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A planar conducting microstructure to guide and confine magnetic beads to a sensing zone
Microelectronic Engineering 88 (2011) 1757–1760
Contents lists available at ScienceDirect
Microelectronic Engineering journal homepage: www.elsevier.com/locate/mee
A planar conducting microstructure to guide and confine magnetic beads to a sensing zone Chinthaka P. Gooneratne ⇑, Cai Liang, Jürgen Kosel Division of Physical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
a r t i c l e
i n f o
Article history: Available online 25 December 2010 Keywords: Magnetic beads Microstructure Microfluidics GMR sensor
a b s t r a c t A novel planar conducting microstructure is proposed to transport and confine magnetic micro/nano beads to a sensing zone. Manipulation and concentration of magnetic beads are achieved by employing square-shaped conducting micro-loops, with a few hundred nano-meters in thickness, arranged in a unique fashion. These microstructures are designed to produce high magnetic field gradients which are directly proportional to the force applied to manipulate the magnetic beads. Furthermore, the size of the microstructures allows greater maneuverability and control of magnetic beads than what could be achieved by permanent magnets. The aim of the microstructures is to guide magnetic beads from a large area and confine them to a smaller area where for example quantification would take place. Experiments were performed with different concentrations of 2 lm diameter magnetic beads. Experimental results showed that magnetic beads could be successfully guided and confined to the sensing zone. Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction The past decade has seen an unprecedented increase in interest for utilizing magnetic beads in microfluidic devices [1]. Magnetic beads can be seamlessly integrated into systems on a chip due to, their micro/nano size, large specific surface areas available for binding biomolecules, being independent of reagent chemistry or photo-bleaching as well as being biocompatible with no toxicity index [2,3]. Superparamagnetic-type magnetic beads have attracted a lot of attention in recent times [4]. They do not have a magnetic moment in the absence of an external magnetic field but become magnetized once an external magnetic field is applied. Hence, unlike ferromagnetic materials, they do not exhibit a remanent magnetization. This not only prevents the agglomeration of magnetic beads but also enables an external magnetic field to control the beads remotely. Hence, magnetic beads are for example, used in a variety of in vivo biomedical applications such as targeted drug delivery, where it is possible to transport drugs or medicine to a specific region in the body [5,6]. Biomolecular-tagged magnetic beads can also be used in vitro to divide, sort or separate different biomolecules [7–9]. Magnetic micro-sensors can then be used to count, detect or estimate the concentration of biomolecules tagged to magnetic beads. The ⇑ Corresponding author. Address: 4700 King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia. Tel.: +966 50 158 2953; fax: +966 2 802 0140. E-mail address: [email protected] (C.P. Gooneratne). 0167-9317/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.mee.2010.12.068
potential advantages of this technique are that results can be obtained much faster and cheaper than with traditional analytical methods, such as polymerase chain reaction, culture and colony counting or immunological based methods such as enzyme linked immunosorbent assay. Hence, integrated microfluidic devices with magnetic micro-sensors have a great potential to be used as accurate and rapid diagnostic tools in medicine. The focus of this paper is on attracting, trapping and guiding magnetic beads towards a sensing site with the aid of an external magnetic field. Manipulation is achieved by the magnetic force exerted on magnetic beads. The magnetic field can be produced by permanent micro-magnets or micro-electromagnets [10]. Even though permanent micro-magnets produce strong localized magnetic fields, micro-electromagnets offer flexibility with respect to magnitude, frequency and waveform of the magnetic field. Furthermore, micro-magnets are more expensive to fabricate than micro-electromagnets. Some research has been conducted to attract and trap magnetic beads using micro-electromagnets [11–13]. However, their complex patterns and designs, in some cases also combined with magnetic pillars, are unsuitable for precisely manipulating a few magnetic beads and integration with magnetic micro-sensors. A simple, inexpensive, planar square-loop microstructure is presented in this paper to manipulate 2 lm diameter magnetic beads and guide them towards a sensing site. The novelty of the presented system lies in the unique method of guiding magnetic beads. A spin-valve type giant magnetoresistance (GMR) sensor [14] is proposed as the sensing element in the sensing area.
