Mobile diagnostics: next-generation technologies for in vitro diagnostics.

The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

Visualization and label-free quantification of microfluidic mixing using quantitative phase imaging.

Microfluidic mixing plays a key role in various fields, including biomedicine and chemical engineering. To date, although various approaches for imaging microfluidic mixing have been proposed, they provide only quantitative imaging capability and require exogenous labeling agents. Quantitative phase imaging techniques, however, circumvent these problems and offer label-free quantitative information about concentration maps of microfluidic mixing. We present the quantitative phase imaging of microfluidic mixing in various types of polydimethylsiloxane microfluidic channels with different geometries; the feasibility of the present method was validated by comparing it with the results obtained by theoretical calculation based on Fick's law.

Optoelectrofluidic printing system for fabricating hydrogel sheets with on-demand patterned cells and microparticles.

This paper presents a novel optoelectrofluidic printing system that facilitates not only the optoelectrofluidic patterning of microparticles and mammalian cells but also the harvesting of the patterned microparticles encapsulated within poly(ethylene glycol) dicarylate (PEGDA) hydrogel sheets. Although optoelectrofluidic technology has numerous advantages for programmable and on-demand patterning and the feasibility of manipulating single microparticles, practical applications using existing laboratory infrastructure in biological and clinical research fields have been strictly restricted due to the impossibility of recovering the final patterned product. In order to address these harvesting limitations, PEGDA was employed to utilize optoelectrofluidic printing. The Clausius-Mossotti factor was calculated to investigate the dielectrophoretic mobility of the microparticle and the cell in the PEGDA precursor solution. As a proof of concept, three basic controllabilities of the optoelectrofluidic printing system were characterized: the number of microparticles, the distance between the microparticle columns, and the ratio of two different microparticles. Furthermore, the optoelectrofluidic patterning and printing of human liver carcinoma cells (HepG2) were demonstrated in 5 min with a single-cell level of resolution. The appropriate ranges of frequency were experimentally defined based on the calculated result of the dielectrophoretic mobility of HepG2 cells. Finally, optoelectrofluidically cell-patterned hydrogel sheets were successfully recovered under a highly viable physiological condition.

Microarray-integrated optoelectrofluidic immunoassay system.

A microarray-based analytical platform has been utilized as a powerful tool in biological assay fields. However, an analyte depletion problem due to the slow mass transport based on molecular diffusion causes low reaction efficiency, resulting in a limitation for practical applications. This paper presents a novel method to improve the efficiency of microarray-based immunoassay via an optically induced electrokinetic phenomenon by integrating an optoelectrofluidic device with a conventional glass slide-based microarray format. A sample droplet was loaded between the microarray slide and the optoelectrofluidic device on which a photoconductive layer was deposited. Under the application of an AC voltage, optically induced AC electroosmotic flows caused by a microarray-patterned light actively enhanced the mass transport of target molecules at the multiple assay spots of the microarray simultaneously, which reduced tedious reaction time from more than 30 min to 10 min. Based on this enhancing effect, a heterogeneous immunoassay with a tiny volume of sample (5 µl) was successfully performed in the microarray-integrated optoelectrofluidic system using immunoglobulin G (IgG) and anti-IgG, resulting in improved efficiency compared to the static environment. Furthermore, the application of multiplex assays was also demonstrated by multiple protein detection.

Optoelectrofluidic enhanced immunoreaction based on optically-induced dynamic AC electroosmosis.

We report a novel optoelectrofluidic immunoreaction system based on electroosmotic flow for enhancing antibody-analyte binding efficiency on a surface-based sensing system. Two conventional indium tin oxide glass slides are assembled to provide a reaction chamber for a tiny volume of sample droplet (∼5 µL), in which the top layer is employed as an antibody-immobilized substrate and the bottom layer acts as a photoconductive layer of an optoelectrofluidic device. Under the application of an AC voltage, an illuminated light pattern on the photoconductive layer causes strong counter-rotating vortices to transport analytes from the bulk solution to the vicinity of the assay spot on the glass substrate. This configuration overcomes the slow immunoreaction problem of a diffusion-based sensing system, resulting in the enhancement of binding efficiency via an optoelectrofluidic method. Furthermore, we investigate the effect of optically-induced dynamic AC electroosmotic flow on optoelectrofluidic enhancement for surface-based immunoreaction with a mathematical simulation study and real experiments using immunoglobulin G (IgG) and anti-IgG. As a result, dynamic light patterns provided better immunoreaction efficiency than static light patterns due to effective mass transport of the target analyte, resulting in an achievement of 2.18-fold enhancement under a growing circular light pattern compared to the passive mode.

In situ dynamic measurements of the enhanced SERS signal using an optoelectrofluidic SERS platform.

A novel active surface-enhanced Raman scattering (SERS) platform for dynamic on-demand generation of SERS active sites based on optoelectrofluidics is presented in this paper. When a laser source is projected into a sample solution containing metal nanoparticles in an optoelectrofluidic device and an alternating current (ac) electric field is applied, the metal nanoparticles are spontaneously concentrated and assembled within the laser spot, form SERS-active sites, and enhance the Raman signal significantly, allowing dynamic and more sensitive SERS detection. In this simple platform, in which a glass slide-like optoelectrofluidic device is integrated into a conventional SERS detection system, both dynamic concentration of metal nanoparticles and in situ detection of SERS signal are simultaneously possible with only a single laser source. This optoelectrofluidic SERS spectroscopy allows on-demand generation of 'hot spots' at specific regions of interest, and highly sensitive, reliable, and stable SERS measurements of the target molecules in a tiny volume (∼500 nL) of liquid sample without any fluidic components and complicated systems.