The ability to rapidly detect cell free circulating (cfc) DNA, cfc-RNA, exosomes and other nanoparticulate disease
biomarkers as well as drug delivery nanoparticles directly in blood is a major challenge for nanomedicine. We now
show that microarray and new high voltage dielectrophoretic (DEP) devices can be used to rapidly isolate and detect
cfc-DNA nanoparticulates and nanoparticles directly from whole blood and other high conductance samples (plasma,
serum, urine, etc.). At DEP frequencies of 5kHz-10kHz both fluorescent-stained high molecular weight (hmw) DNA,
cfc-DNA and fluorescent nanoparticles separate from the blood and become highly concentrated at specific DEP highfield
regions over the microelectrodes, while blood cells move to the DEP low field-regions. The blood cells can then
be removed by a simple fluidic wash while the DNA and nanoparticles remain highly concentrated. The hmw-DNA
could be detected at a level of <260ng/ml and the nanoparticles at <9.5 x 109 particles/ml, detection levels that are well
within the range for viable clinical diagnostics and drug nanoparticle monitoring. Disease specific cfc-DNA materials
could also be detected directly in blood from patients with Chronic Lymphocytic Leukemia (CLL) and confirmed by
PCR genotyping analysis.
We have performed separation of bacterial and cultured cancer cells from peripheral human blood in microfabricated electronic chips by dielectrophoresis. The isolated cells were examined by staining the nuclei with fluorescent dye followed by laser induced fluorescence imaging. We have also related DNA and RNA from the isolated cells electrically and detected specific marker sequences by DNA amplification followed by electronic hybridization to immobilized capture probes. Efforts toward the construction of a 'laboratory-on- a-chip' system will be presented which involves the selection of DNA probes, dyes, reagents and prototyping of the fully integrated portable instrument.
The integration of optoelectronic and electronic components from different origins and substrates makes possible many advanced systems in diverse applications in photonics. To this end, various hybrid integration technologies including flip-chip bonding, epitaxial lift-off and direct bonding, substrate removal and “applique” bonding, microrobotic pick and place, and self-assembly methods have been explored. In this paper, we will briefly describe and evaluate these approaches for their applications in optoelectronics and focus on a new micro-assembly technology that can pick, place, and bond many devices of different origins and dimensions simultaneously in a parallel fashion on very large surfaces. We will present some of our preliminary results demonstrating the feasibility of this DNA-assisted micro-assembly technique.
The heterogeneous integration of optoelectronic, electronic, and micro-mechanical components from different origins and substrates makes possible many advanced systems in diverse applications. Besides the monolithic integration approach, which is the basis for the success of today's silicon industry, various hybrid integration technologies have been explored. These include flip-chip bonding, micro-robotic placement, epitaxial lift-off and direct bonding, substrate removal and bonding, and several self-assembly methods. In this paper, we describe the results of our monolithic integration effort involving a 2 by 2 optoelectronic switching circuit and an 8 by 8 active-pixel sensor array on GaAs substrates, and a 16 by 16 spatial light modulator array produced by flip-chip bonding of III-V multi-quantum-well (MQW) modulators and silicon driver circuits. We also present our preliminary experimental results on the self-assembly of small inorganic devices coated with DNA polymers with self- recognition properties.