Nanobiomimetic Superlattice Superconductive/Memristive Organometallic Devices at Room Temperature Serve as Chronoamperometric Sensors for sub fg/mL Collagen-1 Detection in Human Serum

E.T. Chen, J.T. Thornton, P.T. Kissinger, S-H. Duh
Advanced Biomimetic Sensors, Inc.,
United States

Keywords: organometallic superconductor, nanobiomimetic superlattice structure, superconductive/memristive, probe-free and label-free


Superconductive/Memristive devices have potential applications in supercomputing and in health industry was proposed in literature. Clinically detection range at low concentration for collagen-1 is difficult to accomplish due to the denaturing of protein Matrix Matelloprotinase-2 (MMP-2). An unique type of nanostructured superconductive/memristive devices, as Sensor 1, was developed for mimicking the active state of protein Matrix Matelloprotinase-2 (MMP-2) without cystein in the membrane on gold chips compared with an active nature protein Sensor 2 made by MMP-2 cross-linked with multiple polymers after denaturing. Sensor 1 was made by multiple-layer cross-linking membranes with embedded zinc ions on gold chips. A Cyclic Voltammetry (CV) method, a Chronoamperometry method (CA) and a Double Step Chronopotentiometry (DSCPO) (the voltage) method was conducted under antibody-free and tracers-free conditions. Sensor 1 produced superconducting current at room temperature in the presence of collagen-1 using the CV method. Sensor 1’s memristive hysteresis i-V curves were observed compared with Sensor 2, does not have the characteristics. The Detection of Limits (DOL) using Sensor 1 are 0.43 pg/mL/cm2 (14 fg/mL for this sensor) over the analytical range 5 fg/mL-200 ng/mL (linear range from 5fg/mL to 100 ng/mL) with a Pooled relative standard deviation (PRSD) of 0.05% at the high end and 0.5% at the low end in PBS using the CA method. The recovery results obtained from collagen-1-spiked human finger capillary whole blood (CPWB) serum specimens are 96.4% (s.d., 3.4%) with the imprecision of 4.9% and 0.8% at 2.5 pg/mL and 166 ng/mL level, respectively by Sensor 1 using spiked CPWB serum specimens. The activated protein sensor 2 was able to detect collagen-1 in CPWB specimens with an analytical range between 0.05 ng/mL to 100 ng/mL with the PRSD values of 0.5% and 0.2% for action and resting potential by the voltage method, respectively. Our accomplishments are based on our prior works: Nanobiomimetic Memristor/memcapacitors’ Function as a Voltage Sensor for Direct and Reagent-free Detection of sub pg Lipopolysaccharide (LPS) in Different Types of Milks for Infants, Sensors, Diagnostics & Imaging, TechConnect Briefs, 4, 140-143, 2016. Organic Nanobiomimetic Memristive/Memcapacitive Devices Ultrasensitive Direct Detect Matrix Matelloproteinase-2 in Human Serum, Biotech, Biomaterials and Biomedical, TechConnect Briefs, 271-274, 2017. Partially listed patents: Nanopore array structured devices for biosensing and energy storage, US 8,641,876, 2014. Nanobiomimetic Supercapacitors with High Rate High Energy Storage, US 9,443,665, 2015. Nanostructured biomimetic device for detecting a cancer cell or cancer cells US 9534999, Jan. 2017. The accomplishments are:1) Revolutionarily solved the collagen detection problem at the low end by developing an unique superconductive/memristive device and side-by-side compared with the activated protein sensor. 2). It reduced the assay burden and orders of magnitude increased the detection sensitivity; 3) our innovative approach by utilizing collagen’s unique role in superconducting at room temperature offers practical utility; 4) Reagent-free and probe-free advantages overcome environment contamination; 5) Simple and portable. It will open wide market applications. 6). the robust performance of the superconductive/memristive devices has provided a foundation for further automation.