Rolled-up Sensors for Fluidics

The development of conceptually new tools for bioanalytics and therapy combining low cost, high sensitivity, and the ability of real time detection is of tremendous interest for modern diagnostics and medicine. The range of modern diagnostics and therapeutic techniques, relying on magnetic micro and nanoparticles, continuously increases [Red07, Bec08]. After decades of careful studies of their properties and biocompatibility, magnetic particles have entered commercial applications, helping to detect nucleic acids and proteins, to treat cancer, or to enhance the magnetic resonance imaging (MRI) contrast. Currently, novel concepts for drug and gene delivery, based on magnetofection [Sch02], as well as magnetic cell sorting [Rob11] are under intensive investigation. Apart from being considered as a highly efficient instrument for bio-labeling and detection, magnetic particles represent a powerful tool for bio chemical analysis, e.g. for magnetic immunoassays [MAG]. Therefore, the need for an integration of low magnetic field sensing devices into biomedical systems is greatly increasing.

Previous efforts have mostly concentrated on the static detection of magnetic nanoparticles [Li06]. This method implies the changes of the measured electrical signal of the device caused by a magnetic particle, immobilized at the surface of the sensor. However, for advanced high throughput analysis of biochemical substances (e.g. drug screening), large amount of fluidic samples containing functional nanoparticles, living cells or emulsion droplets have to be tested in a short time. There are two possible configurations for the development of an efficient magnetic biosensing platform: The first one (and traditionally employed) is based on a movable magnetic sensor, referred to as a micro-plate reader (Figure 1(a)) [MPR]. This geometry is rather convenient in operation, but stays expensive and energy consuming due to the precise micropositioning elements incorporated.

Figure 1: (a) State of the art biosensing platform: micro-plate reader [MPR-1]. (b) Proposed concept: two functional elements (magnetic sensor and valve) are integrated into a rolled-up architecture to realize detection and sorting on a single chip. This work is carried out in collaboration with Dr. Larysa Baraban (chair “Material Science and Nanotechnology” of the TU Dresden). Panel (b) is adopted from [Mön11, Lin13].

A novel alternative solution represents an in flow detection of the magnetic micro and nanoparticles with a stationary magnetic sensor. When integrated on a microfluidic chip [Kas04], such a biosensing platform can provide high reproducibility, precise control over the injected chemical content and would be available at a low price. The approach to realize this concept is sketched in Figure 1(b): Nano or microscopic magnetic particles carrying the specific functional groups or being uptaken by the living cells are detected and counted, while travelling from an inlet reservoir through a fluidic channel to an outlet reservoir. Potentially, a series of a magnetic sensor device can be integrated in the channels, and, whenever a magnetic object passes by, its magnetic stray field is detected electrically through a magnetoresistive effect. As the magnetic moment of the nanoparticles is rather low, the magnetic sensor device should be sensitive to small magnetic fields, which can be achieved by devices relying on the giant magnetoresistive (GMR) effect [Par95, Pan04]. To this end, planar magnetic sensors were already incorporated in microfluidic channels enabling a dynamic detection of magnetic particles [She05, Jia06]. We went further in the development and reported on the integration of a GMR sensor based on [Py/Cu] multilayers directly into a rolled-up fluidic channel with a diameter of 60 µm and demonstrated the performance of this functional element for the in-flow detection of ferromagnetic CrO2 nanoparticles embedded in a biocompatible polymeric shell (Figure 2) [Mön11].

Figure 2: (a) Schematics revealing the main concept of a rolled-up magnetic sensor for in-flow detection of magnetic objects. (b) Photograph of the complete device in a planar arrangement before the rolling process. The insets in (b) show the optical micrographs of the planar and rolled-up sensors. (c) Magnetic particles detection: Time evolution of the sensor output signal measured while magnetic particles pass the rolled-up sensor. The figure is adopted from [Mön11].

The advantages of this device are intriguing: (i) the sensor covers part of the inner wall of the fluidic channel and as such is positioned in closest possible vicinity to the flowing objects, which increases the signal to noise ratio of the device compared to the case when the sensor is positioned outside the channel. (ii) The rolled-up geometry makes the sensor sensitive to magnetic stray fields of the particles under study in virtually all directions (isotropic sensitivity) which is superior compared to the planar counterparts. Isotropic sensitivity allows avoiding implementation of an external magnet to align the magnetic moment of the particle with respect to the direction of the highest sensitivity of the sensor. Both these aspects are crucial for an efficient and successful in-flow detection of magnetic objects (Figure 2(c)).

References:
[Red07] S. T. Reddy et al., Nature Biotechnology 25, 1159 (2007).
[Bec08] D. Bechet et al., Trends in Biotechnology 26, 612 (2008).
[Sch02] F. Scherer et al., Gene Therapy 9, 102 (2002).
[Rob11] D. Robert et al., Lab Chip 11, 1902 (2011).
[MAG] http://www.magnisense.com/
[Li06] G. Li et al., Sens. Actuators A: Phys. 126, 98 (2006).
[MPR] http://www.directindustry.de/industrie-hersteller/microplate-reader-79467.html
[MPR-1] http://www.biochrom.co.uk/product/43/biochrom-anthos-multiread-400-microplate-reader.html
[Kas04] A. S. Kashan et al., Proc. Natl. Acad. Sci. U.S.A. 102, 9745 (2004).
[She05] W. Shen et al., Appl. Phys. Lett. 86, 253901 (2005).
[Jia06] Z. Jiang et al., J. Appl. Phys. 99, 08S105 (2006).
[Mön11] I. Mönch et al., ACS Nano 5, 7436 (2011).
[Lin13] G. Lin et al., Nature Scientific Reports 3, 2548 (2013).

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This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration
under grant agreement no 306277.