Brooks B.D.,Wasatch Microfluidics |
Brooks A.E.,University of Utah |
Brooks A.E.,North Dakota State University
Advanced Drug Delivery Reviews | Year: 2014
With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. © 2014 Elsevier B.V.
Brooks B.D.,Wasatch Microfluidics
Current Drug Discovery Technologies | Year: 2014
The pharmaceutical industry is experiencing comeback sales growth due in large part to the industry's R&D efforts that center on biologics drug development. To facilitate that effort, tools are being developed for more effective biologic drug development. At the forefront of this effort is epitope characterization, in particular epitope binning, primarily due to the role an epitope plays in drug function. Here we detail the financial advantages of epitope binning including (1) increased R&D productivity due to increased work in process, (2) reduced number of "dead-end"candidates, and (3) increasedability to reengineer antibodies based on the epitope. With the arrival of high throughput biosensors, this manuscript serves as a call to push epitope binning earlier in the biological drug discovery process. © 2014 Bentham Science Publishers.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 329.75K | Year: 2014
DESCRIPTION (provided by applicant): Real-time label-free technologies such as surface plasmon resonance biosensors provide high-resolution information about the kinetics, affinity, stoichiometry, activity, and specificity, of two (or more) binding partners. While the application f biosensors is well established, current instrumentation has limited sampling throughput. Screens of even a fairly small chemical library (e.g., 3000-5000 compounds) require days to weeks to complete using traditional label-free instruments. Because of the quality of the data generated by SPR, drug discovery scientists are clamoring to use enhanced biosensors as a screening tool for small molecule applications; however, lack of throughput hinders their ability to move in this direction. We propose to develop a biosensor platform that has increased throughput yet maintains the data quality and ease of use to which researchers are accustomed. We will couple our novel Continuous Flow Microspotter (CFM) with an enhanced-sensitivity SPR
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.02M | Year: 2015
DESCRIPTION provided by applicant Real time label free technologies such as surface plasmon resonance biosensors provide high resolution information about the kinetics affinity stoichiometry activity and specificity of two or more binding partners While the application f biosensors is well established current instrumentation has limited sampling throughput Screens of even a fairly small chemical library e g compounds require days to weeks to complete using traditional label free instruments Because of the quality of the data generated by SPR drug discovery scientists are clamoring to use enhanced biosensors as a screening tool for small molecule applications however lack of throughput hinders their ability to move in this direction We propose to develop a biosensor platform that has increased throughput yet maintains the data quality and ease of use to which researchers are accustomed We will couple our novel Continuous Flow Microspotter CFM with an enhanced sensitivity SPR biosensor from BiOptix to enable label free screening and kinetic analsyis of small molecules and biologics In high throughput screening mode our channel integrated CFM E biosensor platform will be capable of collecting data for andgt samples in less than hours a sampling rate x faster than fastest small molecule capable label free biosensor the Biacore PUBLIC HEALTH RELEVANCE Label free real time biosensors enable the measurement of the kinetics of biomolecule binding Getting this information earlier in the drug discovery process reduces false positives identifies candidates that may have been missed improves subject matter for patent filings and increases the probability of the selected candidateandapos s eventual success Traditional label free biosensors have limited sample throughput which has restricted their use to secondary roles By combining our highly parallel microfluidic sample delivery technology with a small molecule sensitive biosensor we will enable the high throughput label free analysis of small molecules and biologics which offers significant potential for increasing the efficiency of early stage drug discovery
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 811.09K | Year: 2011
DESCRIPTION (provided by applicant): The goal of this Phase II STTR project is to develop a real-time label-free biosensor that can analyze 96 samples at a time, compared to the 6 samples possible with current technologies. This platform will initially bedemonstrated with G-protein-coupled receptors (GPCRs) and antibodies. What both applications have in common is the need for higher- throughput sensing, and demonstrating the integrated system for these will illustrate its versatility and potential contributions across the wide spectrum of biosensor applications. For the GPCR demonstration, our work with standard SPR instruments has shown that the choice of detergent(s) is critical for obtaining active solubilized receptor. However, standard low throughput SPR biosensors have two overwhelming drawbacks: (1) The analysis of 96 solubilization conditions requires more than two days and the receptor loses significant activity during this time, which makes it difficult to compare the results obtained at the beginning and end of the analysis and (2) the SPR instrument is limited to testing only one analysis buffer at a time, which means that the success of the entire assay depends on the initial choice of analysis buffer. In Phase I, we developed a 96-channel Continuous Flow Microspotter (CFM) printhead and demonstrated the ability to print GPCRs onto a sensor surface directly from crude media using up to 96 different analysis buffers. The GPCRs were also kept wetted and active throughout the printing process by theCFM's enclosed microchannel printing network. In the final experiment, we solubilized the GPCR CCR5 from whole cells using 192 different detergent conditions and spotted them onto an SPR sensor surface using our CFM printhead. We then tested the activity of the receptor and used the ligand binding results to determine that a certain combination of detergents best enhanced receptor activity. To run this analysis with a standard Biacore technology (e.g. T100) would have required four days of instrument time.In comparison, we were able to perform the analysis in less than 2 hours. In Phase II, we propose to integrate the 96-channel CFM from Phase I with a commercial SPR imager to enable automated interaction analysis in a highly parallel format. The followingspecific aims detail the combination of Wasatch's microfluidic technologies with the commercial IBIS SPR imager to produce a high-throughput label-free biosensor. 1. Refine the 96-channel CFM printhead design from Phase I to enable optimal performance whenmounted on the IBIS SPR imager. 2. Mount the 96-channel CFM onto the IBIS SPR imager and optimize the fluidic parameters that affect platform sensitivity and uniformity. 3. Automate the CFM and SPR components within one seamless instrument: Automation ofthe flow cell positioning, sealing, fluid handling, valving, in-line degassing and temperature control. Integration of the CFM and SPR imager control software and data collection/analysis software. 4. Demonstrate use of the automated system with GPCRs andantibodies. PUBLIC HEALTH RELEVANCE: Antibody analyses are one of the most common applications of biosensor technology and are typically straightforward. GPCRs are the hottest and most challenging system that biosensor users are tackling. Up to halfof the drugs on the market today modulate some form of GPCR activity, and it is estimated that 25-50% of the total drug targets are in the GPCR families. GPCRs are the most studied of the major drug target classes, yet they are challenging to work with because they are normally membrane associated, present in low abundance, and unstable. By enabling the high throughput study of GPCRs, there is enormous potential for speeding drug development, treatments, and the associated health of patients with hundredsof different diseases.