Development of a dissolvable microneedle influenza vaccine patch

Delivery of large molecular weight biological molecules to the epidermis and dermis is constrained by the tough outer layer of the epidermis, the stratum corneum (sc). Microneedle technologies attempt to overcome this physical barrier using sharp micron-size projections to penetrate the sc. Dissolvable microneedles (DMN), are a particular microneedle design whereby the needle structure is composed of a soluble matrix that upon application to the skin, dissolves releasing the vaccine load into skin. This thesis examines (1) the formulation and processing considerations around DMN fabrication, (2) the immunogenicity of DMN containing trivalent influenza vaccine (TIV) in pre-clinical mouse and pig models and (3) the thermostability of these DMN formulations during storage. The results demonstrate the importance of formulation for microneedle formation and mechanical strength. Trehalose and polyvinylalcohol based formulations produced optimal microneedle structures and were amenable to piezoelectric dispensing; allowing for precise multi-layered DMN to be fabricated. The effect of drying conditions was assessed and found to be critical for DMN mechanical strength and skin penetration. The antibody responses to TIV generated by DMN-mediated vaccination were comparable or greater to those induced by immunization with a commercial TIV via the IM route in mice. DMN mediated immunisation resulted in a significantly broader humoral response to heterotypic influenza viruses compared to IM delivery. Stored at 40°C, a licensed seasonal influenza vaccine incorporated into DMN array was thermostable for at least 6 month as determined by Single Radial Immunodiffusion and immunogenicity in mice. The thesis advances the field of DMN influenza vaccination by elucidating important processing and formulation considerations in the fabrication of highly reproducible DMN. It also demonstrated that DMN can induce broader, larger humoral responses than conventional IM administration while demonstrating enhanced accelerated stability. Crucially, this works advances an automated fabrication system that will allow for clinical translation of DMN.

Hardware design of cryptographic accelerators

With the rapid growth of the Internet and digital communications, the volume of sensitive electronic transactions being transferred and stored over and on insecure media has increased dramatically in recent years. The growing demand for cryptographic systems to secure this data, across a multitude of platforms, ranging from large servers to small mobile devices and smart cards, has necessitated research into low cost, flexible and secure solutions. As constraints on architectures such as area, speed and power become key factors in choosing a cryptosystem, methods for speeding up the development and evaluation process are necessary. This thesis investigates flexible hardware architectures for the main components of a cryptographic system. Dedicated hardware accelerators can provide significant performance improvements when compared to implementations on general purpose processors. Each of the designs proposed are analysed in terms of speed, area, power, energy and efficiency. Field Programmable Gate Arrays (FPGAs) are chosen as the development platform due to their fast development time and reconfigurable nature. Firstly, a reconfigurable architecture for performing elliptic curve point scalar multiplication on an FPGA is presented. Elliptic curve cryptography is one such method to secure data, offering similar security levels to traditional systems, such as RSA, but with smaller key sizes, translating into lower memory and bandwidth requirements. The architecture is implemented using different underlying algorithms and coordinates for dedicated Double-and-Add algorithms, twisted Edwards algorithms and SPA secure algorithms, and its power consumption and energy on an FPGA measured. Hardware implementation results for these new algorithms are compared against their software counterparts and the best choices for minimum area-time and area-energy circuits are then identified and examined for larger key and field sizes. Secondly, implementation methods for another component of a cryptographic system, namely hash functions, developed in the recently concluded SHA-3 hash competition are presented. Various designs from the three rounds of the NIST run competition are implemented on FPGA along with an interface to allow fair comparison of the different hash functions when operating in a standardised and constrained environment. Different methods of implementation for the designs and their subsequent performance is examined in terms of throughput, area and energy costs using various constraint metrics. Comparing many different implementation methods and algorithms is nontrivial. Another aim of this thesis is the development of generic interfaces used both to reduce implementation and test time and also to enable fair baseline comparisons of different algorithms when operating in a standardised and constrained environment. Finally, a hardware-software co-design cryptographic architecture is presented. This architecture is capable of supporting multiple types of cryptographic algorithms and is described through an application for performing public key cryptography, namely the Elliptic Curve Digital Signature Algorithm (ECDSA). This architecture makes use of the elliptic curve architecture and the hash functions described previously. These components, along with a random number generator, provide hardware acceleration for a Microblaze based cryptographic system. The trade-off in terms of performance for flexibility is discussed using dedicated software, and hardware-software co-design implementations of the elliptic curve point scalar multiplication block. Results are then presented in terms of the overall cryptographic system.

Secure architectures for pairing based public key cryptography

Along with the growing demand for cryptosystems in systems ranging from large servers to mobile devices, suitable cryptogrophic protocols for use under certain constraints are becoming more and more important. Constraints such as calculation time, area, efficiency and security, must be considered by the designer. Elliptic curves, since their introduction to public key cryptography in 1985 have challenged established public key and signature generation schemes such as RSA, offering more security per bit. Amongst Elliptic curve based systems, pairing based cryptographies are thoroughly researched and can be used in many public key protocols such as identity based schemes. For hardware implementions of pairing based protocols, all components which calculate operations over Elliptic curves can be considered. Designers of the pairing algorithms must choose calculation blocks and arrange the basic operations carefully so that the implementation can meet the constraints of time and hardware resource area. This thesis deals with different hardware architectures to accelerate the pairing based cryptosystems in the field of characteristic two. Using different top-level architectures the hardware efficiency of operations that run at different times is first considered in this thesis. Security is another important aspect of pairing based cryptography to be considered in practically Side Channel Analysis (SCA) attacks. The naively implemented hardware accelerators for pairing based cryptographies can be vulnerable when taking the physical analysis attacks into consideration. This thesis considered the weaknesses in pairing based public key cryptography and addresses the particular calculations in the systems that are insecure. In this case, countermeasures should be applied to protect the weak link of the implementation to improve and perfect the pairing based algorithms. Some important rules that the designers must obey to improve the security of the cryptosystems are proposed. According to these rules, three countermeasures that protect the pairing based cryptosystems against SCA attacks are applied. The implementations of the countermeasures are presented and their performances are investigated.

Cryptographic coprocessors for embedded systems

In the field of embedded systems design, coprocessors play an important role as a component to increase performance. Many embedded systems are built around a small General Purpose Processor (GPP). If the GPP cannot meet the performance requirements for a certain operation, a coprocessor can be included in the design. The GPP can then offload the computationally intensive operation to the coprocessor; thus increasing the performance of the overall system. A common application of coprocessors is the acceleration of cryptographic algorithms. The work presented in this thesis discusses coprocessor architectures for various cryptographic algorithms that are found in many cryptographic protocols. Their performance is then analysed on a Field Programmable Gate Array (FPGA) platform. Firstly, the acceleration of Elliptic Curve Cryptography (ECC) algorithms is investigated through the use of instruction set extension of a GPP. The performance of these algorithms in a full hardware implementation is then investigated, and an architecture for the acceleration the ECC based digital signature algorithm is developed. Hash functions are also an important component of a cryptographic system. The FPGA implementation of recent hash function designs from the SHA-3 competition are discussed and a fair comparison methodology for hash functions presented. Many cryptographic protocols involve the generation of random data, for keys or nonces. This requires a True Random Number Generator (TRNG) to be present in the system. Various TRNG designs are discussed and a secure implementation, including post-processing and failure detection, is introduced. Finally, a coprocessor for the acceleration of operations at the protocol level will be discussed, where, a novel aspect of the design is the secure method in which private-key data is handled