Method and apparatus for forming a homeostatic loop employing an aptamer biosensor

Abstract

A novel architecture solid-state biosensor for label-free detection of vascular endothelial growth factor (VEGF) hybridization is presented. The new device is realized by forming a matrix array of parallel capacitors, thus allowing the realization of low-cost, portable, fully integrated devices. The detection mechanism is based on an electrochemical binding of circulating VEGF to an immobilized VEGF aptamer; whereby binding of these two compounds modulates the threshold voltage of a novel circuit, changing the impedance (capacitance) of the circuit. This novel circuit is further characterized by an electrode coded with a p-Si substrate, enhancing the affinity between the VEGF molecules and the aptamer. An apparatus forming a fluid cell is configured so as to enable the flow for delivering VEGF samples onto the active surface of the chip. The device has an array of parallel capacitors which act as an integrated, individual counter-electrode, computational apparatus which employs the sensory output over the time domain so as to enable detection, reporting and formation of a homeostatic loop for VEGF measurements. Moreover, this detector is able to provide an accurately measured and quantifiable rate of change of the VEGF molecules in- vivo, providing real time feedback of this important biomarker which may be used to measure response of the tumor to delivered chemotherapeutic agents and biological response modifiers (BRMs) for the purpose of determining tumor burden.

Description

technical field [0001] The present invention relates to chemical biosensors. More specifically, the present invention relates to immobilization of parallel plate chemical biosensor and capacitor arrays and methods of fabricating them. Background technique [0002] Vascular endothelial growth factor (VEGF) plays a key role during normal angiogenesis as well as in pathological angiogenesis that occurs in many diseases including cancer. By using the humanized monoclonal antibody bevacizumab (Avastin, Genentech / Roche) and the two kinase inhibitors sorafenib (Nexavar) targeting VEGF receptor (VEGFR) tyrosine kinase; Bayer) and initial efforts to block VEGF with sunitinib (Sutent, Pfizer) are beginning to show promise in human cancer patients, highlighting the importance of optimizing VEGF blockade. Human tumor growth and metastasis depend on de novo formation of blood vessels to reach and nourish the hypoxic tumor microenvironment. Neovascularization is highly regulated by spe...

AI Technical Summary

Problems solved by technology

Many of these forms are undergoing clinical studies to evaluate their potential to treat various forms of human cancer, but the power of such studies is limited by the fact that real-time in vivo measurements of VEGF levels and VEGF transduction tropism are not readily available

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