Summary:

Program Description

New technologies that allow for implementation of flow cytometry analysis for introduction into resource-poor settings.

A call for proposals is being launched in the framework of the Global Enterprise R&D Collaboration Agreement between the Israel Innovation Authority and BD. BD is a large medical device company with a global presence serving healthcare needs around the world, in both high- and low- resource settings.

BD is making high speed cell sorters and cell analyzers for use in both research and healthcare settings. Key to these technologies is the ability to move cells in suspension quickly through the detection area and the ability to generate and detect light from these cells. Scattered and emitted light is analyzed to determine the presence of endogenous fluorophores or to detect specific surface proteins that have been chemically labeled. These technologies have been broadly adopted and have found uses in areas ranging from oceanography to immunology to the treatment of Type II diabetes. BD is seeking technologies that allow for inexpensive implementation of flow cytometry analysis for introduction into resource poor settings. BD isfocusing on three areas for cost reduction: flow-induced entrainment of suspended particles, excitation of endogenous or introduced fluorophores and detection of fluorescent and scattered light.

1. Flow
   The flow subsystem’s primary role is to hydrodynamically focus, orient and position particles of interest such that they can be individually characterized. Current embodiments use hydrodynamically focused systems with a clear carrier fluid. We are seeking novel flow system concepts which can more cost effectively or efficiently accomplish similar outcomes. The ideal solution should:
   • handle particles of interest that are between 1 and 20 microns in diameter
   • position the particles accurately, reliably and individually in the excitation/detection path.
     The new flow system needs to present up to 30,000 particles per second for inspection.
2. Excitation
   The excitation subsystem’s primary role is to excite fluorophores on the particles of interest. Current embodiments use lasers, or diodes. We are seeking novel means for individually exciting fluorophores on the particle of interest. The ideal solution should be capable of operating in wavelengths between 350– 850 nm in current systems.
3. Detection
   We are interested in new methods for measuring the light that is scattered from or emitted by the particles of interest. Current embodiments use prohibitively expensive photomultiplier tubes. The detection system must be able to collect and quantify the optical characteristics of the particles of interest at the speeds mentioned above. The detection system should be able to measure light in the visible as well as the infrared (400-950 nm).

For more information on BD’s flow cytometry, please see at the technological annex to this call (p. 3).

The proposals will be evaluated based on the ability of each platform to reduce the cost of existing flow sub-systems while retaining key performance characteristics. Each proposal will additionally be evaluated based on technical feasibility, manufacturability and integration potential into a complete flow system.

For more information on BD activities, please visit the corporate website at: www.bd.com

Companies that are interested in applying should send a summary proposal to: adam.zerda@bd.com and tim.petersen@bd.com
with a copy to Noam.BarGal@innovationisrael.org.il

Proposals will be evaluated by the Innovation Authority and BD.Companies whose proposals are found suitable will be invited to submit requests for support within the Innovation Authority’s Framework for R&D Cooperation with Multinational Corporations. Approved applications will receive the following assistance:

• An Innovation Authority Grant of up to 50% of the project’s approved budget;
• Additional assistance from BD of the same budget amount in-kind, for support in the technological and regulatory areas; use of laboratory equipment for R&D; sub-contractors and professional consultants; etc.

Technological Annex 
The technology underpinning of BD’s product offerings, flow cytometry, is playing a crucial role in furthering advances in molecular and cell biology. Flow cytometry is an advanced technology for counting, examining, and sorting individual cells. Equally important to this advance was the parallel discovery and development of monoclonal antibodies that allowed researchers to detect and label specific cell populations with fluorescent antibodies.

Flow Cytometry 
Flow cytometry offers three important capabilities to researchers and clinicians. First, flow cytometry analyzes a population of cells on a cell-by-cell basis, a critical capability for today’s researchers and clinicians who are looking for the very few cells among the many cells in a sample (often like needles in a haystack) that will enable them to study a disease state or biological process. Second, flow cytometry is extraordinarily rapid. Routine sample analysis rates can range up to 10,000 cells per second—an incredible advance over historical methods of visually examining and counting cells. Finally, flow cytometry has the capacity to simultaneously measure multiple parameters (multiplexing) of single cells. Multiplexing allows researchers and clinicians to gather more information from a single sample faster than ever before. These capabilities have made flow cytometry a powerful tool with multiple applications for researchers and clinicians alike.

How Flow Cytometry Works 
Flow cytometers contain three main systems—the fluidics, the optics, and the electronics. The fluidics system funnels a sample of cells (for example, a sample of human blood) into a single stream so that the cells pass one at a time through a laser beam. As each cell passes through the beam, it scatters light and may emit fluorescent light. These light signals are collected by the optics system and routed to various detectors. The signals received by the detectors then are converted into numerical values by the electronics system. Results can be displayed on the screen or saved for future analysis using specially designed software. As each cell moves through the beam, its parameters (characteristics) are measured and recorded, along with the time that it passed through the beam. Typically data is collected for at least 10,000 cells per sample. The basic principle of how flow cytometers operate is shown above.