Sensitive Readout for Microfluidic High-Throughput Applications using Scanning SQUID Microscopy

Abstract

Microfluidic chips provide a powerful platform for high-throughput screening of diverse biophysical systems. The most prevalent detection methods are fluorescence based. Developing new readout techniques for microfluidics focusing on quantitative information in the low signal regime is desirable. In this work, we combine the well-established immunoassay approach, with magnetic nanoparticles, with a highly sensitive magnetic imaging technique. We offer to integrate a microfluidic array into a scanning superconducting quantum interference device (SQUID) microscope, to image nanoparticles that were moved through the microfluidic device. We demonstrate the technique on protein-protein interactions (PPI). We compare sensitivity to that of a conventional readout, quantify the amount of interactions, and demonstrate 0.1 atto-mole sensitivity. Our work serves as a proof of concept that will promote the development of a new set of eyes, a stable usable microfluidic-scanning SQUID microscopy.

Quantum‐Based Magnetic Field Sensors for Biosensing

“…Also, SQUIDs are usually combined with the technology of microfluidics to achieve all steps of an assay on a disposable lab-on-a-chip and highthroughput screening. [12,82] In addition to antibody detection in immunoassays, SQUID-based readouts of protein-protein interactions, [11] DNA and RNA targets [82] were published. One of the recent examples of integrating a microfluidic array into a scanning SQUID microscope to image nanoparticle distribution through the microfluidic devices was presented by Wissberg et al (Figure 2B).…”

“…[5,6] Compared to the Earth's magnetic field (48 μT in Central Europe), these weak biomagnetic signals in the fT range [7] are difficult to measure accurately. Magnetic nanoparticles (MNPs), which have affinities for conjugating ligands for pathogenic bacteria, [8] tumor markers, [9,10] proteins, [11,12] nucleic acids, [13] and other biomolecules, [14,15] can be used as magnetic labels in point-of-care testing. It is also crucial to improve the limit of detection (LOD) to realize early disease diagnosis.…”

An electrochemical method for measuring magnetic flux density

“…SQUID has been widely used in scanning SQUID microscopy, medical diagnostics and quantum computing. 26–28…”

“…SQUID has been widely used in scanning SQUID microscopy, medical diagnostics and quantum computing. [26][27][28] These methods for measurement of magnetic ux density require Gauss meter, thus it is more complex for measuring the MFD than potential. If there is method to measure the MFD by potentiometer, it will make the measurement for MFD more convenient and can be applied to more elds.…”

Experimental study on the characteristics of near‐field distribution of chips based on nano‐diamond quantum magnetometer

“…However, the spatial resolution decreases with the increase of sensitivity. Compared to traditional test probes, such as open waveguides, superconducting quantum interference device (SQUID), metallic open-ended waveguides (OEWs), tunnel magnetoresistance effect (TMR) sensor, and giant magnetoresistance effect sensor, [7][8][9] especially in the measurement of the antenna system, the metallic nature of the probes may cause interference to the measured field, and the resolution is low due to the large probe size (the resolution is usually about 100 μm). These shortcomings restrict the application range of the above technology.…”