Digital Microfluidic Magnetic
Separation for Particle-Based
Immunoassays
- Publication date
- Publisher
Abstract
We introduce a new format for particle-based immunoassays
relying
on digital microfluidics (DMF) and magnetic forces to separate and
resuspend antibody-coated paramagnetic particles. In DMF, fluids are
electrostatically controlled as discrete droplets (picoliters to microliters)
on an array of insulated electrodes. By applying appropriate sequences
of potentials to these electrodes, multiple droplets can be manipulated
simultaneously and various droplet operations can be achieved using
the same device design. This flexibility makes DMF well-suited for
applications that require complex, multistep protocols such as immunoassays.
Here, we report the first particle-based immunoassay on DMF without
the aid of oil carrier fluid to enable droplet movement (i.e., droplets
are surrounded by air instead of oil). This new format allowed the
realization of a novel on-chip particle separation and resuspension
method capable of removing greater than 90% of unbound reagents in
one step. Using this technique, we developed methods for noncompetitive
and competitive immunoassays, using thyroid stimulating hormone (TSH)
and 17β-estradiol (E2) as model analytes, respectively. We show
that, compared to conventional methods, the new DMF approach reported
here reduced reagent volumes and analysis time by 100-fold and 10-fold,
respectively, while retaining a level of analytical performance required
for clinical screening. Thus, we propose that the new technique has
great potential for eventual use in a fast, low-waste, and inexpensive
instrument for the quantitative analysis of proteins and small molecules
in low sample volumes