Public Funding for Active Needle Technology Ltd

This project aims to deliver a revolutionary new, low pain, low trauma tattooing system for the \>$2bn global tattooing market. It builds on a highly successful previous IUK grant which demonstrated proof of concept of ultrasonic low pain tattooing. The innovation is highly novel. There are no other tattoo machine based approaches to reducing pain and skin trauma. Some skin creams have been used, but are problematic for several reasons, particularly in the short term effectiveness, the potential for compromising the quality of the tattoo work and that the artist cannot 'prescribe' such materials. The benefits of low pain tattooing are an improved experience for the client, longer sitting times and therefore great efficiency for the artist and less unwanted movement (jerk response) in relation to pain. The device also offers low skin trauma. This effect allows for higher quality work as there is much less redness in the tattoo field. These effects are achieved through the ultrasonic motion of a needle - 1000ths of a mm and thousands of times per second, acting as a microscopic hammer action needle, parting the skin, lowering in skin friction and triggering fewer pain receptors. The key objectives are to optimise the performance of the ultrasonic low pain tattoo device, called TranQuill(r), to address the shortcomings of the prototype device in terms of: - vibration: which may result in vibration-related long term injury to the user. - optimisation of ultrasonic frequency and more importantly, amplitude. Too much vibration leads to undesirable results and too little will not have the beneficial effects of low pain tattooing demonstrated in the proof of concept phase. Industrial design to allow for a premium product with very high desirability. Collaborations with artists, established in the prototype phase, will be built upon to ensure a world leading product is produced in a market-ready state.

Although great progress has been made in the treatment of some common cancers there remain many indications where there has been little improvement in care over decades. The most difficult tumours tend to be inoperable with treatment options limited to chemotherapy and radiotherapy. Chemotherapy is administered systemically and a balance between toxicity and tumour dose is hard to achieve. Radiotherapy is more effective as it can be targeted to the tumour. However, it relies on the presence of oxygen to generate cell killing free radicals, meaning that aggressive oxygen deficient (hypoxic) tumours cannot be treated without unacceptable off-target toxicity. Recently, nanoparticles have begun use as radiosensitisers to enhance the efficacy of radiotherapy treatment. Direct intratumoural injection is currently under active investigation as a method of reducing systemic toxicity but presents a threefold challenge for clinicians. Firstly, direct real-time imaging of the needle tip into the tumour is difficult, particularly for deep tumours in, for example, the pancreas. Secondly, it is not known how far from the needle tip the active ingredient disperses into the tumour. Thirdly, conventional injection provides little control of the distribution of the nanoparticles within the tumour. Consequently, it is very difficult for the clinician to devise an effective clinical intervention strategy for intratumoural injection. This project brings together collaborators with broad and deep skills in the area of nanoparticle development, fluid delivery and medical imaging. This programme will develop the basis of a clinical intervention strategy for cancer treatment of human patients using intratumoural injection.

