SBIR-STTR Award

Optofluidics Inc. proposes to develop a novel protein-binding assay platform called the BioPrism. The Bioprism is a multiplexable, label-free, bead-based binding assay. The system will be ideal for in vitro molecular diagnostics, therapeutic development and molecular biology research. The need for more cost-effective high throughput assays is ever present in the pharmaceutical industry, which routinely tests millions of compounds in an effort to find a single effective drug ($19.9B Market by 2017). Molecular binding assays are the basis of the booming biomarker in-vitro diagnostics field ($20B in the US by 2014). There are several highly multiplexed bead-based platforms in the market, but these systems require secondary labels which are expensive and add steps to the assay. There are also successful commercial systems that do label-free protein binding measurements; however they have very little or no multiplexing capability. We propose to combine the best elements from both systems into the BioPrism. The BioPrism will use nanoscale optical devices (photonics) developed in the Erickson Lab at Cornell University and currently being commercialized by Optofluidics. Using a microfluidic flow cell, into which a bead-laden sample is injected, the platform can distinguish between bare nanobeads and protein-bound nanobeads using size- based photonic separation. Protein coated nanobeads significantly increase in size due to the small volume of the starting nanobead. By starting with fluorescent nanoparticles of different colors, where each color corresponds to a different probe, the method can be easily multiplexed. The size of the bead will determine whether analytes have bound and the fluorescence of the bead indicates which probe captured a target. In this Phase I project, we will manufacture our BioPrism chips, characterize the system using off-the-shelf nanoparticles, carry out binding assays to detect the binding of mouse IgG and carry out numerical simulations on the device design to optimize performance. In Phase II, we will focus on assay development and the design and construction of a "shippable" BioPrism system.

Public Health Relevance Statement:


Public Health Relevance:
The proposed technology consists of a new type of biology test which is faster and less expensive than current methods. This test could be used by healthcare professionals to diagnose illness, by pharmaceutical companies to develop new drugs and by researchers to study basic biology.

Project Terms:
Affect; Antibodies; assay development; base; Binding (Molecular Function); Biological Assay; Biological Markers; Biology; Caliber; Capsid Proteins; Cells; Color; cost effective; Data; design; design and construction; Detection; Device Designs; Devices; Diagnosis; Diagnostic; Dimensions; DNA; DNA-Binding Proteins; Drug Industry; Elements; Exhibits; experience; Fluorescence; Future; Health Professional; high throughput screening; Immunoglobulin G; In Vitro; Individual; Journals; Kinetics; Label; laser tweezer; Lasers; Letters; Libraries; Licensing; Marketing; Measurement; Measures; Methods; Microfabrication; Microfluidics; Molecular; Molecular Biology; Mus; nanometer; nanoparticle; nanoscale; Nature; novel; Optics; Output; particle; Particle Size; Pattern; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; photonics; Protein Binding; Proteins; public health relevance; Reaction; Relative (related person); Research; Research Personnel; Resolution; Sampling; Scanning; simulation; Solutions; Sorting - Cell Movement; Stream; Surface; System; Techniques; Technology; Testing; therapeutic development; Thick; Time; tool; Universities; Variant

Optofluidics Inc. proposes to develop a near field optical chromatograph, the BioPrism, and apply it to the characterization of particle coating stability in nanomedicine. According to clinicaltrials.gov, about 10% of all clinical trials involv nanoparticles and the National Science Foundation has predicted that nearly half of future pharmaceuticals will have some nanotechnology component. Some of the prime motivations for moving to nanoparticle based drug formulations are the higher activity associated with larger relative surface areas and the ability to stably disperse inherently insoluble hydrophobic materials. Critical to enabling both these potentially revolutionary capabilities is the developmen of stable nanoparticle coatings. Failure to do so results in particle agglomeration, aggregation and ultimately nanotoxicity. As we describe in the proposal through a series of industry reports, quotes from top experts, and specific case studies, there is a distinct lack of instrumentation tha can rapidly assess nanoparticle coatings and the development of such a system could both reduce the time to market for new drugs and increase patient safety. The BioPrism method uses laser light to push particles along the surface of a waveguide and is based on technology licensed from Cornell University and further developed by Optofluidics. Briefly, the surface interaction between the particle and the waveguide affects particle mobility and residence time, enabling separation in the same way as adsorption chromatography. As we demonstrate in the proposal however the use of optical forces to drive the separation process enable a potential order of magnitude increase in size resolution over that possible with existing chromatography systems. This significantly finer resolution provides us with a potentially disruptive advantage, enabling the direct measurement of changes in particle coatings rather than relying on the observation of second order late stage effects, such as agglomeration, like existing instruments do. At the conclusion of this Phase II effort we will have developed a BioPrism cassette that is both validated by our industry partners and collaborators and compatible with our existing instrument product line thereby facilitating our path to market.

Thesaurus Terms:
Adsorption;Affect;Area;Base;Biological Assay;Case Study;Chromatography;Clinical Trials;Commercialization;Cost;Cost Savings;Coupling;Design;Development;Devices;Drug Formulations;Failure (Biologic Function);Flocculation;Foundations;Future;Industry;Industry Collaborators;Industry Partner;Instrument;Instrumentation;Lasers;Lead;Letters;Licensing;Light;Liquid Substance;Marketing;Measurable;Measurement;Measures;Methods;Motivation;Nanodrug;Nanofabrication;Nanomedicine;Nanoparticle;Nanotechnology;Nanotoxicity;Next Generation;Optical Traps;Optics;Particle;Patient Safety;Performance;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Process;Public Health Relevance;Relative (Related Person);Reporting;Research Contracts;Residence;Resolution;Science;Series;Signal Transduction;Site;Solutions;Sorting - Cell Movement;Staging;Stream;Surface;Surface Coating;System;Techniques;Technology;Testing;Time;Translations;Universities;Work;