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Technology Transfer from the University of Oxford

High throughput surface tension measurement - Isis Project No 2538

Researchers at the University of Oxford have invented a novel measurement for high throughput screening to prevent false negatives in drug discovery.

Marketing Opportunity

High throughput screening in pharmaceutical drug discovery (prevention of false negatives)

Process control in manufacturing surface active products (inks, detergent products, agrochemicals)

Quality control in production lines

Screening tool for microfluidics compatibility (lab-on-a-chip samples)

Multiplexing multiwell assays using combined ELISA and enzyme-linked immunosurfactant assay (ELISURFA)

The Oxford Invention

The invention offers a rapid method for the measurement of surface tension at a fluid-gas (or fluid-fluid) interface in multi-well plates, based upon computer-generated repetitive high contrast patterns imaged through the samples using a CCD camera controlled by dedicated image analysis software.  Rapid well-by-well feedback control of the optimal spatial frequency of the analytical pattern ensures the widest possible measurement range (by keeping the signal in the image within the most accurate linear range despite wide variation due to different lensing effects).  

Applications

A dedicated stand-alone instrument offers very high throughput with minimum constraint on sample size and composition, except for the requirement that the sample be at least translucent at a wavelength between 400-900nm.  A reflection mode variant removes even this constraint.

A wide range of applications are envisaged; a subset are suggested in the marketing section above.

Advantages

Measurements are very rapid (96 wells read in parallel with a reading time of less than one second), use small samples (typically 50-200 microlitres), require no contact (so sterility is maintained and toxic aerosols are never created), and may be made at any temperature and in non-air atmosphere if required.  Furthermore, measurements may be made repeatedly such that reactions may be followed dynamically in real time, rather than being constrained to an end-point value.

The method is especially suitable for robotic plate handling systems and may be incorporated efficiently into the work flow of a high throughput screening assay.  This makes the method particularly relevant for screening HTS assays for unexpected surface tension changes (predominantly due to the library compounds that vary from well to well, but also able to detect bubbles and foreign bodies in wells) that might otherwise give rise to false negatives or false positives in the screen.

Application of a feedback between the image analysis software and the pattern generator is used to maximize the range of surface tension effects that can be measured.  This is achieved by feedback regulation of the spatial frequency of the pattern until a waveform with a wavelength in the linear range is detected in the image.

Patents Status

This work is the subject of a patent application. Interested parties are welcome to discuss with Isis Innovation on how to utilise this invention. Please contact the Isis Project Manager to discuss this further.

Figures

A digital demonstration of the dynamic measurement; a line scan or simple photodiode system could provide an analog voltage varying so that processing could remain in an analog frequency domain.



 

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