IEEE TRANSACTIONS ON MAGNETICS, VOL. 50, NO. 11, NOVEMBER 2014 4401304 Microfluidics for the Rapid Detection of Pathogens Using Giant Magnetoresistance Sensors Georgios Kokkinis 1 , Susana F. Cardoso 2 , Filipe Arroyo Cardoso 2 , and Ioanna Giouroudi 1 1 Institute of Sensor and Actuator Systems, Vienna University of Technology, Vienna 1040, Austria 2 INESC Microsystems and Nanotechnologies and IN, Lisbon 1000-029, Portugal 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. Index Terms— Biosensor, diagnostics, giant magnetoresistance (GMR), pathogens. I. I NTRODUCTION T HE remarkable promise of microfluidics in combination with magnetic methods opens the path to exceptional advances in point-of-care pathogen diagnostics and on-site food and water quality control. Pathogens are infectious microorganisms that cause diseases to their host, e.g., bacteria, viruses, fungi, and parasites 1,2,3,4 . Most of the existing laboratory techniques to identify sus- pected pathogens use culturing of these microorganisms to grow colonies large enough to identify. Nevertheless, there exist methods which do not require a large amount of sample and provide rapid identification, such as immunological tests (e.g., ELISA immunoassays), nucleic-acid-based diagnostics and microfluidics 5,6 [1]–[4]. Yet, these methods can be techno- logically complex, require established laboratory infrastructure and well-trained personnel, or do not provide information on the pathogen load. Moreover, even though they are highly sensitive and specific, false positive and negative results may occur. These results may be caused by improper sample storage or treatment, improper washing methods, or reagent deterioration. The reported microfluidic diagnostic systems up to date either require complex on-chip designs, fluorescence or quantum dot labeling, nucleic acid amplification, or continuous flow [5]–[7]. In this paper, we propose a simple microfluidic diagnostic platform which combines magnetic isolation (filtering mech- Manuscript received March 10, 2014; revised April 23, 2014; accepted May 9, 2014. Date of current version November 18, 2014. Corresponding author: I. Giouroudi (e-mail: ioanna.giouroudi@tuwien.ac.at). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TMAG.2014.2323991 1 http://www.unaids.org/en/ 2 http://www.preventchildhoodinfluenza.org/ 3 http://globalviral.org/ 4 http://www.un-influenza.org/ 5 http://www.alere.com 6 http://www.micronics.net anism) and magnetic detection of pathogens without flow, without the need to use fluorophores or quantum dot labels, and without complicated microfluidic structures. II. WORKING PRINCIPLE Our microfluidic system consists of two microfluidic chan- nels; reference and detection channel. The sample under investigation (e.g., water) is mixed with antibody functional- ized microparticles (MPs) (which are commercially available, see [8]). The bacteria (e.g., Escherichia coli) are specifi- cally captured by the MPs due to the affinity between the antibodies and the surface antigens of the bacteria forming compounds-loaded MPs (LMPs). Afterward, the resulting fluid is transported into the detection channel. The reference channel is filled with the same, plain (nonfunctionalized) MPs. The magnetically tagged bacteria and the plain MPs are accelerated inside the detection and reference microchannels by embedded aluminum conducting microstructures, which are controlled by a programmable microprocessor [9]–[13]. The advantage of these microstructures over an external permanent magnet is that they ensure a better control of the magnetic field (by controlling the applied current), hence allowing uniformity regarding the acceleration of the MPs and LMPs. This way, a fully automated solution for the application and control of the magnetic field is also offered, since the current power supply can be controlled by a PC and the relevant software. In addition to that, the position of the conductive microstructures, coated with a thin passivation layer, can be controlled in the micrometer range. Two giant magnetoresistance (GMR) sensors are located near the inlet and outlet of the reference and the detection microchannels. When MPs and LMPs are introduced in the microchannels a change in the electrical resistance of the first GMR sensor, located near the inlet, occurs. Then, the MPs and LMPs are accelerated by means of the externally applied magnetic force through the conducting microstructures. When 0018-9464 © 2014 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.