Fully Integrated Complementary Metal Oxide Semiconductor (CMOS) Bio-Assay Platform
We present a post-processed 2.5mm x 2.5mm 0.18um Complementary Metal Oxide Semiconductor (CMOS) platform that leverages the advantages of super-paramagnetic bead labeling to integrate on-chip the label separation and detection functionalities required for high sensitivity bio-assays. The surfaces of the CMOS chip and of the magnetic beads are functionalized with bio-chemicals complementary to a target analyte. In a sandwich capture format, the presence of the target analyte will strongly bind 4.5um magnetic bead labels to the surface of the chip. The undesired background signal is minimized by the removal of the unbound magnetic beads from the detection array via magnetic forces generated on-chip. The remaining strongly bound magnetic beads are respectively magnetized and detected by an array of 128 stacked micro-coil/Hall sensor elements. This single chip solution does not require any external components like pumps, valves or electromagnets and is capable of detecting purified Human antibodies down to concentrations of 100pg/ml as well as anti-Dengue antibodies in human serum samples.
A whole blood sample preparation system based on membrane filtration alleviates the need for centrifugation and can be readily combined with the assay platform into a high performance, Point-of-Need (PON) In-Vitro Diagnostic (IVD) device.
The present prototype relies on an electronic reader for controlling the assay and reporting results. Implementing this function on the bio-sensor front-end enables a very simple design consisting of only the bio-sensor and an attached results display. Such low-cost, easy-to-use, high performance devices are needed for lowering health costs through more decentralized distribution of medical care.