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2. Technique of magnetic bead manipulation 2.1. Magnetic force on magnetic beads Conducting wires in the micrometer range are able to generate large magnetic field gradients due to their small widths and high aspect ratios [15]. In the presence of magnetic beads the large magnetic field gradients generate forces on the beads. These forces are used to attract, trap and guide the magnetic beads to the target destination. The force on a magnetic bead can be expressed by [16],
~ F m ¼ rðm BÞ;
ð1Þ
1 V Dv ~ rB2 Fm ¼ 2 l0
ð2Þ
where m is the magnetic moment of the bead, V is the volume of the bead, v is the difference of magnetic susceptibility between the bead and the medium, l0 is the permeability of vacuum (1.25 106 N A2) and B is the amplitude of the applied magnetic field in Tesla. To attract and trap magnetic beads the magnetic forces produced by the fields must be larger than the most dominant force acting against the manipulation of beads, the drag force, Fd (due to fluid motion). If the microfluidic medium and the radius of the magnetic bead are known Fd can be controlled by the velocity of the medium [16]. 2.2. Simulation results The finite element method (FEM) was used to simulate (with COMSOL, Inc. software) a three-dimensional (3-D) square loop, as
shown in Fig. 1a. A side-length of the loop is 150 lm, with a width of 10 lm and thickness 0.5 lm. Finite element analysis is critical in optimizing the design of square-shaped conducting micro-loops. It can be seen from Fig. 1a that the magnetic field is highest at the surface of the micro-loop (shown by the light streamlines) and decreases when moving away from the surface of the loop (streamlines get darker). The magnetic field is also more uniform at the center of the square loop. This can be explained further by referring to Fig. 1b. Fig. 1b shows that not only does the magnetic field increase when moving towards the surface of the loop, but the gradient of the magnetic field also increases. Hence, the magnetic force on the magnetic beads is at a maximum on the surface of the square loop. Therefore, the magnetic beads would primarily be attracted to the perimeter of the square loops. Another important consideration is the critical current density based on the electromigration limit of the conducting metal. A silicon chip can tolerate current densities up to 1010 A/cm2, hence the limiting factor in micro design is no longer the melting point but rather the occurrence of electromigration. These simulations were performed at current densities of 2 106 A/cm2, which is lower than the current density of silicon as well as the standard electromigration limit of 5 107 A/cm2 for aluminum. Fig. 2a shows the magnetic field for three conducting square loops with different side lengths. Fig. 2b shows the magnetic forces produced by the conducting micro-loops on a magnetic bead of 2 lm diameter. It can be seen that the magnetic field and hence the force dampens very quickly when moving away in the x-direction from the surface of loops. Hence, the magnetic force is only effective in the vicinity of the micro-loop. According to the results obtained by simulation, magnetic beads can be attracted from a
Fig. 1. Finite element simulation of a square micro-loop that is used for magnetic bead manipulation. (a) 3-D model showing magnetic field in a current carrying square loop, and (b) cross-section of the square loop showing magnetic field contour lines.
C.P. Gooneratne et al. / Microelectronic Engineering 88 (2011) 1757–1760
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Fig. 2. Simulation results for three square loops with side lengths 30, 50 and 70 lm. (a) Magnetic field distribution on the surface of loops and, (b) corresponding forces on a magnetic bead of 2 lm diameter.
distance as far as 10 lm. Hence, the distance between the inner side length of a given conducting square loop and the outer side length of an adjacent micro-loop was chosen to be 10 lm. 3. Design and fabrication of microstructure The schematic of the device design for the integrated squareshaped micro-loops and GMR sensors is shown in Fig. 3. The microstructure consists of five planar square-shaped conducting micro-loops. The number of loops depends on the area from which magnetic beads need to be attracted, trapped and guided to the sensing area as well as the size of the bead to be attracted. The loops are designed in such a way that a current can be applied to them independently. Upon sequential application of current, starting from the outermost square loop, beads are directed to move from the outermost to the innermost square loop or the other way around. The speed with which the beads move towards the sensing zone can be controlled by the speed with which current is switched between the loops. The sensing area consists of two magnetic field sensors located directly under the innermost square loop. The square loops are separated from the sensing elements by a thin passivation layer. The active sensing elements detect the induced magnetic field from the magnetic beads, tangential to the sensor surface. The sensing elements are connected to form a half-Wheatstone bridge circuit, i.e. the two active elements are connected to two reference resistors located away from the experimental area, for optimum noise suppression. The planar square-shaped conducting micro-loops were fabricated by photolithography and lift-off on a Silicon (Si) wafer. Commercial software (CoventorWare) was used to design the patterns of the micro-loop structures. A side length of the innermost square loop was 30 lm and loops were repeated with a distance of 10 lm between adjacent loops. The width of the conducting
Fig. 3. Proposed microstructure. (a) Schematic of the device design and, (b) SEM image of sensing elements.
