University of Cape Town

Hysteroscopy is a procedure that requires the direct visualization of the uterine cavity to diagnose and treat abnormal uterine conditions. Health professionals regard it as the gold‑ standard for diagnosis because of its effectiveness and efficiency.

Traditional hysteroscopy systems, and the equipment required for its use, can be expensive and inaccessible for Global Health needs. Furthermore, these systems employ rigid hysteroscope tips that can cause patient discomfort, often leading to the need for general anesthesia. This in turn limits the procedures to the operating theatre and adds to waiting time delays.

These limitations coupled with bulky and fragile equipment result in an immobile system only available in a tertiary healthcare facility, requiring highly skilled professionals.

Market trends also favour minimally invasive devices that enhance the patient experience and enable the broader use of technology other than traditional users.

The University of Cape Town’s solution is a reusable mobile hysteroscopy system for application at the point of care. The University’s Medical Devices Laboratory has worked with some of the best gynaecologists in South Africa to understand their challenges and to co‑design the solution with their constraints in mind.

The result is the FlexiGyn device which provides for single‑handed operation and its ease of use broadens the scope for health professionals, including nurses, who could operate it.

FlexiGyn is a system that consists of a handheld control base and a flexible rod. A built-in CMOS camera and LED light source are located at the distal end of the flexible rod. The flexible rod can bend up to 180° in 4 directions through user-controlled input via its novel smart bending system which is powered by a rechargeable battery. The result is a system with controlled flexibility that ensures maximum patient comfort.

The system integrates with a smartphone or a tablet for visualization, which also enables the user to save any videos or images.

A final part of the system is a sterile disposable sheath that covers the flexible rod and isolates it from patient contact, eliminating the need for intensive sterilization after use. The sheath also has two working channels, one for distention media and the other for the insertion of operative instruments. A significant benefit of the device is its application both inside and outside of the operating theatre without the need for general anesthesia. This is made possible through the device’s small diameter and inherent flexibility.

The system also offers incredible mobility because of its single‑handed operation, is operated from the battery. It has a built-in camera and light source and integrates with a smartphone or tablet.

The primary area of application is in the female genital tract.

Potential users include gynaecologists, senior nurses and urologists.

The technology that encompasses the highly flexible rod could however be translated to other gastro‑intestinal scopes and other endoscopic devices.

Our invention consists of an array of Inertial Measurement Unit (IMU) sensors that are synchronized with one another. The IMU sensors measure the inertia and position of the subject within a space. The IMUs’ output is their collective measurement of inertia and forces, generating big data. The data serves as input into a personalized kinematic model for the test subject. The kinematic model can estimate the Ground Reaction Forces (GRFs) and a torque profile of the test subject around a specific sensor or in relation to one another.

There is no limit to the number of sensors that can be used on a test subject or on multiple test subjects of locations.

Our sensors are 5 centimeters in diameter, 10 millimeters thick and independently powered. The sensors synchronize with one another wirelessly, and the user can use as many as needed on the test subject‑ animate or inanimate.

Currently, motion tracking systems are either based on Optical Systems to capture and analyse movement or use sensors such as Inertial Measurement Units (IMUs).

Optical systems employ several cameras to capture images of the moving body of interest. From these images, kinematic models may be built that gives insight into the movement of the object. These systems are typically very accurate but are expensive and tracking can only occur within the facility where the cameras are installed. An example of an optical system is the Vicon motion capture system.

IMU systems, on the other hand, include sensors which are placed on the body parts of interest. These sensors measure the inertia of the moving parts from which kinetic models can be developed. IMU systems are potentially cheaper and more portable than optical systems and do not limit the study subject to a specially-fitted facility, but they are less accurate than optical systems and time synchronization with multiple sensors is difficult.

The trend in the “biomechanics market” in movement and sports sensors is the use of AI (machine learning and neural networks) to diagnose the performance of athletes and train them using the information generated. The quality of the AI-trained database depends on the data points required to improve accuracy.

The nucleus of a cell is central to the well-being of any living organism. It stores and organises information from other cellular components and protects this information. It communicates with the rest of the cell, exchanges RNA and facilitates several important processes.

The nuclear envelope is a double membrane surrounding the nucleus and contains pores forming part of a large complex of proteins known as the Nuclear Pore Complex (NPC). Any material entering or exiting the nucleus must pass through the NPC. 

Nuclear transport proteins (NTPs) are proteins that assist with the transport (import or export) of large molecules, such as RNA, across the nuclear membranes of cells and through the NPC. Examples of nuclear transport proteins are Karyopherins. Various studies have shown that the Karyopherins and other NTPs are implicated in the proliferation of various cancer types. 

