Manufacture of silicon microneedles for drug & vaccine delivery

This project will develop high-volume, quality controlled, low-cost, bespoke, silicon microneedle (MN) devices for specialised Point of Care (POC) health applications. Device specifications will be defined by a comprehensive characterisation and analysis of human skin parameters (elasticity, deformation, epidermal thickness at different sites and between different people of different ages), with respect to MN delivery A range of novel MN products will be tested in clinical skin models to demonstrate their utility for easy-application and painless transdermal injection in drug and vaccine delivery.
The key benefit of silicon MNs is the flexibility, scalability of manufacturing; it is this aspect that we focus on in this application, developing personalised but scalable manufacture for personalised medicine.
The project combines microfabrication and manufacturing expertise (SU / SPTS) with pre-clinical and clinical results from Cardiff University (CU). We will develop novel hollow MN array drug and vaccine delivery systems and demonstrate their potential in clinical practice. Considerably finer and shorter than any hypodermic syringe needle, MN devices are relatively painless, (they do not puncture deep enough into the skin to stimulate pain), and cause appreciably less damage to skin than traditional hypodermics. This is critical in where patients will require regular therapy.
MNs will provide targeted therapy to the appropriate skin compartment. E.g. in vaccination, administering antigens to the epidermis (the top 75-150 um of skin) where the immune processing Langerhans cells reside will provide a robust,whole body immune response to the vaccine. Targeting of this zone may lead to a more efficient immune response (potentially without the need for potentially harmful adjuvants) and hence dose-sparing of the difficult to manufacture vaccine.
A completely novel plasma etch and masking process will be used (SU / SPTS) to fabricate a range of sharp, hollow MNs up to 1mm in length. Currently, sharp MNs are produced using a wet chemical etch or a combined wet and plasma etch process. Our new flexible, cost-effective plasma etch process will be used to manufacture a range of MNs of different heights for personalised drug and vaccine delivery, based on the results of skin parameter testing.
Our novel bevelled MN design - developed using SPTS' deep silicon etch technology - will facilitate MN skin penetration using low injection forces. The new, simple MN drug / vaccine delivery system could revolutionise the multi billion dollar drug delivery markets enabling for the first time the effective transcutaneous delivery of a wide range of low molecular weight drug molecules including: diclofenac, ketoprofen, methotrexate, sumatriptan, methyl nicotinate and lidocaine, and targeted vaccine delivery against influenza, hepatitis C, measles, polio, rabies and tuberculosis. Optimisation of hollow MN designs will allow injection of viable drug and vaccine dosages.
Manufacture of hollow silicon MNs also opens up a whole new field of novel applications in fluid sampling combined with sensor diagnostics. Extracting interstitial fluid in volumes substantial enough for analysis will facilitate "pain free" testing of small analyte molecules. Preliminary studies will evaluate the novel MN products arising from this project for potential use in glucose testing .
Scale-up of device fabrication from small samples to full wafers, to multi-wafer production, will be achieved through integral partner SPTS' wafer-cassette loaded, multi-process-chamber tools. SPTS, the global leader in semiconductor and MEMS process equipment, is the ideal partner for high-volume, low-cost manufacture of specialised silicon MN products. SPTS will ensure manufacturing methods and materials used to make the MN devices are cost effective for scale-up production.
The MN market is ripe for exploitation using new MN designs, capable of being manufactured on a volume scale.

Academic impact has been outlined in the "Beneficiaries" section. It must be stressed that SU's involvement in the EPSRC partnership will elevate them from micro/nanofabrication specialists to an internationally leading group in the MNs and microfluidics sector. Knowledge transfer between the partners will produce scientific advancements in MN design and provide new engineering solutions to medical problems.
Patient benefits:
MN delivery could revolutionise the prevention and treatment of acute and chronic diseases by facilitating simple, painless, cheap and scar free drug and vaccine delivery into the skin. Cost efficiency will be key as the microneedle platform will need to be exploited for a wide range of patients in a variety of territories. Less invasive, and more user-friendly MN injection (compared to conventional hypodermic injections) for immunisation and drug delivery applications would significantly enhance patients' quality of life through more effective and convenient treatment. The reduction in injection pain will encourage greater compliance in chronic diseases such as diabetes and improved adherence with childhood immunisation schedules. MN devices will be easy to use and could possibly be administered by the patient themselves - saving the NHS valuable time and manpower.
Industry impact and Intellectual Property (IP):
The main economic impacts to the industrial partners will be in sales of etch / deposition equipment related to production scale fabrication of the MN devices for SPTS and MN product sales from a future spin-out company from Swansea and Cardiff.
A conservative scenario, where MN kits are used for 5% of the forecast $400mn market would equate to 1 million MN chips - requiring 5 SPTS modules, generating $3m revenue per annum and extra jobs at SPTS. Revenue is expected to grow significantly over a 5 year period.
SPTS will be first to exploit traditional semiconductor and MEMS manufacturing processes for healthcare, stealing a march on their competitors in the $2bn BioMEMS market.
SPTS have calculated the cost per MN die as $0.9. At this cost, the MNs become viable for a host of other drug / vaccine delivery and fluid extraction applications.
Process flows for MN fabrication developed by SPTS and SU, could be licensed by customers, and used in Dry Etch/CVD foundries world-wide. This is SPTS' main interest as it allows the etch technology to be used in many diverse MN markets.
Initial prior art searches have revealed freedom to operate in MN design and in specific application areas and there is potential for prolific IP generation for all partners. Specific IP generated for the MN fabrication steps would belong to SPTS and SU. SU & CU would benefit from IP licensing agreements, spin-off technologies and high impact journal publications. Publication will be encouraged where not damaging to commercial interests.
Cardiff, have extensive MN expertise and will build a strong IP portfolio and further credibility in the rapidly emerging growing $400mn drug MN delivery market (Catapult).
Following clinical testing the EPSRC partners will link with foundries to manufacturer the MN devices for pharmaceutical companies.
Manufacturing and supply will be licensed with established supply chain companies leading to further job creation and MN products.
SU's Department of Research and Innovation and Cardiff's Research and Commercial Division will assist in IP protection, securing funding for clinical trials and negotiating licensing deals with Dr. Guy's and Prof. Birchall's established network of commercialisation partners including: Ig Innovations, 3M Healthcare, KPMG, Renishaw, P&S Nano, and Picofluidics - who'd all be interested in exploiting aspects of the MN technology.