**4. Droplet-based micro-magnetofluidics**

While the detection of electrochemical methods like ampere- and potentiometric methodologies are based on alterations of electric conductivities of liquid phases in their surroundings, the detection of further physical properties, not directly visible by mentioned technologies, give rise to additional functionalities in microfluidic

μTAS applications. One prominent example depicts the research field of micromagnetofluidics, the combination of microfluidics and magnetism, where the detection of magnetic fields of magnetically active or responsive liquids or magnetic species, demonstrate high potential in various applications. In this research field, one distinguishes between fluid control and manipulation in open channels and confined channels. Here, the utilization, manipulation and detection of magnetic species like magnetic nano- and microparticles in micro-magnetofluidics demonstrate big potential especially in biological, chemical and medical analysis. These species can act as carriers for biological and biochemical markers and molecules, act as immobilization bases and markers for quantitative detection and analysis. In this section, the closedchannel micro-magnetofluidics will be in focus. Further information about open channel micro-magnetofluidics, or digital micro-magnetofluidics, can be found in refs. [62–64]. Micro-magnetofluidics represents an active research field in the last two decades, facilitating various microfluidic procedures like mixing, particle focusing, stream manipulation, droplet generation, pumping and cell sorting [65, 66]. A big step in improvement of these systems as μTAS were first reports in 2005 about integration of micro-scale magnetoresistive sensors in microfluidic channels for analysis of passing magnetic liquids, *e.g.* magnetic micro [67]-and nanoparticles [68]. The working principle of magnetoresistive (MR) sensors is based on the change of their electric resistance by external magnetic fields. Especially in μTAS applications, in order to achieve maximum information output, vast amounts of relevant data points are collected due to high-throughput analysis at high sampling rates. To tackle this challenge of big data treatment, machine-learning algorithms are on the rise in current μTAS sensor applications and examples on this integration will be addressed in the section.

In the following, four types of magnetic field sensors and their microfluidic integration will be covered, namely anisotropic magnetoresistive (AMR), giant magnetoresistive (GMR), tunnel magnetoresistance (TMR) and planar Hall effect (PHE) sensors. Typically, the magnetization in AMR sensors is located in plane and sensor elements are fabricated as thin 2D layers (**Figure 7a**). Although AMR effect is about 2% only, due to their simplicity in fabrication, low noise and robustness, AMR sensors are broadly used in different industrial applications. In contrary to AMR effect, which can be observed in single layers of ferromagnetic material, the giant magnetoresistive (GMR) effect is specific to multilayer stacks of alternating metallic ferromagnetic and nonmagnetic layers. The electric resistance of this stack is changed significantly (about 50%) when the magnetization of adjacent layers is changing from antiparallel (in zero magnetic field) to parallel in an applied magnetic field (**Figure 7b**). The tunnel magnetoresistance (TMR) describes stacks of ferromagnetic, antiferromagnetic and insulator materials and its electrical resistance changes when magnetization of free ferromagnetic layer switches from antiparallel to parallel. In

#### **Figure 7.**

*(a) The anisotropic magnetoresistive effect (AMR) describes resistance alterations upon presence of magnetic fields based on intra-band electron scattering of ferromagnetic materials. (b) the giant magnetoresistive (GMR) effect in multilayer stacks of ferromagnetic and metallic layers. (c) Tunneling magnetoresistance is measured between the ferromagnetic layers across the isolation layer (cyan). (d) Planar hall effect (PHE) leads to variations of electrical conductivity by in-plane magnetic fields.*

## *Real-Time Tracking of Individual Droplets in Multiphase Microfluidics DOI: http://dx.doi.org/10.5772/intechopen.106796*

contrary to GMR, TMR sensors are measured perpendicular to the layer stack through the isolation layer (**Figure 7c**). The working principle of Planar Hall effect (PHE) sensors is based on anisotropic magnetoresistance [69] and spin Hall magnetoresistance [70] but, unlike AMR sensors, resistance alterations are measured transverse to the supplying electric current in electric anisotropically conducting thin films. When measuring the transverse voltage drop developed of this thin film, a planar Hall effect can be observed where the current will not flow collinearly with the voltage gradient. It experiences a transverse deflection towards the high conductivity axis, which results in an equilibrium transverse voltage drop (**Figure 7d**).

First reports date back to 2005, where principles and different types of MR sensors were presented and integrated into microfluidic systems, forming the base of micro-magnetofluidics, *i.e.* GMR [71–73], TMR sensors [67, 68], AMR sensors [74, 75] and PHE sensors [76]. Here, MR sensor were usually patterned using optical lithography on rigid substrates like silicon or glass with feature sizes in the μm range. First evaluations concentrated on detection of micron-sized particles. The next step in the evolution of MR sensors and micro-magnetofluidics was the addition of emulsion-based fluidic systems, *i.e.* microfluidic droplets. The first publications on the topic were focused on the detection and characterization of magnetic nanoparticle (MNP) based solutions, *i.e.* ferrofluids [77]. These superparamagnetic liquids broaden the field of application for micro-magnetofluidics, *e.g.* improved point-ofcare diagnostics by better capture capabilities of MNPs for isolation of rare biomarkers and molecules, their ultrasensitive detection down to single-molecule sensitivity as well as drug discovery via remote control of individual droplets. With respect to MR sensor utilization for droplet-based micro-magnetofluidics, GMR sensors (spin valves and multilayers) are still one of the preferred sensor technology. Recent publications demonstrate advantages of PHE sensors due to their low limit of detection (down to 0.04 mg/cm3 ferrofluid mass) and low noise (5 pT/√Hz at 10 Hz) and thus their capability to measure outside of the channel geometry [78]. In the following, a detailed journey from the beginning of droplet-based magnetofluidics to present applications and integration with various types of MR sensors will be presented. The section is structured based on the microfluidic channel design to give an overview, starting from tubing-based channels (millifluidics), polymer-based channel systems (microfluidics) followed by insights and outlook to ultra-small channels in the nanometer regime (nanofluidics).
