On-chip magnetic separation platform. Magnetic beads are pulled to the detection in the center of the trench etched in by magnetic forces generated by current passing through the concentration conductor. Nonspecifically bound beads are pulled aside by magnetic forces resulting from current passing through the separation conductors embedded along the ridges of the trench.
CMOS postprocessing steps. (a) Standard five metal layer CMOS IC. (b) A RIE step is used to create trenches in the . Photoresist is used to protect the other portions of the IC (connection pads, CMOS circuitry, etc.) while top metal polygons are used to define the trenches. Metal 2 polygons are used as etch-stop layers for the RIE, protecting the concentration conductors buried below the trench. (c) A wet etch is used to remove the exposed aluminum. Note that the connection pads are still protected by the photoresist. (d) The photoresist is removed and 10 nm of Cr followed by 30 nm of Au are evaporated on the sensor area through a shadow mask.
SEM of postprocessed IC. Dynal M-450, wide, superparamagnetic beads are dried on the surface and a SEM is taken of the surface of the IC using a Hitachi TM1000.
CMOS IC and assay cartridge. (a) Micrograph of a CMOS IC with magnetic bead concentration and separation capabilities. The top metal layer is used as an etch mask to define the trenches in which the assays are performed. (b) Picture of the assembled device, where the IC is flip-chip bonded to the bottom of a PCB housing a vial.
Cross section of trench etched in . (a) As the magnetic beads settle to the surface of the IC due to gravity, current is run through the concentration conductor at the bottom of the trench to ensure that the beads land in the center. (b) After the beads have been concentrated on the surface of the IC, current is passed through the integrated separation conductors running along the ridge of the trench to generate a magnetic force capable of removing all the nonspecifically bound beads, a process referred to as on-chip magnetic separation.
Mechanical leverage. The magnetic force applied to the lever arm of height translates into a magnified force on the last immunological tether of length (Ref. 5).
Lumped equivalent thermal circuit. The two forms of heat dissipation modeled are transfer through the backside of the IC and storage in the thermal capacitance of the fluid inside the well. A magnetic separation power applied for 30 s will increase the temperature of the fluid in the well by above ambient temperature.
Magnetic bead binding chemistry. Surface polyclonal goat IgG specific to the region of human IgG is passively adsorbed on the gold surface. Human IgG antigen is added, followed by the primary biotinylated monoclonal goat IgG specific to the region of the human IgG antigen. Last, the streptavidin-coated Dynal bead labels are added.
Control assays results. Serial tenfold dilutions of purified human IgG from to 100 pg/ml were assayed to compare the biochemical sensitivity and dynamic range of ELISA on polystyrene, ELISA on gold, and off-chip magnetic bead labeled assays. The experiment at each dilution was repeated eight times and the error bars correspond to .
Magnetic bead concentration. The time lapse micrograph shows the beads settling onto the surface of the IC as 2 mA of current are run through the concentration conductors under the center of the wide trench. The shaded rectangle delineates the wide detection area in which the magnetic beads are counted.
On-chip magnetic bead separation. Micrographs of a trench before (left) and after (right) magnetic separation are shown for 0, 1, and 10 ng/ml concentrations of human IgG antigen. The separation current is alternated between the left and right sides of the trench at frequency for .
On-chip assay results. The number of beads remaining in the detection area after magnetic separation for serial tenfold dilution of purified human IgG is presented.
Fully integrated assay platform. Magnetic beads are pulled atop Hall sensors by magnetic forces generated by current passing through the microcoils embedded underneath the center of the trench etched in . Nonspecifically bound beads are pulled aside by magnetic forces resulting from current passing through the separation conductors embedded along the ridges of the trench. Last, the specifically bound beads are magnetized by the microcoil and detected by Hall sensors also embedded below the center of the trench (Ref. 2).
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