A deeper understanding of human development and disease is made possible partly through the study of genetically modified model organisms, such as the common mouse (Mus musculus). By genetically modifying such model organisms, scientists can activate, deactivate, or highlight particular characteristics. A genetically modified animal is generated by adding exogenous (foreign) genetic material to one or more embryonic cells at their earliest stages of development. Frequently, this exogenous genetic material consists of specially engineered DNA, which is introduced into a fertilized egg cell (zygote). When successfully introduced into the zygote, the exogenous DNA will be incorporated into the cell's own genome, and the animal that develops from the zygote will exhibit the genetic modification in all of its cells. The current devices and methods for generating genetically modified animals are inefficient, and/or difficult to use. The most common and efficient method for inserting new DNA into zygotes is by directly injecting a DNA solution through a tiny glass tube into the cell in a process called microinjection. Unfortunately, microinjection is quite inefficient (success rates are commonly between 1 and 5%), but often it is the only method for inserting DNA into eggs, zygotes, or early stage embryos. This thesis presents the design and testing of a micrometer sale, pumpless microelectromechanical system (MEMS) nanoinjector. Rather than use pumps and capillaries, the nanoinjector employs electrostatic charges to attract and repel DNA onto and off of the surface of a solid lance. The nanoinjector also includes a mechanical system for constraining the target cells during injection. Initial testing indicates the nanoinjector does not decrease cell viability, and it has a very high initial success rate (up to 90%). With the addition of an on-chip actuator, the nanoinjector could be packaged as an inexpensive, fully automated system, enabling efficient, high volume genetic modification of developing animals. Such a device would greatly increase the ease and speed of generating the model organisms needed to study such critical diseases such as Alzheimer's disease, cancer, and diabetes.

The capability of precisely controlling the kinetics of therapeutic delivery at the optimal location and rate for a given patient would have great potential to improve health and well-being in a range of current drug therapies (insulin, chemotherapeutics, vaccines, etc.). Indeed, if successfully developed, locally administered injectable drug delivery vehicles capable of remotely-triggered release would be the gold standard for many treatments. Multiple injectable nanocomposites have been investigated for this purpose that are generally comprised of a thermosensitive polymeric material and superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs generate heat when exposed remote alternating magnetic fields (AMFs), and the transfer of this heat to thermosensitive polymers can be used to control the release of therapeutics. Ideally, these systems would be capable of returning to their original state and basal release rate when the external AMF trigger is removed. Several novel injectable nanocomposite materials that explore interactions between SPIONs and thermosensitive polymers to mediate drug release, from the macroscale to the nanoscale, were developed and demonstrated to be capable of remotely-triggered, AMF-mediated enhanced release. The macroscale magnetic nanocomposites have thermosensitive hydrogel and/or microgel components that regulate release based on the heat produced from SPIONs in response to an external AMF. On the millimeter-scale, a microinjection system capable of producing thermosensitive hydrogel beads that could potentially incorporate SPIONs is described. On the nanoscale, nanoparticles with a glass transition temperature and thermosensitive microgels are combined with SPIONs and investigated for their remote, AMF-mediated release characteristics. The engineered macroscale and nanoscale systems are capable of up to ~4:1 and ~7:1 enhancements in release due to an AMF application, respectively, compared to the basal release rate. Collectively, these nanocomposites represent a promising stride towards improved remote-actuation of drug release and a stepping stone for future attempts at precisely controlling the site and kinetics of drug release. / Thesis / Doctor of Philosophy (PhD) / This thesis focuses on the development of nanocomposite materials that can be injected into a specific location in the body and deliver therapeutic drugs by a remote-controlled process. These nanocomposites are composed of magnetic particles and polymers that respond to changes in temperature. The combination of these materials results in nanocomposites that can change their properties in response to specific magnetic fields to switch from releasing drug slowly (or not at all) to releasing drug quickly on demand. The changes are fully reversible and solely depend on whether the external magnetic field is switched on or off. These novel systems offer an alternative to therapies that require frequent injections, such as insulin for diabetes, or therapies that need the drug to be released in very precise locations, such as cancer treatments, and could improve the safety, reduce the risk of side effects, and lower the cost of many medical treatments.