loops was set to 10 lm. Pre-baking was performed at 150 °C on the Si wafer to improve the adhesion of the photoresist to the Si surface. A UV light exposure tool was used to transfer the microloop patterns to the photoresist on the Si wafer. After development, a 500 nm thick layer of aluminum was sputtered on top of the resist. Lift-off was then performed in a solution of acetone. A commercial GMR sensor provided by Austrian Institute of Technology (AIT) as shown in Fig. 3b is proposed as the sensing element. Amongst the different magnetic sensors GMR structures are generally preferred for application in biodiagnostics, since only a small magnetic field is needed to change the resistance and they have an advantage in size, power, cost and thermal stability with respect to search coil, fluxgate, SQUID, Hall and spin resonance sensors [17]. Furthermore, GMR sensors are also ideal for low cost applications since they are easily energized by applying a constant current and the output voltage is a measure of the magnetic field. 4. Experimental analysis Experiments were performed with five square-shaped conducting micro-loops and 2 lm diameter magnetic beads from ChemicellÒ. The original weight density of 100 mg/ml was diluted by adding de-ionized (DI) water resulting in weight densities ranging from 1 to 10 mg/ml. One microliter of magnetic beads was injected
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Fig. 4. Experimental results with square aluminum micro-loops with width 10 lm and thickness 500 nm. (a) No current applied to loops, (b) magnetic beads being attracted, trapped at the outermost loop and, (c–e) transported through corresponding adjacent loops to, (f) the innermost loop, where the GMR sensing elements are located.
onto the square loop area. Fig. 4 shows how magnetic beads can be attracted, trapped and guided towards the sensing area. In Fig. 4a no current was applied and the magnetic beads flowed past the microstructure. A current of 50 mA was then applied to the square loops sequentially starting from the outermost loop as shown in Fig. 4b, and ending with the innermost loop where the GMR sensing elements are located (Fig. 4f). The results show that magnetic beads can be attracted from an area of radius 109 lm to an area of 30 lm. The advantage of this novel arrangement of loops is that the number of square loops can be increased or decreased according to the area from which the magnetic beads are supposed to be attracted, trapped and guided towards the GMR sensing area. Hence, magnetic bead manipulation from millimeter to nanometer precision is feasible. 5. Conclusion A novel electromagnetic microstructure was presented in this paper for transporting magnetic beads towards a sensing site. Numerical analysis was performed to calculate magnetic field gradients and the corresponding magnetic forces exerted on magnetic beads. Based on the numerical results planar square-shaped conducting microstructures were designed and fabricated. Experimental results showed that the fabricated square micro-loop system could not only attract and trap magnetic beads but also guide them towards the sensing area. Once the magnetic beads are concentrated to the vicinity of the sensing area, magnetic field sensors like GMR sensors could be used to detect the presence of the beads. Further experiments will be performed with different magnetic bead weight densities to obtain a relationship between the magnetic bead weight density and GMR output signal.
