Oxford announces 6 new licensing opportunities

26 Apr 2007 | News

6 Licensing Opportunities

News from ISIS Innovation

1. Plant Transformation Technology

2. Low Cost Linear Oil Free Compressors

3. Novel Approach to Cancer Treatment

4. Pentalene and Metal Pentalene Compounds

5. Cell Population Array Imager (CPAI)

6. High throughput surface tension measurement

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1. Plant Transformation Technology

Research in Oxford’s Department of Plant Sciences has identified a model system for evaluating plant genes and their function in a high throughput manner.

Marketing Opportunity

Elucidating the function of the thousands of different genes in plant species is essential in developing new commercially important plants. High throughput screening methods in model species such as Arabidopsis have been widely utilised because of the efficient transformation methods available. However, Arabidopsis is not closely related to any crop species and developmentally important genes have distinct functions in different species.

Understanding how species-specific changes in gene activity alter agronomically important attributes of plant development will be an essential aspect of crop biotechnology.

The Oxford Invention

The Oxford invention describes a high throughput model system that allows generation of novel information regarding gene function utilising an Arabidopsis relative, Cardamine hirsuta. Although related to Arabidopsis, C.hirsuta has different developmental attributes as illustrated by the difference in leaf shape (shown below), which is controlled by differences in KNOX gene expression.

As well as being a novel platform for studying plant gene function, the Cardamine group of plants is more closely related to the commercially important Brassicas. This means C.hirsuta would be a useful model system for evaluating transgenic lines for adverse effects.

Patent Status

This work is the subject of patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents. Please contact the Isis Project Manager to discuss this further. Request Further Information: Project Number 960 Plant Transformation Technology.

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2. Low Cost Linear Oil Free Compressors

Oxford’s linear oil-free compressors are cost effective for non-space applications

There were two over-riding criteria in Oxford’s work to develop linear oil-free compressors for small cryocoolers for space applications; the compressor must be:

  • oil free, and
  • have a working life of at least 10 years.

The elimination of any contacting surface that can wear is this technology’s key feature, and this has been so successful that it is now the basis of almost all cryocoolers used in space; this technology has now been licensed to major aerospace companies.

During operation a linear motor drives a piston/cylinder system, and with precise assembly the piston moves within the cylinder without contact.  Typically the clearance between the piston and cylinder is held at less than ten millionths of a metre allowing compressor pressure differences of approximately 10 bar without power loss.  Provided cleanliness in the system is maintained; suitable materials for construction have been selected; there are no wear or failure mechanisms; this type of compressor can have a life exceeding the 10 year criterion.

Marketing Opportunity

These early designs were too costly for most commercial applications, but recent developments at Oxford have changed this situation.  We can now design oil-free compressors that have major advantages over conventional designs, and yet have the potential for low cost manufacture.

Applications for this new generation of linear oil-free compressors include those involving hazardous gases or those that require high levels of cleanliness.  A comparison of the existing compressor technology and the new linear technology will illustrate this.

In a traditional diaphragm compressor a piston generates a fluctuating pressure in a volume of hydraulic fluid.  A diaphragm separates the fluid from the gas to be compressed, and changes in hydraulic pressure deflect the diaphragm which in turn compresses or expands the gas volume.

Although diaphragm compressors can be used to compress virtually any gas to very high pressures there are some serious disadvantages:

  • Diaphragms have a limited life, and typically have to be replaced at intervals of ~ 5000 hours depending on the service, and as a consequence frequent maintenance is essential.
  • Diaphragms can fail prematurely, and a leak detection system is essential.
  • The diaphragm compressor is limited to small strokes with low speed operation. This tends to make diaphragm compressors large and heavy for the duty performed.
  • They are relatively expensive machines to manufacture and operate.
In a linear compressor the linear movement of the piston within the cylinder compresses and expands the gas in the compression volume to produce a pressure variation.  The motor stator complete with windings of the motor is entirely outside the pressure vessel, and the moving magnet inside the pressure vessel is readily contained in an hermetically sealed unit.  No oil is used anywhere in the operation of the compressor.  A module controls the dynamics of the assembly.  There are three advantages offered by this Linear Compressor Technology:
  • The significant reduction or even total elimination of maintenance requirements.
  • The elimination of any dynamic seals; no failure mode corresponds to diaphragm failure.
  • The complete elimination of oil from the compressor environment.

