Tsukasa Takamura

Magnetic-Particle-Sensing Based Diagnostic Protocols and Applications

Magnetic particle-labeled biomaterial detection has attracted much attention in recent years for a number of reasons; easy manipulation by external magnetic fields, easy functionalization of the surface, and large surface-to-volume ratio, to name but a few. In this review, we report on our recent investigations into the detection of nano-sized magnetic particles. First, the detection by Hall magnetic sensor with lock-in amplifier and alternative magnetic field is summarized. Then, our approach to detect sub-200 nm diameter target magnetic particles via relatively large micoro-sized “columnar particles” by optical microscopy is described. Subsequently, we summarize magnetic particle detection based on optical techniques; one method is based on the scattering of the magnetically-assembled nano-sized magnetic bead chain in rotating magnetic fields and the other one is based on the reflection of magnetic target particles and porous silicon. Finally, we report recent works with reference to more familiar industrial products (such as smartphone-based medical diagnosis systems and magnetic removal of unspecific-binded nano-sized particles, or “magnetic washing”).

Amplification of direct current magnetic responses of magnetic nanobeads due to induced self-assembly of magnetic microbeads

Detection of small concentrations of sub-200-nm-sized SPBs (superparamagnetic beads with sizes similar to target molecules) used as ‘magnetic labels’ is critical for the development of rapid, highly sensitive, and portable point of care treatment (POCT) systems. Currently, magnetoresistive (MR) biosensors are used for the detection of large concentrations of SPBs but such an approach is not suitable for monitoring small numbers of sub-200-nm SPBs due to the intrinsic noise of these electronic devices. In order to overcome this limitation of conventional MR sensors, we have developed a simple procedure for detecting small concentrations of sub-200-nm-diameter SPBs for biosensing by exploiting magnetically induced self-assembly of micrometer-sized SPBs onto nanometer targets. Here, our approach enables the physical amplification of the signal from otherwise undetectable nano-SPB targets using Hall biosensors without using the application of ac, magnetic fields or lock-in detection, thereby enabling the prod...

Compact electromagnetically operated microfluidic system for detection of sub-200-nm magnetic labels for biosensing without external pumps

The combination of small sample analyte volumes, high sensitivity, ease of use, high speed, and portability is an important factor for the development of protocols for point of care biodiagnosis. Currently, handling small amounts of liquids is achieved using microfluidic systems but it is challenging to satisfy the remaining factors using conventional approaches based on biosensors employing detection of fluorescent labels. Thus to resolve the other requirements, biosensing systems based on the detection of functionalized superparamagnetic beads acting as “magnetic labels” are being studied as an alternative approach. Notably, for greater quantification, there are increasing demands for the use of sub-200-nm magnetic labels, which are comparable in size to actual biomolecules. However, detection of small numbers of sub-200-nm diameter magnetic beads by magnetoresistive device-based platforms is extremely challenging due to the intrinsic noise of the electronic devices. In order to overcome the limitation,...

Wide wavelength range tunable one-dimensional silicon nitride nano-grating guided mode resonance filter based on azimuthal rotation

We describe wavelength tuning in a one dimensional (1D) silicon nitride nano-grating guided mode resonance (GMR) structure under conical mounting configuration of the device. When the GMR structure is rotated about the axis perpendicular to the surface of the device (azimuthal rotation) for light incident at oblique angles, the conditions for resonance are different than for conventional GMR structures under classical mounting. These resonance conditions enable tuning of the GMR peak position over a wide range of wavelengths. We experimental demonstrate tuning over a range of 375 nm between 500 nm˜875 nm. We present a theoretical model to explain the resonance conditions observed in our experiments and predict the peak positions with show excellent agreement with experiments. Our method for tuning wavelengths is simpler and more efficient than conventional procedures that employ variations in the design parameters of structures or conical mounting of two-dimensional (2D) GMR structures and enables a singl...

Planar Microfluidic System Based on Electrophoresis for Detection of 130-nm Magnetic Labels for Biosensing

Superparamagnetic beads (SPBs) used as magnetic labels offer potential for the realization of high sensitivity and low cost biosensors for point of care treatment (POCT). For better biomolecular affinity and higher sensitivity, it is desirable to use sub-200-nm-diameter SPBs comparable in size to actual biomolecules. However, the detection of small concentrations of such SPBs by magnetoresistive devices is extremely challenging due to small magnetic response of SPBs. As a solution to these limitations, we describe a simple detecting procedure where the capture of micro-SPBs by immobilized nano-target SPBs due to self-assembly induced by an external magnetic field, which was monitored under an optical microscope. Here we describe biosensing system based on self-assembly of micro-SPBs by nanoSPBs targets using a system without external pumps, thereby enabling greater miniaturization and portability.

