Magnetic Droplet Manipulation Platforms for Nucleic Acid Detection at the Point of Care DONG JIN SHIN 1 and TZA-HUEI WANG 1,2,3,4,5 1 Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; 2 Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA; 3 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; 4 Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; and 5 108 Latrobe, 3400 N Charles St, Baltimore, MD 21218, USA (Received 28 February 2014; accepted 19 June 2014; published online 10 July 2014) Associate Editor Tingrui Pan oversaw the review of this article. Abstract—This review summarizes recent developments in the use of magnetically actuated droplets in point-of-care molecular diagnostic platforms. We discuss the fundamentals of magnetic droplet manipulation and the various modes of actuation. The balance of forces acting on a droplet during transport and particle extraction, as well as the devices and instrumentation developed to perform these operations will be presented and discussed. Furthermore, we review some of the recent advances on the diagnostic applications of platforms utilizing magnetic manipulation for genetic assess- ment of biological samples. Keywords—Magnetofluidics, Droplet manipulation, Electro- magnetic actuation, Surface patterning, DNA extraction, Real-time PCR. INTRODUCTION Recent advances in bioanalytical techniques have enabled researchers to develop assays that are both simple and robust. These developments have paved the path towards integrated platforms designed to perform all aspects of molecular diagnostic assays, from sample preparation to detection, on a single device. Taking advantage of these advancements, commercial devel- opment of plug-and-play benchtop platforms has already made significant progress in recent years, as demonstrated in products such as Cepheid GeneXpert platform 62 and BioFire FilmArray platform. 5 Mean- while, efforts to further miniaturize assays for mobile medicine have also led to shifting paradigms in aca- demic research towards approaches such as paper- based microfluidic devices, 61 capillary pump-driven microfluidic devices 16,19 and droplet-based plat- forms. 16,32 In addition to the traditional benefits of microfluidics like reduced sample consumption and integration, point-of-care diagnostic platforms should also consider factors such as sample preparation, simple end-user operation and portable instrumenta- tion. Among these approaches, droplet-based tech- niques are of particular interest since aqueous reagents are readily scalable in a droplet format without radical modification to biochemical processes, which makes them easily adaptable to a wide range of current and future benchtop assays. Droplet microfluidic platforms have emerged under various formats, and can be broadly categorized under open-surface and channel-based formats. Further- more, platforms may be categorized based on the mode of droplet or particle manipulation, some of which include magnetic, 2,7,13,27,29,32,34,36,37,39,43,44,52,63–65,67 dielectrophoretic (DEP), 15,22,53 electrowetting-on- dielectric (EWOD) 8,14,20,30,38,47,48,50,55 and optical 12,35 approaches. This review focuses specifically on open- surface magnetic droplet platforms that utilize mag- netic forces on particles as a means of both droplet and particle manipulation. This is in contrast to other droplet platforms utilizing EWOD and DEP as the primary mechanism for droplet handling, where the incorporation of magnetic particles requires an auxil- iary mode of actuation for magnetic manipulation. Magnetic particles are regularly utilized in biochemical assays as solid phase substrates for analyte capture and purification, which highlights the importance of mag- netic manipulation in these platforms. Magnetic droplet platforms are particularly well-suited to nucleic acid-based assays for two reasons. Firstly, nucleic acid Address correspondence to Tza-Huei Wang, 108 Latrobe, 3400 N Charles St, Baltimore, MD 21218, USA. Electronic mail: biom- ems123@gmail.com, thwang@jhu.edu Annals of Biomedical Engineering, Vol. 42, No. 11, November 2014 (Ó 2014) pp. 2289–2302 DOI: 10.1007/s10439-014-1060-2 0090-6964/14/1100-2289/0 Ó 2014 Biomedical Engineering Society 2289