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Development of a chemical reaction sensor array platform for label-free, real-time kinetic analysis of enzyme-substrate reactions to enable high-throughput drug discovery

Award Number: R44TR003250
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Development of a chemical reaction sensor array platform for label-free, real-time kinetic analysis of enzyme-substrate reactions to enable high-throughput drug discovery - Project Summary Global expenditures by pharmaceutical companies for research and development continue to increase each year with a current estimate of $1B USD and upwards of 15 years to develop a new drug. Drug discovery efforts are critical to the downstream success of candidate selection and relies heavily on high-throughput screening (HTS) to identify viable leads. Current methods for HTS drug discovery assays, such as fluorescence-, or luminescence-based methods, suffer from inherent technical drawbacks and limitations that result in false results leading to failed programs. Additionally, the majority of current HTS methods are not amendable to ultra high- throughput and use end-point assays as opposed to real-time kinetic approaches that can provide a more thorough assessment of molecular interactions. The use of real-time kinetic assays and higher throughput in drug discovery programs could greatly enhance success rates while reducing cost and time. INanoBio is developing a novel fully depleted exponentially coupled (FDEC) field effect transistor (FET) biosensor-based nanosensor multiplexed electronic drug discovery platform (nMEDD) for HTS. Our nMEDD platform will offer (i) real time enzymatic reaction monitoring; (ii) ultra-high sensitivity of detection; (iii) ultra HTS scalability; and (iv) high automation compatibility. The FDEC FET sensors electronically monitor changes in charge or potential by directly reacting with ions in solution, thus allowing for the determination of kinetic reaction rates to inform real-time detection and quantitative measurement of the effects of inhibitors or activators on the enzymatic reaction. As an initial validation of the technology platform, we are focusing on developing nMEDD for use in drug discovery for Alzheimer’s disease (AD). Specifically, we will focus on developing assays to monitor tau phosphorylation and dephosphorylation to enable screening for modulators of tau phosphorylation, as cytosolic aggregates of tau have been linked to AD pathology. The overall goal of this Fast-Track program is to develop INanoBio’s nMEDD platform as a HTS method for monitoring enzymatic reactions for drug discovery purposes. To achieve this goal, the Phase I program will be focused on development of a small-scale multiplex sensor and FDEC FET assays for tau phosphorylation and dephosphorylation to validate the performance of the multiplex sensor. Successful completion of Phase I will result in a sensor chip with spacing that is applicable to a 1536-well plate format and is capable of providing a stable response across the chip for detection of tau phosphorylation and dephosphorylation. The Phase II program will focus on further demonstrating the commercial potential of the FDEC FET technology by completing fabrication of an FDEC FET multiplex sensor and detection system for 1536-well detection of phosphorylation and dephosphorylation of tau, in addition to validation of the assay and demonstration of its potential for higher throughput. Successful completion of the proposed program will provide validation of the nMEDD technology for drug discovery to support partnering efforts and inform expansion of the technology into other disease areas.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $1,024,695 )
2023	2023	INANOBIO, INC.	7201 E HENKEL WAY STE 285	SCOTTSDALE	AZ	85255	MARICOPA	USA	National Center for Advancing Translational Sciences	001	3	8/11/2023	NON-COMPETING CONTINUATION	$1,024,700
2023	2020	SPOC PROTEOMICS INC.	7201 E HENKEL WAY STE 285	SCOTTSDALE	AZ	85255	MARICOPA	USA	National Center for Advancing Translational Sciences	000	1	5/15/2023	NEW	-$5
														Subtotal = $1,024,695

Issue Date FY: 2022 ( Subtotal = $974,700 )
2022	2022	INANOBIO, INC.	7201 E HENKEL WAY STE 285	SCOTTSDALE	AZ	85255	MARICOPA	USA	National Center for Advancing Translational Sciences	000	2	8/5/2022	EXTENSION WITH OR WITHOUT FUNDS	$974,700
														Subtotal = $974,700

Issue Date FY: 2020 ( Subtotal = $324,180 )
2020	2020	INANOBIO, INC.	7201 E HENKEL WAY STE 285	SCOTTSDALE	AZ	85255	MARICOPA	USA	National Center for Advancing Translational Sciences	000	1	9/4/2020	NEW	$324,180
														Subtotal = $324,180

Grand Total All Awards = $2,323,575

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Development of a chemical reaction sensor array platform for label-free, real-time kinetic analysis of enzyme-substrate reactions to enable high-throughput drug discovery

Award Number: R44TR003250

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/05/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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