Acknowledgments The authors gratefully acknowledge Dr. Volker Hoeink and Dr. Hubert Brückl of the Austrian Institute of Technology for their help in GMR sensor fabrication. The authors thank Dr. Zhihong Wang, Dr. Xianbin Wang and Mr. Basil Chew for their help in microfabrication. Special mention is due to Mr. Guodong Li for his help with electronic circuitry for the project. The authors also thank Dr. Jian Ren and Dr. Xian Yu for their help in chemical preparation and material characterization, respectively. References [1] N. Pamme, Lab Chip 6 (2006) 24. [2] J. Rife, M.M. Miller, P.E. Sheehan, C.R. Tamanaha, M. Tondra, L.J. Whitman, Sens. Actuators A 107 (3) (2003) 209. [3] C.C. Berry, A.S.G. Curtis, J. Phys. D Appl. Phys. 36 (2003) R198. [4] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, J. Phys. D Appl. Phys. 36 (2003) R167. [5] O.V. Salata, J. Nanobiotechnol. 2 (2004) 3, doi:10.1186/1477-3155-2-314773155-2-3. [6] A.K. Gupta, M. Gupta, Biomaterials 26 (2005) 3995. [7] A.S. Arbab, G.T. Yocum, H. Kalish, E.K. Jordan, S.A. Anderson, A.Y. Khakoo, E.J. Read, J.A. Frank, Blood 104 (4) (2004) 1217. [8] C. Delgratta, S. Dellapenna, P. Battista, L. Didonato, P. Vitullo, G. Romani, S. Diluzio, Phys. Med. Biol. 40 (1995) 671. [9] N.C. Tansil, Z. Gao, Nano Today 1 (1) (2006) 28. [10] M. Bu, T.B. Christensen, K. Smistrup, A. Wolff, M.F. Hansen, Sens. Actuators A 145–146 (2008) 430. [11] A. Rida, V. Fernandez, M.A.M. Gijs, Appl. Phys. Lett. 83 (12) (2003) 2396. [12] C. Derec, C. Wilhelm, J. Servais, J.C. Servais, Microfluid. Nanofluid. 8 (2010) 123. [13] Q. Ramadan, V. Samper, D.P. Poenar, C. Yu, Biosens. Bioelectron. 21 (2006) 1693. [14] S.X. Wang, G. Li, IEEE. Trans. Mag. 44 (2008) 1687. [15] X.J.A. Jannsen, L.J. Van Ijzendoorn, M.W.J. Prins, Biosens. Bioelectron. 23 (6) (2008) 833. [16] C. Liu, T. Stakenborg, S. Peeters, L. Lagae, J. Appl. Phys. 105 (2009) 102014. [17] C.H. Smith, R.W. Schneider, Sensors 16 (9) (1999) 76.
Contents lists available at ScienceDirect
Microelectronic Engineering journal homepage: www.elsevier.com/locate/mee
A planar conducting microstructure to guide and confine magnetic beads to a sensing zone Chinthaka P. Gooneratne ⇑, Cai Liang, Jürgen Kosel Division of Physical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
a r t i c l e
i n f o
Article history: Available online 25 December 2010 Keywords: Magnetic beads Microstructure Microfluidics GMR sensor
a b s t r a c t A novel planar conducting microstructure is proposed to transport and confine magnetic micro/nano beads to a sensing zone. Manipulation and concentration of magnetic beads are achieved by employing square-shaped conducting micro-loops, with a few hundred nano-meters in thickness, arranged in a unique fashion. These microstructures are designed to produce high magnetic field gradients which are directly proportional to the force applied to manipulate the magnetic beads. Furthermore, the size of the microstructures allows greater maneuverability and control of magnetic beads than what could be achieved by permanent magnets. The aim of the microstructures is to guide magnetic beads from a large area and confine them to a smaller area where for example quantification would take place. Experiments were performed with different concentrations of 2 lm diameter magnetic beads. Experimental results showed that magnetic beads could be successfully guided and confined to the sensing zone. Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction The past decade has seen an unprecedented increase in interest for utilizing magnetic beads in microfluidic devices [1]. Magnetic beads can be seamlessly integrated into systems on a chip due to, their micro/nano size, large specific surface areas available for binding biomolecules, being independent of reagent chemistry or photo-bleaching as well as being biocompatible with no toxicity index [2,3]. Superparamagnetic-type magnetic beads have attracted a lot of attention in recent times [4]. They do not have a magnetic moment in the absence of an external magnetic field but become magnetized once an external magnetic field is applied. Hence, unlike ferromagnetic materials, they do not exhibit a remanent magnetization. This not only prevents the agglomeration of magnetic beads but also enables an external magnetic field to control the beads remotely. Hence, magnetic beads are for example, used in a variety of in vivo biomedical applications such as targeted drug delivery, where it is possible to transport drugs or medicine to a specific region in the body [5,6]. Biomolecular-tagged magnetic beads can also be used in vitro to divide, sort or separate different biomolecules [7–9]. Magnetic micro-sensors can then be used to count, detect or estimate the concentration of biomolecules tagged to magnetic beads. The ⇑ Corresponding author. Address: 4700 King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia. Tel.: +966 50 158 2953; fax: +966 2 802 0140. E-mail address: [email protected] (C.P. Gooneratne). 0167-9317/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.mee.2010.12.068
