S-H. Duh, J. Thornton, P.T. Kissinger, E.T. Chen
Advanced Biomimetic Sensors Inc.,
Keywords: nanobiomimetic memristor/memcapacitor, neuronal synapse, slow-wave-sleeping, voltage sensor and amperometric sensor, reagent-less, acetyl coenzyme A
Summary:Acetyl co-enzyme A (AcCoA) is a leading substrate in a large variety of enzyme-catalyzed reactions, such as for choline acetyltransferase and acetylcholinesterase. They are critical to energy production, metabolism, memory, cell proliferation and early childhood development. AcCoA is central to biological acetylation reactions. Unbalanced regulation of AcCoA led to many diseases, such as diabetes, cancer, coronary disease, Alzheimer’s. Common commercial test methods lack of sensitivity and precision that due to the protein interference plus the time consuming assay has been burdensome. We developed a nanostructured biomimetic sensor for direct measure sub pM concentrations of AcCoA under the conditions of free from antibody and radio labeling tracers, and is reagent-less. The gold sensor ships have nano island structure membrane with cross-linked polymers and have function groups mimicking Fibroblast Growth Factor Receptor 1 (FGFR1). The signal changes of AcCoA over a wide concentrations range between 2 pM to 0.3µM were measured by the chronoamperometry (CA) method having a linear range from 2 pM to 0.4 nM. The value of Detection of Limits (DOL) is 1.2x10-12M/cm2. AcCoA spiked milk specimens were measured with a recovery value of 103%, and the method produced an imprecision error of less than 2% (n=12) by using human milk samples. The impact of human milk and organic milk samples upon the neuronal synapse action /resting potential pulses toward the sensor were studied with or without fixed 60 pM AcCoA at slow-wave-sleeping (SWS) and 250 Hz, respectively. The results indicate human milk having 100-fold sensitive to detect AcCoA than organic milk designated for infants using a double step chronopotentiometry (DSCPO) method at SWS. This work was built upon our previous works: Nanostructured Memristor Sensor Mimics Acetylcholinesterase (ACHE) Active Sites in The Gorge for fM Detection of Acetylcholine, NSTi-Nanotech, 2, 200-203, 2014. A Nanobiomimetic Neuronal Memcapacitor Serves as a Voltage Sensor and an Amperometry Sensor for Reagent-less Direct Detection of Sub pM Soluble Amyloid-beta. Biotech, Biomaterials and Biomedical: TechConnect Briefs, 172-175, 2015. Nanobiomimetic Memcapacitor Memory Devices Identify Circadian Rhythm Dysfunction and Predict Early Signs of “Epilepsy” Using Reentrant Energy-Sensory Images, Advanced Manufacturing, Electronics and Microsystems: TechConnect Briefs, 200-203, 2015. Acetylcholine Repairs the Amyloid-beta Damage on Brain Circuitry and Memory Loss from a “Mutated Biomimetic Acetylcholinesterase” Neuronal Memcapacitor During Slow-Wave Sleeping, Advanced Manufacturing, Electronics and Microsystems: TechConnect Briefs, 226-229, 2015. The new accomplishments are:1) Orders of magnitudes increased the detection sensitivity compared with the data reported in literature for AcCoA;2) The precision also improved a magnitude using milk specimen; 3). Our assay is superior compared with the conventional assay in shortened test time by 104-fold, Reagent-less without environment contamination, easy and burden-free benefit for workers; simple and portable;4). It will open a wide market application.