The Oxford Invention

Oxford has much experience in the design, manufacture and assembly of linear compressors, and has significant in house “know-how”. Patents and applications cover:

  • Linear motor designs that allow the stator assembly to be mounted outside the pressure vessel and which also offer high efficiency and low cost.
  • Designs for devices for controlling mean piston position and motor dynamics
  • Software for determining compressor operating parameters e.g. stroke and mean piston position from input voltage and current.  This avoids any requirement for position transducers to be mounted with the pressure vessel.

The new design of linear motor addresses issues for low cost, large scale manufacture:

  • Low moving mass
  • More efficient use of magnetic material – cost reduction
  • Simpler construction – lower cost manufacture
  • Design is readily integrated with existing linear clearance seal technology
  • Elimination of flexible current leads – simplifies the design and improves the reliability

Patent Status                                         

This work is the subject of granted patents and patent applications, and Isis would like to talk to companies interested in developing this opportunity. Please contact the Isis Project Manager to discuss further. Request Further Information: Project Number 917, 1055, 1557

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3. Novel Approach to Cancer Treatment

Work in the Cancer Research UK Laboratories at the Weatherall Institute of Molecular Medicine, Oxford, has uncovered an exciting new anti-cancer approach that has potential as a stand-alone therapy, and as a means of enhancing sensitivity to conventional anti-cancer treatments

Marketing Opportunity

One effective strategy to treat metastatic cancer is to induce sequence-specific silencing of target gene expression in cancer cells. The use of small interfering RNAs (siRNA) as gene silencing agents in mammalian cells is the most potent method. One important gene target with therapeutic potential in the fight against cancer is the type-1 insulin-like growth factor receptor (IGF1R). IGF1R activation induces tumour cell growth and protection from apoptosis, including that induced by conventional anti-cancer treatments. Its upregulation in tumours relative to normal tissues renders IGF1R a highly attractive anti-cancer treatment target. 

The Oxford Invention

The problem associated with IGF1R targeting is the high degree of homology between the IGF1R and the insulin receptor (IR). Because of this close homology, IGF1R kinase inhibitors and blocking antibodies can influence the function or cell surface expression of the insulin receptor, potentially inducing glucose intolerance and diabetes. The Oxford inventors used a scanning oligonucleotide array technology to design siRNAs that interact with IGF1R but not IR mRNA. This strategy has enabled identification of siRNAs that cause profound sequence-specific IGF1R gene silencing without affecting expression of the IR.

Commercialisation Opportunity

The IGF1R siRNAs have been tested successfully in vitro. Treatment of tumour cells with siRNAs blocks IGF signalling, inhibits cell survival and enhances sensitivity to cytotoxic drugs and irradiation. Work by the researchers has also shown that tumour cells remain sensitive to IGF1R gene silencing despite the presence of compensatory signaling via other growth factor receptors, or of downstream mutations causing constitutive activation of growth and survival signaling pathways. Following chemical modification to enhance stability and pharmacokinetic characteristics, the in vivo efficacy of these agents is currently being tested in human tumour xenografts.

These agents represent an exciting new anti-cancer treatment with wide applicability for patients with a variety of metastatic tumours.

Patent Status

This work is the subject of a patent application, and Isis would like to talk to companies interested in developing this approach for preclinical and clinical evaluation. Please contact the Isis Project Manager to discuss this further.

