Move your body

Researchers in Belgium have developed an easy-to-use and make magnetic transporting device that paves the way for new biosensor applications. Els Parton, Roel Wirix-Speetjens and Gustaaf Borghs of IMEC report.

Magnetic-bead-based biosensors are a promising tool for the detection of DNA, proteins and cells. Thanks to their integrated magneto-resistive sensors, they offer a high sensitivity and low detection limit.

The ability to use a magnetic force to move the magnetic beads - with attached biomolecules - over the chip surface opens up new possibilities for lab-on-chip diagnostic applications.

Researchers in Belgium have now developed a magnetic transporting device that beats its predecessors in its simplicity in use and fabrication. It consists of only two current-carrying wires, built up out of shark-fin-like structural elements.

No external magnetic field is required to guide the particles along a predefined path of local magnetic-field maxima.

The Human Genome Project has opened up new perspectives for medicine. In the future, detection of specific DNA sequences and proteins will be increasingly important in diagnosing and curing diseases.

Nowadays, fluorescent labelling is often used to detect specific target molecules. With the advent of the biosensor, a relatively cheap, small, fast and easy-to-use alternative was born, enabling a broad range of new applications (eg point-of-care diagnostics).

Biosensors measure differences in current, voltage, temperature or frequency to detect binding of target molecules with receptors.

In 1998, the US Naval Research Laboratory researchers launched the idea of using magneto-resistive sensors and magnetic beads for biosensor applications. Although the magnetic-bead labelling of the biomolecules requires an extra step in the procedure, magnetic biosensors offer huge advantages over label-free biosensors.


The five plusses of magnetic biosensors
Like most biosensors, magnetic biosensors make use of receptor molecules, immobilised on the chip surface, to recognise and bind the 'target' molecules.

Once the target molecules in the test solution (eg blood) have bound to these receptors, magnetic nanoparticles are added. A special coating with a biochemical surface function enables the magnetic particles to bind to the immobilised target molecules.

After removal of nonhybridised material, the magnetic labels are detected with ultra-sensitive giant magneto-resistive sensor devices, integrated on the chip surface. This last aspect, the use of ultra-sensitive magneto-resistive sensors, brings us to the first advantage of magnetic biosensors: a high sensitivity and low detection limit.

The second plus is that a magnetic force can be applied to the magnetic particles to guide them, for example, to the spin-valve sensor, and thus increase the sensitivity of the biosensor.

Another use of on-chip magnetic transport of the particles is in so-called lab-on-chip applications in which the magnetic beads are subsequently used for sample pre-treatment, transport to the chip-bound receptor molecules and transport to the detection area.

The transport of magnetic labels in a magnetic bead-based biosensor can be creatively used to further enhance the biosensor's capabilities. For example, a magnetic force applied perpendicular to the chip surface can bring the biomolecules closer to the surface and in this way increase the speed and efficiency of the recognition event.

A perpendicular magnetic force in the opposite direction (pointing away from the chip surface) can be used to remove non-specific bound biomolecules, thus increasing the selectivity of the biosensor.


New and simple method for on-chip magnetic-bead transport
Several research groups have demonstrated on-chip magnetic-bead transport, mostly based on rather complex designs such as two-dimensional arrays of conducting wires in multiple layers [1] or magnetic tracks, which make use of an external magnetic field [2].

The new device developed by the Belgium researchers, based on shark-fin-like structural elements (top view), was made using standard semiconductor fabrication and photolithography techniques.

Only one metallization step was needed to place the current conductors - consisting of TiW 10nm/Au 150 nm/TiW 10nm - onto the silicon substrate with 300nm thermal SiO2.

TiW and Au were evaporated and patterned using a lift-off process. Polyimide was used as a passivation layer, with openings as contact paths to the conductors. Finally, the device was packaged so the magnetic-particle fluid could to be dispensed onto the chip's surface.

The new magnetic-bead transporting device consists of two tapered conductors, placed next to each other. When putting a dc current through the upper conductor, a low current density - and thus small magnetic field - is present in the large cross-section of the shark-fin structural element of the conducting wire.

Meanwhile, a high current density - and thus large magnetic field - is present at the smallest cross-section of the shark-fin. In this way, a magnetic-field gradient is created along each structural element, attracting magnetic beads towards the right-most tip of the structure.

Next, a current pulse is sent to the lower conductor, whose structural elements are shifted slightly to the right compared to the upper conductor. A magnetic-field maximum is now created at the narrow right-most tip of the structural element and the magnetic beads jump from the upper conductor to the lower conductor.

In this way, a one-dimensional stepwise transport is realised when low-frequency non-overlapping clock pulses are put through both conductors alternatively.

Experiments were set up using uniform magnetic particles 2µm in size. They contain 15% magnetite (Fe3O4) in a polymer matrix and can easily be coated with covalently bound DNA and proteins. The magnetic particles were suspended in water (0.0625mg/ml). Some 3µl of the solution was applied to the chip surface.

Different sizes of the basic repetitive conductor element were tested: widths of 20µm, 30µm and 40µm and lengths of 10µm, 40µm, 60µm and 100µm (the smallest cross section was always 6µm). A current of 50mA was applied alternately through the two conductors at a frequency of 0.10Hz.

Researchers examined how they could influence the average speed of the magnetic particles. The average speed can be deduced from the maximum frequency at which the currents can be switched without disturbing the transport.

They concluded that the speed of the magnetic beads can be increased in three different ways:

1. Increasing the current in the conductors will increase the magnetic-field gradient, and thus the speed of the beads;

2. Decreasing the length of the shark-fin structures will increase the magnetic-field gradient, and thus also the speed of the bead transport (however, there is a threshold length at which the average speed no longer increases but becomes zero);

3. Decreasing the width of the basic structural elements will reduce the magnetic-field gradient, but it will also increase the average current density. The effect of the latter is dominant, so the average speed of the magnetic particles will increase.


Conclusion
Researchers have developed a device to guide magnetic particles along a defined track based on a set of two tapered current conductors. The fabrication of the device is based on standard semiconductor fabrication and photolithography techniques and requires only one metallization step.

The speed of the magnetic-particle transport can be increased by boosting the current intensity, reducing the length or decreasing the width of the repetitive triangular structure the conductor is made of.

This new and simple transport system opens up new opportunities for manipulation of magnetic labelled biomolecules within lab-on-chip devices.



References:

[1] Microelectromagnets for the control of magnetic nanoparticles, C Lee et al, Appl Phys Lett 79: 3308-3310 (2001).

[2] Manipulation of magnetic microbeads in suspension using micromagnetic systems fabricated with soft lithography, T Deng et al, Appl Phys Lett 78: 1775-1777 (2001).

Figure 1: Working principle of a magnetic-bead-based biosensor.

Figure 2: Magnetic particles move along a defined track of magnetic-field maxima.

Figure 2b: The packaged magnetic-bead-transport device.

Figure 3: Microscopic images of stepwise movement of magnetic particles along the new transport device.

Figure 4

Figure 5: Influence of scaling the width of the basic structural element on the average speed of a magnetic particle.

Figure 6: Influence of scaling the length of the basic structural element on the average speed of a magnetic particle.