the charging energy (E C ) and the Josephson coupling energy (E J ). Control of the temporal evolution of the quantum charge state was achieved by applying fast dc pulses to the SCB gate. The dephasing and relaxation times were extracted from these measurements.

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.

Experimental Realization of a Differential Charge Qubit

We demonstrate the operation of a differential single Cooper-pair box, a charge qubit consisting of two aluminum islands, isolated from ground, coupled by a pair of small-area Josephson junctions. We have tested four devices, all of which show evidence of quasiparticle poisoning. The devices are characterized with microwave spectroscopy and temperature dependence studies.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.

Quasiparticle Poisoning in a Single Cooper-Pair Box

We investigate the pheonomenon of quasiparticle poisoning in a single Cooper‐pair box (SCB). We have designed, fabricated, and tested an SCB that demonstrates a transition between poisoned and unpoisoned Coulomb staircases, depending on the speed with which the gate charge is swept. Poisoning is shown to be suppressed at moderately high sweep rates. Coulomb staircases were measured for a variety of sweep rates, and quasiparticle tunneling rates were extracted from this data.