Early research at UCT by Prof Virna Leaner and Dr Pauline van der Watt showed that Crm1 and Karyopherin β1 (Kpnβ1), also known as Importin β, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.[1] Others have also identified that some nuclear transport proteins are elevated in various cancer cell types. However, the inventors were the first to have identified a signature of nuclear transport proteins in the serum of patients that is indicative of cancer versus no-cancer.

More specifically, the inventors have identified a total of 7 nuclear transport proteins (Kpnβ1, CRM1, Kpnα2, CAS, Ran, Ipo5 and Tnpo1) that are secreted by cancer cells as a family and detectable in serum. These 7 proteins, identified following a screening process of about 26 related NTPs, together provide exceptional predictive ability for non-specifically detecting cancer, even early-stage cancer. The results are highly promising and patent applications haven filed. This indicates strong potential utility as a cancer diagnostic.

The ability to discriminate between cancer and no-cancer was evaluated for different combinations of the seven proteins, including each one individually. As an example, the combination of all seven candidate biomarkers gave an Area-under-Curve (AUC) of 0.944 with a sensitivity of 92.5 % at 86.8 % specificity, which is exceptional ability to discriminate between cervical cancer cases and non-cancer controls. The same combination gave an AUC of 0.963 with a sensitivity of 95.3 % at 87.5% specificity, which indicates exceptional ability to discriminate between oesophageal cancer cases and non-cancer controls. 

[1] P.J. van der Watt, C.P. Maske, D.T. Hendricks, M.I. Parker, L. Denny, D. Govender, M.J. Birrer, V.D. Leaner, “The karyopherin proteins, Crm1 and karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation”, Int. J. Cancer 124 (2009) 1829–1840. https://cansa.org.za/files/2012/05/Karyopherin-proteins-Crm1-and-Karyopherin-b1.pdf).

The main benefit is the potential ability to non‑specifically detect cancer, even early-stage cancer, through a simple blood test. This will ensure patients are put on anti‑cancer treatment earlier, which will reduce the total cost of treatment and increase the survival rate. The technology can also potentially be used to track the efficacy of anti‑cancer treatment, and therefore serve as a companion diagnostic to anti‑cancer therapies. 

• A blood‑based early‑stage cancer diagnostic.
• Prognosis tracker for cancer therapeutics.
• Companion diagnostic alongside cancer therapeutics such as nuclear transport protein inhibitors.

UCT is looking for a partner to further test this technology and develop this into a commercial diagnostic test through regulatory approvals. The ideal commercialisation modality is a license.

• PCT patent application number PCT/IB2021/061690
• UK patent application number 2019682.0

Background

Various cancers, including gynecological cancers, are becoming resistant or insensitive to platinum-based chemotherapy and consequently higher dosages are required to be effective. Unfortunately, most of these chemotherapeutic drugs cause undesirable systemic effects such as cardiac or renal toxicity, alopecia, marrow aplasia, nausea, and vomiting. There is thus a critical need for new therapies or combination therapies with superior anti‑cancer effects, yet with fewer side effects and lower cancer resistance.

The inventors have previously demonstrated that specific small molecule inhibitors of the nuclear transport protein Karyopherin Beta (β) 1 have superior cell-killing effects to Platinum-based chemo at reduced toxicity (i.e., no toxicity on non-cancer cells, targeting only the cancer cells). UCT in conjunction with the University of Louisville have filed patents for the anti-cancer therapy. The lead molecule is codenamed INI‑43 or C43 (a quinoxaline‑based derivative).

The inventors have further investigated the potential of INI‑43 to be used in conjunction with other anti‑cancer drugs as an anti‑cancer combination therapy. A new technology flowing from this work is what is described in this advertisement, and has also been patented.

Technology Overview

The technology is an anti‑cancer combination therapy consisting of an effective dose of a small molecule inhibitor of nuclear transport protein Karyopherin Beta (β) 1 as previously patented and a effective dose of any Platinum-based chemotherapy. In vitro data generated by UCT showed that the combination of INI‑43 and Cisplatin leads to selective cell death at significantly higher rates than predicted in cervical and oesophageal cancer models. The combination shows clear synergism in that the combined cancer‑killing effect is significantly higher than what can be expected if one considers the known cell‑killing abilities of each drug separately. This combination therapy thus holds great promise for providing effective chemo at reduced toxicity and with lower side effects. The next stage of the development includes in vivo activity and ADMET tests, dosage determination, clinical trials and regulatory approvals.