Request Further Information: Project Number 1206 Commercial Opportunity in Anti-Cancer Treatment

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4. Pentalene and Metal Pentalene Compounds

Isis Innovation, the technology transfer company of the University of Oxford, releases the synthesis of a versatile range of organic ligands that can be used to make a diverse array of multi-functional metal catalysts.

The cyclopentadienyl (Cp) ligand has remained the prevalent moiety in organometallic chemistry and homogeneous catalysis since the 1960s. Complexes of the permethylated derivative (Cp*) showed huge improvement in stability, solubility and crystallisability; leading to catalysts capable of operating over wider temperature ranges and at higher solution loadings thus substantially increasing process activity.

The Oxford Invention

Catalysts based on the pentalene (Pn) ring system (a ‘double-Cp’ equivalent) are hitherto unknown (Figure 1). Oxford scientists have overcome synthetic difficulties and now propose a rational, solution-phase route to substituted Pn ligands and their complexes.

Comemrcialisation Opportunity

This technology offers an opportunity to secure a foothold in an exciting, expanding field.  Pn complexes show a plethora of new binding modes and facilitate kinetically unfavourable chemical transformations such as C-C & C-H bond formation, N2 reduction to NH3 and hydrogenations.  Additionally, the Pn skeleton provides a platform to bind two or more metals (Figure 2) in complexes that are expected to display catalytic properties unavailable to mononuclear systems.  Furthermore, this chemistry leads to the possibility of novel advanced materials such as organometallic polymers with unique electrical and magnetic properties.

Patent Status

This work is the subject of patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents. Please contact the Isis Project Manager to discuss this further.

Request Further Information: Project Number 2475 - Pentalenes

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5. Cell Population Array Imager (CPAI)

Researchers at the University of Oxford have invented a cost-effective, portable and powerful Cell Population Array Imager.

The Oxford Invention

The CPAI is a specialised simple microscope which measures weak light signals over minutes to hours.  The signals come from individual live cells introduced into it as a suspension, such as blood cells.  Fluorescent or luminescent reporter molecules are pre-incorporated into the cells by well-established methods.  The heart of the CPAI is an imaging optical fibre-bundle forming a close-packed array of ultramicrowells imaged by a sensitive digital camera.  Each well accommodates just one cell.  Images of thousands of cells are acquired every few seconds. The fibre-bundle is in a closed flow-chamber so that cells can react with substances micro-pumped through it in solution.  Some of the cells may brighten transiently, with characteristic patterns.  For instance T lymphocytes react to anti-receptor antibodies that stimulate calcium oscillations.  For a few tens of minutes some of the cells wink like lighthouses, displaying a range of time-variant patterns.  Proprietary neural-network-based pattern-recognition algorithms running on an ordinary laptop computer then automate the classification of the winks into characteristic cell subpopulations.  For the first time we can classify cells into subsets primarily according to their biochemical function, not by molecular marker. This CPAI is an inexpensive and portable research instrument, in comparison with conventional flow cytometers or fluorescence microscope.  It is likely to improve “’omic” strategies by screening large tethered arrays of protein or RNA ligands, and also has the potential to be developed as a field-portable cytometer with primary healthcare and third-world applications.

Solutions provided by this invention

The CPAI solves all the limitations that afflict two related technologies:

1. Conventional video-imaging by fluorescence microscope to record signals from cell populations is constrained by:

  • limited number of cells analysed, so subset-typical patterns aren’t identifiable
  • cells being displaced by reagent passage during image acquisition, so data are lost
  • cumbersome and expensive equipment
  • requirement for relatively large cell numbers

2. Flow cytometers, when used for time-varying functional studies, assume each cell behaves identically to all the others in the sample. They measure only the average of the whole poputaion; so individual differences are hidden.

Patent 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.

Request Further Information: Project Number 1547 Cell Poputaion Array Imager (CPAI)

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6. High throughput surface tension measurement

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.

Request Further Information: Project Number 2538 High throughput surface tension measurement.

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