Microfluidics-based immunoassays

Roper, M.G., Shackman, J.G., Dahlgren, G.M., Kennedy, R.T., Microfluidic chip for continuous monitoring of hormone secretion from live cells using an electrophoresis-based immunoassay. Anal. Chem. 2003, 75, 4711—4717. 

Lee M, Lee K, Kim KH, Oh KW, Choo J (2012) SERS-based immunoassay using a gold array-ensembled gradient microfluidic chip. Lab Chip 12 3720-3727... 

Zimmerman M, Delamarche E, Wolf M, Hunziker P (2005) Modeling and optimizatitm of high sensitivity, low vol microfluidic based surface immunoassays. Bimned Microdevices 7(2) 99-110... 

Zyomyx (Hayward, GA) has developed the Zyomyx human cytokine biochip that uses microfluidics to measure 30 different human cytokines simultaneously. Biosite (San Diego, GA) markets commercial microfluidic chip-based immunoassay for clinical applications. Multiplexed assays using fluorescent microspheres/beads in Lab-on-Ghip format manufactured by Becton-Dickinson (Franklin, NJ), Diasorin (Stillwater, MN), and Luminex Gorp. (Austin, TX) are also available for use in clinics. 

Mu, X., Zhang, L., Chang, S., Cui, W., Zheng, Z., 2014. Multiplex microfluidic paper-based immunoassay for the diagnosis of hepatitis C virus infection. Anal. Chem. 86, 5338-5344. 

The versatility of luminescence goes beyond intensity-, wavelength- and kinetic-based measurements. Fluorescence polarization (or anisotropy) is an additional parameter still largely unexplored for optical sensing yet widely used in Biochemistry to study the interaction of proteins, the microfluidity of cell membranes and in fluorescence immunoassays. Although only a few optosensors based on luminescence polarization measurements can be found in the literature, elegant devices have recently been reported to measure chemical parameters such as pFI or O2 even with the bare eye41. 

As an example of microchip-based electrochemical immunoassays, we describe here the protocol established for the analysis of interleukin IB by enzyme linked immunosorbent assay (ELISA) with amperometric detection at the sub-pM level in DiagnoSwiss microfluidic chip called Immuchip . 

Luo Y, Yu F, Zare RN (2008) Microfluidic device for immunoassays based on surface plasmon resonance imaging. Lab Chip 8 694—700... 

In addition to commercially production, a great deal of research and development work on biochips has been going on both in industry and in academia. Genomic analysis of DNA and RNA continues to be the focus of interest, but more and more effort is being spent on proteomic analysis of proteins and peptides. Several enzyme assays and immunoassays designed based on microarray-based systems with simple microfluidic control are close to commercialization. They can be a vital tool in clinic diagnostics, drug discovery, and biomedical research. 

Lim, C. T., and Zhang Y. (2007) Bead-based microfluidic immunoassays The next generation. Biosens. Bioelectron., 22, 1197-1204... 

The first immunoassay performed in a capillary driven system was reported in 1978 [67]. Based on this technique, the commonly known over-the-counter pregnancy test was introduced into the market in the middle of the 80 s. Today, this microfluidic platform is commonly designated as a lateral flow test (LAT) [14]. Other terms are test strip , immunochromatographic strip , immunocapillary tests or sol particle immunoassay (SPIA) [68]. Astonishingly, hardly any publications from a microfluidic point of view or in terns of material classification exist, and apparently many company secrets are kept unpublished [69]. 

Abstract. Microfluidics is key to miniaturize bio-chemical and biomedical methods and processes into chip based technology. Basics of electrokinetic microfluidics will be reviewed first. Three types of lab-on-a-chip devices, PCR lab-on-a-chip, flow cytometer lab-on-a-chip and immunoassay lab-on-a-chip are discussed here. The working principle, key microfluidic processes and the current status of these lab-on-a-chip devices are reviewed. 

Internal reflection spectroscopy (IRS) is another promising optical detection for immunoassay [64]. Llobera et al. reported PDMS-based multiple internal reflection systems comprised of self-alignment systems, lenses, microfluidic channels, and mirrors. It is noteworthy that the LOD was lowered down to 41 nM using an air mirror [49]. 

---