Benefits

The main benefit is that the combination therapy potentially allows for patients to be treated with lower dosages of Cisplatin or other Platin‑based chemo, reducing the overall toxicity, but maintaining the same or superior anti‑cancer effect due to the synergistic effect between Cisplatin and INI‑43. INI‑43 on its own has been shown to have lower toxicity than Cisplatin (no toxicity on non‑cancer cells). Cisplatin on the other hand does not differentiate between cancer and non‑cancer cells, which results in adverse side effects and long‑term complications.

Applications

In applications where advanced‑stage cancer requires very high dosages of Cisplatin to be effective, the new combination therapy could potentially be used to alleviate side effects by reducing Cisplatin dose.

Opportunity

UCT is looking for development partners to assist with pre‑clinical and clinical trials as well as regulatory requirements and potentially a licensing partner for the commercialisation of the combination therapy. A commercialisation strategy has not yet been formulated.

Please also see PCT patent application number PCT/IB2021/057054.

Immortalized cell lines have been used extensively in cancer biology and as a model system to test the efficacy of vaccines, but their use is becoming increasingly limited because of extensive genetic and phenotypic variations compared to those expressed in cancer patients. 

Similarly, cancer cell lines have been used as research tools but unfortunately, these cells also suffer some of the shortcomings presented by immortalized cells, as they express antigens that are often different from those expressed on the tumours of individual patients.

Based on available information, there is no in vitro method that allows isolation from cancer patients and propagation of primary cancer tumor cells for long term growth in culture. 

The current invention was conceived in response to the limitations associated with using immortalized cell lines and cancer cell lines when testing potential drugs. 

In short, the invention is an in vitro method to obtain (isolate) and propagate (culture) primary tumor cells from human tissue samples (biopsies). A kit containing growth factors, supplements, and steroids is being developed to be commercialized. The constituents of the kit allow extraction and maintaining of the cells for longer periods of time. 

The method has been tested and proven in various cancer types, including lung, kidney, pancreas, and breast cancers. 

The main benefit is that the method overcomes the challenges associated with the use of immortalized and cancer cell lines, i.e., the genetic and phenotypic variations are not present because cells are directly cultured from live cancer patient tissue samples. This could potentially improve the efficacy of drug targets in drug discovery programs.

• Drug Discovery: research institutions, companies, or organizations conducting drug discovery that require cell lines for testing drugs that are similar to tumor cells from real cancer patient samples (biopsies).
• Cancer Research: research institutions, companies or organizations conducting research into the mechanisms and characteristics of various cancers
• The invention can also be used as a therapeutic adjunct or a monitoring tool whereby the autologous tumor cells from patients could be kept alive, and immune cells from the blood could be retested on these cell cultures over a period of about four or five months down the line to see whether there is a tumor residual effect. 

UCT is looking for partner(s) interested in either:

1. Adopting the method for internal purposes, drug discovery or cancer research, and/or,

2. Developing a ready‑for‑sale kit incorporating the cell culturing components and instructions to perform the method; marketing, selling and/or distributing the final product to customers.

We anticipate that the kit can be marketed on existing online platforms selling research reagents or tools. UCT already has an existing partnership with such online platform.

• UK Patent GB2572914B (granted)
• USA Patent Application No. 16/479,202
• UK Patent Application No. 2210579.5 (divisional)
• South African patent application 2019/04830

A Magnetic Resonance Imaging (MRI) scanner applies magnetic fields to a human or animal in order to generate an image of a specific region of the body. Due to a number of internal and external effects, these fields are never completely homogeneous. Distortion of the magnetic fields may lead to defective images which could potentially lead to false diagnoses. Also, during the course of an MRI scan, there is typically a level of magnetic drift which reduces the image quality, particularly during long scans.

It is therefore important to estimate and correct for inhomogeneity in the magnetic field. Modern scanners adjust for this through a process called shimming. The shim correction device in most MRI scanners includes a number of coils that produce small magnetic fields which are superimposed on the main magnetic field. Shimming of the magnetic field is typically performed once before the scan sequence begins. However, during a long scanning period, the initial shim prepared by the scanner could be compromised, rendering the final MRI images inaccurate.

This innovation is in the form of software that runs on an MRI machine which estimates and corrects for main magnetic field drift by using a double volumetric sequencer navigator to measure and adjust shim over selected regions in a “slab-by-slab” fashion. 

A 3D navigator pulse is interleaved in the scanning sequence after the acquisition of each volume. A second navigator is introduced, with a different echo time to the first, before the next volume is acquired. The two corresponding navigator images are obtained and a magnetic field map is determined via complex division of the images. This magnetic field map is then used to determine the parameters required to adjust the system central frequency of the MRI scanner to compensate for drift.

The method ultimately improves the quality of images produced by imaging scanners such as MRI’s. 

The technology has been jointly developed by the University of Cape Town and the Massachusetts General Hospital (MGH) in the United States. The patents are co‑owned.