potential advantages of this technique are that results can be obtained much faster and cheaper than with traditional analytical methods, such as polymerase chain reaction, culture and colony counting or immunological based methods such as enzyme linked immunosorbent assay. Hence, integrated microfluidic devices with magnetic micro-sensors have a great potential to be used as accurate and rapid diagnostic tools in medicine. The focus of this paper is on attracting, trapping and guiding magnetic beads towards a sensing site with the aid of an external magnetic field. Manipulation is achieved by the magnetic force exerted on magnetic beads. The magnetic field can be produced by permanent micro-magnets or micro-electromagnets [10]. Even though permanent micro-magnets produce strong localized magnetic fields, micro-electromagnets offer flexibility with respect to magnitude, frequency and waveform of the magnetic field. Furthermore, micro-magnets are more expensive to fabricate than micro-electromagnets. Some research has been conducted to attract and trap magnetic beads using micro-electromagnets [11–13]. However, their complex patterns and designs, in some cases also combined with magnetic pillars, are unsuitable for precisely manipulating a few magnetic beads and integration with magnetic micro-sensors. A simple, inexpensive, planar square-loop microstructure is presented in this paper to manipulate 2 lm diameter magnetic beads and guide them towards a sensing site. The novelty of the presented system lies in the unique method of guiding magnetic beads. A spin-valve type giant magnetoresistance (GMR) sensor [14] is proposed as the sensing element in the sensing area.
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2. Technique of magnetic bead manipulation 2.1. Magnetic force on magnetic beads Conducting wires in the micrometer range are able to generate large magnetic field gradients due to their small widths and high aspect ratios [15]. In the presence of magnetic beads the large magnetic field gradients generate forces on the beads. These forces are used to attract, trap and guide the magnetic beads to the target destination. The force on a magnetic bead can be expressed by [16],
~ F m ¼ rðm BÞ;
ð1Þ
1 V Dv ~ rB2 Fm ¼ 2 l0
ð2Þ
where m is the magnetic moment of the bead, V is the volume of the bead, v is the difference of magnetic susceptibility between the bead and the medium, l0 is the permeability of vacuum (1.25 106 N A2) and B is the amplitude of the applied magnetic field in Tesla. To attract and trap magnetic beads the magnetic forces produced by the fields must be larger than the most dominant force acting against the manipulation of beads, the drag force, Fd (due to fluid motion). If the microfluidic medium and the radius of the magnetic bead are known Fd can be controlled by the velocity of the medium [16]. 2.2. Simulation results The finite element method (FEM) was used to simulate (with COMSOL, Inc. software) a three-dimensional (3-D) square loop, as
shown in Fig. 1a. A side-length of the loop is 150 lm, with a width of 10 lm and thickness 0.5 lm. Finite element analysis is critical in optimizing the design of square-shaped conducting micro-loops. It can be seen from Fig. 1a that the magnetic field is highest at the surface of the micro-loop (shown by the light streamlines) and decreases when moving away from the surface of the loop (streamlines get darker). The magnetic field is also more uniform at the center of the square loop. This can be explained further by referring to Fig. 1b. Fig. 1b shows that not only does the magnetic field increase when moving towards the surface of the loop, but the gradient of the magnetic field also increases. Hence, the magnetic force on the magnetic beads is at a maximum on the surface of the square loop. Therefore, the magnetic beads would primarily be attracted to the perimeter of the square loops. Another important consideration is the critical current density based on the electromigration limit of the conducting metal. A silicon chip can tolerate current densities up to 1010 A/cm2, hence the limiting factor in micro design is no longer the melting point but rather the occurrence of electromigration. These simulations were performed at current densities of 2 106 A/cm2, which is lower than the current density of silicon as well as the standard electromigration limit of 5 107 A/cm2 for aluminum. Fig. 2a shows the magnetic field for three conducting square loops with different side lengths. Fig. 2b shows the magnetic forces produced by the conducting micro-loops on a magnetic bead of 2 lm diameter. It can be seen that the magnetic field and hence the force dampens very quickly when moving away in the x-direction from the surface of loops. Hence, the magnetic force is only effective in the vicinity of the micro-loop. According to the results obtained by simulation, magnetic beads can be attracted from a
Fig. 1. Finite element simulation of a square micro-loop that is used for magnetic bead manipulation. (a) 3-D model showing magnetic field in a current carrying square loop, and (b) cross-section of the square loop showing magnetic field contour lines.