"Active Needle Technology Limited ""ANT"" are the developers of a novel ultrasound needle ""driver"" technology that exploits the properties of ultrasonic vibration to aid the passage of needles through the tissues of the body. Crucially, the ultrasonic vibration is proven to reduce the needle insertion force and tissue trauma. ANT have developed a medical biopsy needle that must be inserted deep into the body to collect tissue samples for medical tests. The ultrasonic vibration not only eases the passage of the needle into the body, but also has the added benefit of improving the accuracy of tissue sample collection (reducing the deflection of the needle). During development, ANT have noticed a numbing sensation of the active needle on the skin. In consultation with an expert in pain management, ANT believe the ultrasonic vibration interrupts nerve function in the skin therefore reduces the pain of the needle in the skin. Initial tests on un-optimised needles have shown that the effect is real. The business wishes urgently to evaluate the use of the active needle technology and leverage its expertise in ultrasonics to reduce the pain and trauma associated with tattooing. This enables the business to access a market with a potential value an order of magnitude larger that is order of magnitude larger than the medical biopsy market, but that is also important in reconstructive surgery, e.g. addition of a false nipple following post-surgical resection of the breast. This application enables ANT to: * Research and develop a functional prototype active needle enabled tattooing machine; * Conduct to key body of tests: 1. One: using human volunteers to determine if the machine is less painful that conventional tattooing methods; 2. Two: In consultation with tattooing artists, determine if the Active Needle tattooing machine is acceptable to tattooing artists. This project enables the applicant to access a huge global potential market that is estimated to be worth approximately $1.6 bn p.a. in the US alone. The innovation in this project: current tattooing machines operate at low frequencies (similar to the flicker rate of a fluorescent lightbulb) and oscillate back and forth by a few millimetres into the skin. This innovation is to introduce a very high frequency (i.e. beyond the rage of human hearing) micro oscillations hundredths of a millimetre) in the needle to ease the passage and reducing the pain felt by the tattoo recipient."

"Application defined by a partnership: the lead applicant has an advanced ultrasound ""driven"" needle that greatly improves the accuracy of delivering medicines to deep tissues (improved tissue penetration and highly visible on ultrasound scanners); the partner has a nanotechnology based agent that generates highly localised free radicals to enhance the effectiveness of cancer radiotherapy. This project enables these two companies to bring these two highly complementary technologies together and explore the possibility of a more accurate system of targeting radiotherapy that is less traumatic, more effective and that may offer a route to a cure. Uniting these two technologies opens up a considerable commercial potential for both parties. The vision is to propel both parties forward by developing a combination system that can drastically enhance the accuracy of treating challenging tumours in the head, neck and pancreas. To bring these two innovations together the feasibility of this approach must be explored. The applicants wish to understand how the combined system would be used to target a pancreatic tumour. The enclosed project will explore: * Configuration of advanced ""Active Needle"" that is suitable for the targeting of pancreatic tumours; * Use the above needle to validate biodistribution of the nanoparticulate radiotherapy enhancement agent in a mouse pancreatic cancer model; * Develop a future pre-clinical study protocol for the combined system validation; * Examine the relevant intellectual property landscape for this innovation and secure IP."

"Active Needle Technology Limited ""ANT"" are the developers of a specialised high frequency vibrating needle that aims to reduce needle placement errors associated with ultrasound guided interventional procedures. This will save time, lower the cost burden on the NHS and other healthcare providers and reduce the need for the patient to return because their medical procedures (biopsy or epidural) failed. The ANT team has progressed to stage of having a pre-production prototype of this vibrating needle. ANT's development pathway is blocked by a near term environmental and regulatory roadblock. In order to work, the needle must vibrate rapidly, and these vibrations are provided by a special ceramic material (piezomaterials) that contains high quantities of lead. This large lead content creates hazards during processing, limits applications (e.g., _in vivo_), and is environmentally toxic during disposal. As response, regulatory agencies world-wide, including the EU (RoSH Directive), have begun restricting its use, which has triggered a strong desire to identify new lead-free alternatives with comparable properties to those currently used. While the medical device industry is currently exempt from such restrictions (until 2019), ANT aims to be ahead of the game by developing lead-free piezomaterials in its needle guidance technology. A particular market of focus for ANT is Germany, hence having a lead-free product is consider to be a major market advantage. The challenge for ANT, and project motivation, is to identify and characterise the most suitable lead-free piezomaterials for ANT's needle. In particular, a major aspect of ANT's in-house development is the use of computer modelling to ensure the needle actuator delivers the required performance. Current computer models can't deal with lead-free piezoceramic. The innovation takes a number of forms: 1 - ANT's active needle approach is innovative in terms of clinical practice; 2 - to date nobody has used lead free piezomaterials in a medical device and; 3 - The refinement of current computer models so that lead-free piezomaterials can be designed and manufactured."