• No hardware requirement ‑ innovation is simply uploaded as software onto existing MRI shim correction devices / integrated into the pulse sequence
• Useful particularly to smaller, cheaper MRI scanners where cheaper magnetic coils are used, or applications where "software tricks" allow for cost advantage over competitors
• Measure, report, and correct for all changes in the magnetic field throughout an MRI scan
• Improved image quality
• Ability of the double volumetric navigator sequence to measure and adjust shim over selected regions in a ‘slab-by-slab’ or ‘slice-by-slice’ fashion
• Integratable into any MRI pulse sequence, including functional MRI (fMRI) and diffusion tensor imaging (DTI)
• Higher order shims can be implemented if the hardware of the particular MRI scanner permits this

Hospitals, medical practices, MRI instrument manufacturers and veterinary practices that require accurate images in order to investigate the anatomy or physiology of a human or animal body.

Applicable particularly to smaller, cheaper MRI scanners where cheaper magnetic coils are used, or applications where "software tricks" allow for cost advantage over competitors 

UCT and MGH are looking for a licensee. 

• US Patent 10,018,700 (granted)
• South African Patent: 2015/04963 (granted)

Background:

Biomedical studies (e.g., prosthetic development and injury rehabilitation), sports science research, high-performance optimization research and assessments, and bipedal or quadraped movement measurement often require accurate measurement of the forces exerted by the subject being studied (typically Ground Reaction Forces or GRFs). These forces are useful indicators of a person’s balance, gait, and exercise performance.

3-dimensional (3D) force measurements can measure the force vector but are typically prohibitively expensive (>US$ 50,000). Low-cost force plates exist, but these plates have not been designed for robust sports biomechanics applications and are problematic because they measure only vertical (not horizontal) forces and typically cannot accurately measure force in 3D.

Furthermore, the use of existing force plates is constrained by the testing protocol and location. Subjects need to step exactly on the plate (usually 500mm x 500mm in area), which can cause unnatural motion if they are running or doing a dynamic movement. This constraint increases testing time as subjects need to adjust their gait for the test. This may in turn result in early fatigue, which further increases testing duration. Using more than two force plates simultaneously (i.e., an array) allows for more natural movement of the subject being studied, thus more accurate determination of GRFs, but in practice it is rare due to high cost.

Overview of Invention:

The UCT force plate is an instrument that measures GRFs while the person being measured is standing, performing exercises on, or moving across the plate. The design and manufacture of the UCT force plates enable the accurate estimation of the full 3D GRF‑vector with the aid of sophisticated Machine Learning models without the need for expensive, multi‑axial load cells with strain gages.

The design and configuration of the force plates enable the user to use them as a dual plate or in an array. UCT inventors have also designed the force plates such that the array 4x4, 8x8 and 10x10 arrays could be a fraction of the cost of an equivalent dual or single plate arrays.

Benefits:

The benefit of the array configuration is that it enables the test subject greater freedom‑of‑movement than achievable using a single force plate with limited testing surface area. This will improve the accuracy of measurements and outputs, enabling the user or researcher to build information‑rich models of movement and assessment. The unique selling position for the force plate is to enable the measurement of more natural movement and using that to improve performance and recovery at a reasonable cost.

The combination of components, design, and software algorithms collectively contribute to the cost advantage that we will potentially have in the market relative to the competitors. The cost advantage will reciprocally be valuable to build arrays of the force plates to cover larger capture-surface areas, which will increase the fidelity of the data capture.

Furthermore, the force plates are mobile, will interface with a mobile application and can be used in research and teaching and learning environments too.

Applications:

The potential users of the force plate could include researchers involved in tracking locomotion for orthopedics and prosthetics, sport science, aerospace and robotics. Other users could be biomechanics consultants, bio-kineticists and sports scientists focused on tracking athlete performance and athlete or patient recovery from injury. There is also the potential for the technology to be used in animal health and sports, such as performance testing of racing horses.

Another potential application is neuromuscular rehab for victims of strokes and spinal cord injuries and any other industry where having numerical metrics to describe a subject’s movement is useful.

The force plates could be used with OptiTrack or Vicon motion capture systems.

Opportunity

The technology is currently being developed by a UCT spin‑off company.

UCT is looking for companies that would like to partner with its spinoff company and/or purchase the dual or array system from them.

It will also be possible to use the force plates to validate new use cases in collaboration with the spin‑off company.

Patents:

Granted Priority Founding Patent number GB2589138

International Patent Application PCT/IB2020/060685

Australian Patent Application No. 2020386666

South African Patent Application No. 2022/05393

United States of America Patent Application No. 17/756,230

European Patent Convention Application No. 20811740.8