C.P. Gooneratne et al. / Microelectronic Engineering 88 (2011) 1757–1760
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Fig. 2. Simulation results for three square loops with side lengths 30, 50 and 70 lm. (a) Magnetic field distribution on the surface of loops and, (b) corresponding forces on a magnetic bead of 2 lm diameter.
distance as far as 10 lm. Hence, the distance between the inner side length of a given conducting square loop and the outer side length of an adjacent micro-loop was chosen to be 10 lm. 3. Design and fabrication of microstructure The schematic of the device design for the integrated squareshaped micro-loops and GMR sensors is shown in Fig. 3. The microstructure consists of five planar square-shaped conducting micro-loops. The number of loops depends on the area from which magnetic beads need to be attracted, trapped and guided to the sensing area as well as the size of the bead to be attracted. The loops are designed in such a way that a current can be applied to them independently. Upon sequential application of current, starting from the outermost square loop, beads are directed to move from the outermost to the innermost square loop or the other way around. The speed with which the beads move towards the sensing zone can be controlled by the speed with which current is switched between the loops. The sensing area consists of two magnetic field sensors located directly under the innermost square loop. The square loops are separated from the sensing elements by a thin passivation layer. The active sensing elements detect the induced magnetic field from the magnetic beads, tangential to the sensor surface. The sensing elements are connected to form a half-Wheatstone bridge circuit, i.e. the two active elements are connected to two reference resistors located away from the experimental area, for optimum noise suppression. The planar square-shaped conducting micro-loops were fabricated by photolithography and lift-off on a Silicon (Si) wafer. Commercial software (CoventorWare) was used to design the patterns of the micro-loop structures. A side length of the innermost square loop was 30 lm and loops were repeated with a distance of 10 lm between adjacent loops. The width of the conducting
Fig. 3. Proposed microstructure. (a) Schematic of the device design and, (b) SEM image of sensing elements.
loops was set to 10 lm. Pre-baking was performed at 150 °C on the Si wafer to improve the adhesion of the photoresist to the Si surface. A UV light exposure tool was used to transfer the microloop patterns to the photoresist on the Si wafer. After development, a 500 nm thick layer of aluminum was sputtered on top of the resist. Lift-off was then performed in a solution of acetone. A commercial GMR sensor provided by Austrian Institute of Technology (AIT) as shown in Fig. 3b is proposed as the sensing element. Amongst the different magnetic sensors GMR structures are generally preferred for application in biodiagnostics, since only a small magnetic field is needed to change the resistance and they have an advantage in size, power, cost and thermal stability with respect to search coil, fluxgate, SQUID, Hall and spin resonance sensors [17]. Furthermore, GMR sensors are also ideal for low cost applications since they are easily energized by applying a constant current and the output voltage is a measure of the magnetic field. 4. Experimental analysis Experiments were performed with five square-shaped conducting micro-loops and 2 lm diameter magnetic beads from ChemicellÒ. The original weight density of 100 mg/ml was diluted by adding de-ionized (DI) water resulting in weight densities ranging from 1 to 10 mg/ml. One microliter of magnetic beads was injected
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Fig. 4. Experimental results with square aluminum micro-loops with width 10 lm and thickness 500 nm. (a) No current applied to loops, (b) magnetic beads being attracted, trapped at the outermost loop and, (c–e) transported through corresponding adjacent loops to, (f) the innermost loop, where the GMR sensing elements are located.
