Ioanna Giouroudi

Microfluidic Biosensing Systems Using Magnetic Nanoparticles

In recent years, there has been rapidly growing interest in developing hand held, sensitive and cost-effective on-chip biosensing systems that directly translate the presence of certain bioanalytes (e.g., biomolecules, cells and viruses) into an electronic signal. The impressive and rapid progress in micro- and nanotechnology as well as in biotechnology enables the integration of a variety of analytical functions in a single chip. All necessary sample handling and analysis steps are then performed within the chip. Microfluidic systems for biomedical analysis usually consist of a set of units, which guarantees the manipulation, detection and recognition of bioanalytes in a reliable and flexible manner. Additionally, the use of magnetic fields for performing the aforementioned tasks has been steadily gaining interest. This is because magnetic fields can be well tuned and applied either externally or from a directly integrated solution in the biosensing system. In combination with these applied magnetic fields, magnetic nanoparticles are utilized. Some of the merits of magnetic nanoparticles are the possibility of manipulating them inside microfluidic channels by utilizing high gradient magnetic fields, their detection by integrated magnetic microsensors, and their flexibility due to functionalization by means of surface modification and specific binding. Their multi-functionality is what makes them ideal candidates as the active component in miniaturized on-chip biosensing systems. In this review, focus will be given to the type of biosening systems that use microfluidics in combination with magnetoresistive sensors and detect the presence of bioanalyte tagged with magnetic nanoparticles.

Recent Progress in Biomedical Applications of Magnetic Nanoparticles

Magnetic nanoparticles have been proposed for biomedical applications for several years. Various research groups worldwide have focused on improving their synthesis, their characterization techniques and the specific tailoring of their properties. Yet, it is the recent, impressive advances in nanotechnology and biotechnology which caused the breakthrough in their successful application in biomedicine. This paper aims at reviewing some current biomedical applications of magnetic nanoparticles as well as some recent patents in this field. Special emphasis is placed on i) hyperthermia, ii) therapeutics iii) diagnostics. Future prospects are also discussed.

A giant magnetoresistance ring-sensor based microsystem for magnetic bead manipulation and detection

In this paper a novel spin valve giant magnetoresistance (GMR) ring-sensor integrated with a microstructure is proposed for concentrating, trapping, and detecting superparamagnetic beads (SPBs). Taking advantage of the fact that SPBs can be manipulated by an external magnetic field, a unique arrangement of conducting microrings is utilized to manipulate the SPBs toward the GMR sensing area in order to increase the reliability of detection. The microrings are arranged and activated in such a manner so as to enable the detection of minute concentrations of SPBs in a sample. Precise manipulation is achieved by applying current sequentially to the microrings. The fabricated ring-shaped GMR element is located underneath the innermost ring and has a magnetoresistance of approximately 5.9%. By the performed experiments it was shown that SPBs could be successfully manipulated toward the GMR sensing zone.

An integrated micro-chip for rapid detection of magnetic particles

This paper proposes an integrated micro-chip for the manipulation and detection of magnetic particles (MPs). A conducting ring structure is used to manipulate MPs toward giant magnetoresistance (GMR) sensing elements for rapid detection. The GMR sensor is fabricated in a horseshoe shape in order to detect the majority of MPs that are trapped around the conducting structure. The GMR sensing elements are connected in a Wheatstone bridge circuit topology for optimum noise suppression. Full fabrication details of the micro-chip, characterization of the GMR sensors, and experimental results with MPs are presented in this paper. Experimental results showed that the micro-chip can detect MPs from low concentration samples after they were guided toward the GMR sensors by applying current to the conducting ring structure.

On-chip microfluidic biosensor using superparamagnetic microparticles

In this paper, an integrated solution towards an on-chip microfluidic biosensor using the magnetically induced motion of functionalized superparamagnetic microparticles (SMPs) is presented. The concept of the proposed method is that the induced velocity on SMPs in suspension, while imposed to a magnetic field gradient, is inversely proportional to their volume. Specifically, a velocity variation of suspended functionalized SMPs inside a detection microchannel with respect to a reference velocity, specified in a parallel reference microchannel, indicates an increase in their non-magnetic volume. This volumetric increase of the SMPs is caused by the binding of organic compounds (e.g., biomolecules) to their functionalized surface. The new compounds with the increased non-magnetic volume are called loaded SMPs (LSMPs). The magnetic force required for the manipulation of the SMPs and LSMPs is produced by current currying conducting microstructures, driven by a programmable microcontroller. Experiments were carried out as a proof of concept. A promising decrease in the velocity of the LSMPs in comparison to that of the SMPs was measured. Thus, it is the velocity variation which determines the presence of the organic compounds in the sample fluid.