Porous Silicon Based Protocol for the Rapid and Real-Time Monitoring of Biorecognition Between Human IgG and Protein A Using Functionalized Superparamagnetic Beads

Optical interferometer biosensors based on porous silicon (PSi) are being studied for chemical and biological sensor applications. In particular, single PSi is a promising sensing platform for biomolecules and based on monitoring changes in the optical thickness (2nL) from Fabry-Pérot fringes due to magnetic particle-labels covering PSi surfaces. These methods offer a fast, and one-step method for immunoassaying by combining nano-sized superparamagnetic beads (SPBs) with interferometer PSi platforms. Furthermore, SPBs covered with biomolecules have a higher reflective index than the biomolecules alone, which results in larger shifts of the optical thickness (2nL) by the penetration of SPBs inside pore walls of PSi. In this work, we immobilized protein A onto macropore PSi and used optical reflection to detect human IgG immobilized onto nano-sized SPBs by measuring changes of optical thickness (2nL). Furthermore, the optical thickness (2nL) was proportional to mass of the biomolecules, thus the Δ2nL corresponded to the mass fraction of active IgG with SPBs inside PSi pores. Therefore, we quantified the changes of optical thickness (2nL) to enable the detection of SPBs functionalized human IgG based on protein-A modified macropore sized PSi platform.

Optical Transmittance for Analysis of the Dynamics of Self-Assembled Rotating Chains of Superparamagnetic Micro- and Nano Beads in Solution

Optically monitoring biosensing procedures based on the dynamics of an aqueous solution containing functionalized superparamagnetic beads in the application of the external rotating magnetic field has been developed for a rapid, highly sensitive, and inexpensive bioassay. Typically, the dynamics of micrometer diameter beads is observed by conventional optical microscopes. For greater affinity to biomolecules, there is a demand which necessitates the use of nanometer sized superparamagnetic beads, comparable size to actual biomolecules. However, a limited amount of work for monitoring the dynamics of nanometer sized beads has been performed thus far due to the maximum resolution of microscopes. Here, we propose a novel protocol enabling us monitor the dynamics of nanometer-diameter beads via change in the optical transmittance.

Detection of Nanometer Magnetic Labels' Concentration Via the Movement of Micrometer Superparamagnetic in Application of Magnetic Field

Research on medical diagnostics for point of care treatment (POCT) is driven by demand for rapid, high sensitivity, and inexpensive point of care diagnosis of heart disease, infection, allergies and cancer. Demands to improve quantification and affinity necessitate magnetic labels with sizes comparable to target molecules. However, it is extremely challenging to detect small concentrations of sub-200 nm functionalized magnetic labels using magnetoresistive-based sensors. In order to overcome these limitations we have developed a simple procedure for detecting ~ 130 nm sized magnetic labels via magnetically induced capture of micrometer sized superparamagnetic beads by several 130 nm-diameter target beads immobilized on substrates. Here we demonstrate a new method to improve the quantification of our protocol that exploits magnetically induced frictional forces between micro-sized beads and target magnetic labels. By reducing the external magnetic field, the magnetically captured micro-sized beads restart to flow due to electrostatic forces and the strength of the critical external magnetic field for release depends on the number of nano-sized beads immobilized on substrate. Our protocol has the possibility for quantitative biomaterial detection.

Point of care biosensing protocol based on magnetically induced self-assembly of functionalized particles dispersed in colloids

1 Department of Electrical and Electronic Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan 2 Advanced Materials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084, People’s Republic of China 3 Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku, Toyohashi 441-8580, Japan

Compact Electro-Magnetically Operated Microfluidic System for Detection of sub-200 nm Magnetic Labels for Biosensing without External Pumps

1 Department of Electrical and Electronic Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan Telephone/facsimile. +81-3-5734-2807, E-mail : takamura.t.ab@m.titech.ac.jp 2 Tokyo Tech Global COE Program on Evolving Education and Research Center For Spatio-Temporal Biological Network, Tokyo, 152-8552, Japan 3 Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan