Ex-vivo multi-dimensional system for the separation and isolation of cells, vesicles, nanoparticles, and biomarkers

摘要

Devices and techniques are described that involve a combination of multidimensional electrokinetic, dielectrophoretic, electrophoretic and fluidic forces and effects for separating cells, nanovesicles, nanoparticulates and biomarkers (DNA, RNA, antibodies, proteins) in high conductance (ionic) strength biological samples and buffers. In disclosed embodiments, a combination of continuous and/or pulsed dielectrophoretic (DEP) forces, continuous and/or pulsed field DC electrophoretic forces, microelectrophoresis and controlled fluidics are utilized with arrays of electrodes. In particular, the use of chambered DEP devices and of a properly scaled relatively larger electrode array devices that combines fluid, electrophoretic and DEP forces enables both larger and/or clinically relevant volumes of blood, serum, plasma or other samples to be more directly, rapidly and efficiently analyzed. The invention enables the creation of “seamless” sample-to-answer diagnostic systems and devices. The devices and techniques described can also carry out the assisted self-assembly of molecules, polymers, nanocomponents and mesoscale entities into three dimensional higher order structures.

主权项

1. A process for separating elutable nanoscale analytes from larger entities in a high conductance sample, the process comprising:
(a) applying a high conductance biological sample of >100 mS/m comprising whole blood, serum, plasma, urine or saliva, to an alternating current (AC) electrokinetic device comprising a plurality of non-sputtered alternating current (AC) electrodes; and (b) with an alternating current, selectively energizing the electrodes and establishing dielectrophoretic (DEP) high field and dielectrophoretic (DEP) low field regions in the high conductance sample, whereby AC electrokinetic effects separate elutable nanoscale analytes from larger entities in the high conductance sample by isolating elutable nanoscale analytes in the dielectrophoretic (DEP) high field region and isolating larger entities in the dielectrophoretic (DEP) low field region.