onto the square loop area. Fig. 4 shows how magnetic beads can be attracted, trapped and guided towards the sensing area. In Fig. 4a no current was applied and the magnetic beads flowed past the microstructure. A current of 50 mA was then applied to the square loops sequentially starting from the outermost loop as shown in Fig. 4b, and ending with the innermost loop where the GMR sensing elements are located (Fig. 4f). The results show that magnetic beads can be attracted from an area of radius 109 lm to an area of 30 lm. The advantage of this novel arrangement of loops is that the number of square loops can be increased or decreased according to the area from which the magnetic beads are supposed to be attracted, trapped and guided towards the GMR sensing area. Hence, magnetic bead manipulation from millimeter to nanometer precision is feasible. 5. Conclusion A novel electromagnetic microstructure was presented in this paper for transporting magnetic beads towards a sensing site. Numerical analysis was performed to calculate magnetic field gradients and the corresponding magnetic forces exerted on magnetic beads. Based on the numerical results planar square-shaped conducting microstructures were designed and fabricated. Experimental results showed that the fabricated square micro-loop system could not only attract and trap magnetic beads but also guide them towards the sensing area. Once the magnetic beads are concentrated to the vicinity of the sensing area, magnetic field sensors like GMR sensors could be used to detect the presence of the beads. Further experiments will be performed with different magnetic bead weight densities to obtain a relationship between the magnetic bead weight density and GMR output signal.
Acknowledgments The authors gratefully acknowledge Dr. Volker Hoeink and Dr. Hubert Brückl of the Austrian Institute of Technology for their help in GMR sensor fabrication. The authors thank Dr. Zhihong Wang, Dr. Xianbin Wang and Mr. Basil Chew for their help in microfabrication. Special mention is due to Mr. Guodong Li for his help with electronic circuitry for the project. The authors also thank Dr. Jian Ren and Dr. Xian Yu for their help in chemical preparation and material characterization, respectively. References [1] N. Pamme, Lab Chip 6 (2006) 24. [2] J. Rife, M.M. Miller, P.E. Sheehan, C.R. Tamanaha, M. Tondra, L.J. Whitman, Sens. Actuators A 107 (3) (2003) 209. [3] C.C. Berry, A.S.G. Curtis, J. Phys. D Appl. Phys. 36 (2003) R198. [4] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, J. Phys. D Appl. Phys. 36 (2003) R167. [5] O.V. Salata, J. Nanobiotechnol. 2 (2004) 3, doi:10.1186/1477-3155-2-314773155-2-3. [6] A.K. Gupta, M. Gupta, Biomaterials 26 (2005) 3995. [7] A.S. Arbab, G.T. Yocum, H. Kalish, E.K. Jordan, S.A. Anderson, A.Y. Khakoo, E.J. Read, J.A. Frank, Blood 104 (4) (2004) 1217. [8] C. Delgratta, S. Dellapenna, P. Battista, L. Didonato, P. Vitullo, G. Romani, S. Diluzio, Phys. Med. Biol. 40 (1995) 671. [9] N.C. Tansil, Z. Gao, Nano Today 1 (1) (2006) 28. [10] M. Bu, T.B. Christensen, K. Smistrup, A. Wolff, M.F. Hansen, Sens. Actuators A 145–146 (2008) 430. [11] A. Rida, V. Fernandez, M.A.M. Gijs, Appl. Phys. Lett. 83 (12) (2003) 2396. [12] C. Derec, C. Wilhelm, J. Servais, J.C. Servais, Microfluid. Nanofluid. 8 (2010) 123. [13] Q. Ramadan, V. Samper, D.P. Poenar, C. Yu, Biosens. Bioelectron. 21 (2006) 1693. [14] S.X. Wang, G. Li, IEEE. Trans. Mag. 44 (2008) 1687. [15] X.J.A. Jannsen, L.J. Van Ijzendoorn, M.W.J. Prins, Biosens. Bioelectron. 23 (6) (2008) 833. [16] C. Liu, T. Stakenborg, S. Peeters, L. Lagae, J. Appl. Phys. 105 (2009) 102014. [17] C.H. Smith, R.W. Schneider, Sensors 16 (9) (1999) 76.