Magnetic-based biomolecule detection using giant magnetoresistance sensors

This paper presents a novel microfluidic chip for in-vitro detection of biomolecules tagged by magnetic microparticles (MAPs) suspended in a static fluid. The system consists of two microfluidic channels: a reference channel in which bare MAPs are suspended and a detection channel in which magnetically tagged biomolecules are suspended (LMAPs). The LMAPs are functionalized MAPs (of the same magnetic volume as the ones in the reference channel) with attached biomolecules. The overall, non-magnetic volume of the LMAPs is greater than that of the bare MAPs. Current carrying microconductors are positioned underneath the channels in order to impose a magnetic field gradient to the MAPs and LMAPs and move them from the inlet to the outlet of the channels without flow. The innovative aspect of the proposed method is that the induced velocity on the MAPs and LMAPs, while imposed to the same magnetic field gradient, is inversely proportional to their overall, non-magnetic volume. This is due to the enhanced Stokes...

Anatomical Study of the Radius and Center of Curvature of the Distal Femoral Condyle

In this anatomical study, the anteroposterior curvature of the surface of 16 cadaveric distal femurs was examined in terms of radii and center point. Those two parameters attract high interest due to their significance for total knee arthroplasty. Basically, two different conclusions have been drawn in foregoing studies: (1) The curvature shows a constant radius and (2) the curvature shows a variable radius. The investigations were based on a new method combining three-dimensional laser-scanning and planar geometrical analyses. This method is aimed at providing high accuracy and high local resolution. The high-precision laser scanning enables the exact reproduction of the distal femurs-including their cartilage tissue-as a three-dimensional computer model. The surface curvature was investigated on intersection planes that were oriented perpendicularly to the surgical epicondylar line. Three planes were placed at the central part of each condyle. The intersection of either plane with the femur model was approximated with the help of a b-spline, yielding three b-splines on each condyle. The radii and center points of the circles, approximating the local curvature of the b-splines, were then evaluated. The results from all three b-splines were averaged in order to increase the reliability of the method. The results show the variation in the surface curvatures of the investigated samples of condyles. These variations are expressed in the pattern of the center points and the radii of the curvatures. The standard deviations of the radii for a 90 deg arc on the posterior condyle range from 0.6 mm up to 5.1 mm, with an average of 2.4 mm laterally and 2.2 mm medially. No correlation was found between the curvature of the lateral and medial condyles. Within the range of the investigated 16 samples, the conclusion can be drawn that the condyle surface curvature is not constant and different for all specimens when viewed along the surgical epicondylar axis. For the portion of the condylar surface that articulates with the tibia during knee flexion-extension, the determined center points approximate the location of the centers of rotation. The results suggest that the concept of a fixed flexion-extension axis is not applicable for every specimen.

Microfluidics for the Rapid Detection of Pathogens Using Giant Magnetoresistance Sensors

This paper presents an integrated solution toward an on-chip microfluidic diagnostic system using the magnetically induced motion of functionalized magnetic microparticles (MPs) in combination with giant magnetoresistance (GMR) sensors. The innovative aspect of the proposed method is that the induced velocity on MPs in suspension, while imposed to a magnetic field gradient, is inversely proportional to their volume. Specifically, a velocity variation of suspended functionalized MPs inside a detection microchannel with respect to a reference velocity, specified in a parallel reference microchannel, indicates an increase in their nonmagnetic volume. This volumetric increase of the MPs is caused by the binding of pathogens (e.g., bacteria) to their functionalized surface. The new formed compounds, which have an increased nonmagnetic volume, are called loaded MPs (LMPs). Experiments with functionalized MPs and LMPs with Escherichia coli attached to their surface were conducted as a proof of concept. Their movement was demonstrated optically by means of a microscope with a mounted CCD camera as well as by measuring the resistance change of the integrated GMR sensors.

A biodetection method using magnetic particles and micro traps

The general working principle of magnetoresistive sensors for biological applications is to specifically attach bioanalytesto magnetic particles and then detect the particles that are immobilized on the sensor surface. The immobilization of the particles on the sensor surface commonly uses biomolecular interactions, e.g., antigen-antibody. Thus, the sensor surface needs to be functionalized via biological treatments in order to capture certain bioanalytes. In the presented work, a new method is proposed, which does not rely on functionalization of the sensor surface. Current carrying microstructures in combination with mechanical micro traps are used to immobilize magnetic particles. Analyte detection is based on the difference in size between bare magnetic particles and particles with analyte attached, which causes a different number of particles to be captured in the micro traps.

Selective Manipulation of Superparamagnetic Beads by a Magnetic Microchip

In this paper, a magnetic microchip (MMC) is presented, to first trap and then selectively manipulate individual, superparamagnetic beads (SPBs) to another trapping site. Trapping sites are realized through soft magnetic micro disks made of Ni80Fe20, and SPB motion is controlled by current-carrying, tapered, conducting lines made of Au. The MMC was realized using standard microfabrication techniques and provides a cheap and versatile platform for microfluidic systems for cell manipulation.