Georgios Kokkinis

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...

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 novel approach for detection and quantification of magnetic nanomarkers using a spin valve GMR-integrated microfluidic sensor

We demonstrate the application of a spin valve giant magneto-resistance (GMR) integrated microfluidic sensor for the detection and quantification of superparamagnetic nanomarkers. A microfluidic channel containing the magnetic fluid, micro-conductors (MCs) for collection of magnetic markers and a spin valve GMR sensor for detecting the presence of magnetic stray field were integrated into a single chip and employed for detection of various concentrations of Nanomag-D beads of 250 nm diameter. The results show that the sensor is capable of detecting concentrations as low as 500 pg μl−1 of Nanomag-D beads and quantifying them in a linear scale over a wide particle concentration range (1–500 ng μl−1). Our study provides a novel platform towards the development of a portable lab-on-a-chip sensor.

Recent Advances in Magnetic Microfluidic Biosensors

The development of portable biosening devices for the detection of biological entities such as biomolecules, pathogens, and cells has become extremely significant over the past years. Scientific research, driven by the promise for miniaturization and integration of complex laboratory equipment on inexpensive, reliable, and accurate devices, has successfully shifted several analytical and diagnostic methods to the submillimeter scale. The miniaturization process was made possible with the birth of microfluidics, a technology that could confine, manipulate, and mix very small volumes of liquids on devices integrated on standard silicon technology chips. Such devices are then directly translating the presence of these entities into an electronic signal that can be read out with a portable instrumentation. For the aforementioned tasks, the use of magnetic markers (magnetic particles—MPs—functionalized with ligands) in combination with the application of magnetic fields is being strongly investigated by research groups worldwide. The greatest merits of using magnetic fields are that they can be applied either externally or from integrated microconductors and they can be well-tuned by adjusting the applied current on the microconductors. Moreover, the magnetic markers can be manipulated inside microfluidic channels by high gradient magnetic fields that can in turn be detected by magnetic sensors. All the above make this technology an ideal candidate for the development of such microfluidic biosensors. In this review, focus is given only to very recent advances in biosensors that use microfluidics in combination with magnetic sensors and magnetic markers/nanoparticles.

Magnetic Microfluidic Platform for Biomedical Applications Using Magnetic Nanoparticles

Microfluidic platforms are well-suited for biomedical analysis and usually consist of a set of units which guarantee the manipulation, detection and recognition of bioanalyte in a reliable and flexible manner. Additionally, the use of magnetic fields for perfoming the aforementioned tasks has been steadily gainining interest. This is due to the fact that magnetic fields can be well tuned and applied either externally or from a directly integrated solution in the diagnostic system. In combination with these applied magnetic fields, magnetic nanoparticles are used. In this paper, we present some of our most recent results in research towards a) microfluidic diagnostics using MR sensors and magnetic particles and b) single cell analysis using magnetic particles. We have successfully manipulated magnetically labeled bacteria and measured their response with integrated GMR sensors and we have also managed to separate magnetically labeled jurkat cells for single cell analysis.

Microfluidic Biosensing Method Using the Motion of Magnetic Microparticles

In this paper a microfluidic biosensing method for detecting a bioanalyte using the motion of magnetic microparticles (MPs) is presented. The system consists of a microfluidic channel, in which the MPs are suspended and current carrying microconductors positioned underneath the channel. These microconductors are used in order to move the MPs from the inlet to the outlet of the channel. The MPs are functionalized by modifying their surface, thus enabling them to chemically bind to a specific (non-magnetic) bioanalyte. Once the MPs binds to the bioanalyte new compounds are formed (LMPs). These compounds have a bigger overall volume than the bare MPs but still the same magnetic volume. The MPs and LMPs are manipulated inside the microfluidic channel by exposing them to magnetic field generated by the microconductors. When both, MPs and LMPs, are accelerated by the same magnetic field density, the LMPs are going to be slower than the MPs due to their increased (non-magnetic) volume. This difference in velocity is used to discriminate between MPs and LMPs. Calculations concerning the velocity change of MPs and the magnetic field generated by the current carrying microconductors were carried out. Simulations of various geometries for the conductors and various MPs were performed using finite element analysis software. Several chips were fabricated and experiments with different MPs and LMPs were conducted as a proof of concept.

Microfluidic Biosensing Device for Controlled Trapping and Detection of Magnetic Microparticles

A magnetic microfluidic device is proposed to transport and trap magnetic microparticles (MPs) to a sensing area. Once the MPs are concentrated in the vicinity of the sensing area, a spin valve type giant magnetoresistance (GMR) sensor is used to detect their presence. The device is used for the detection of biological targets once they are labeled with functionalized MPs. Manipulation of the MPs is achieved by employing a microstructure which consists of planar ring-shaped conducting microloops. These microloops are designed to produce high magnetic field gradients which are directly proportional to the force applied to manipulate the MPs. Upon sequential application of current, starting from the outermost loop, MPs are directed to move from the outermost to the innermost loop. The speed with which the MPs move towards the sensing area is controlled by the speed with which current is switched between the loops. On top of the microstructure, a microfluidic channel is fabricated using a standard photolithography technique and a dry film resist layer (Ordyl SY355). Experimental results showed that MPs of different diameters were successfully trapped at the sensing area and detected by the GMR sensor located directly under the innermost square loop.

Biosensing System for Concentration Quantification of Magnetically Labeled E. coli in Water Samples

Bacterial contamination of water sources (e.g., lakes, rivers and springs) from waterborne bacteria is a crucial water safety issue and its prevention is of the utmost significance since it threatens the health and well-being of wildlife, livestock, and human populations and can lead to serious illness and even death. Rapid and multiplexed measurement of such waterborne pathogens is vital and the challenge is to instantly detect in these liquid samples different types of pathogens with high sensitivity and specificity. In this work, we propose a biosensing system in which the bacteria are labelled with streptavidin coated magnetic markers (MPs—magnetic particles) forming compounds (MLBs—magnetically labelled bacteria). Video microscopy in combination with a particle tracking software are used for their detection and quantification. When the liquid containing the MLBs is introduced into the developed, microfluidic platform, the MLBs are accelerated towards the outlet by means of a magnetic field gradient generated by integrated microconductors, which are sequentially switched ON and OFF by a microcontroller. The velocities of the MLBs and that of reference MPs, suspended in the same liquid in a parallel reference microfluidic channel, are calculated and compared in real time by a digital camera mounted on a conventional optical microscope in combination with a particle trajectory tracking software. The MLBs will be slower than the reference MPs due to the enhanced Stokes’ drag force exerted on them, resulting from their greater volume and altered hydrodynamic shape. The results of the investigation showed that the parameters obtained from this method emerged as reliable predictors for E. coli concentrations.

Microfluidic platform for detection and quantification of magnetic markers

This paper reports on a microfluidic platform with an integrated spin valve giant magneto-resistance (GMR) sensor used for the detection and quantification of single magnetic micromarkers. A microfluidic channel containing the magnetic fluid, microconductors (MCs) for collection of the magnetic markers and a spin valve GMR sensor for detecting the presence of their magnetic stray field were integrated on a single chip. The results show that the sensor is capable of detecting a single magnetic marker with 2.8 μm diameter.