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Digital archive of theses discussed at the University of Pisa


Thesis etd-05142014-175956

Thesis type
Tesi di dottorato di ricerca
Thesis title
Microneedles for minimally-invasive transdermal medical applications
Academic discipline
Course of study
tutor Ing. Barillaro, Giuseppe
tutor Prof. Nannini, Andrea
  • drug delivery
  • fluid sampling
  • glucose measuring
  • microneedles
Graduation session start date
This thesis deals with design, fabrication and characterization of novel devices for minimally invasive transdermal applications, for both withdrawing -testing liquid and improving transdermal drug delivery.
At first, a new concept glucose self-monitoring device, for measuring glycaemia without causing pain or bleeding is presented. This device, called glucose pen, allows point-of-care glucose monitoring in a minimally invasive way, by avoiding both bleeding and pain caused and reducing, at the same time, the risk of infection in respect to the conventional method of glucose self monitoring. The glucose pen contains a silicon dioxide microneedle array, which samples interstitial fluid after being inserted into the skin, and a glucose biosensor for testing the sampled drop. Both fabrication process and mechanical characterization of the microneedle array is reported. Besides, the design of all the glucose pen components (circuit for glucose related signal driving and read-out, glucose sensor and microneedle array assembling into a disposable head, system for clamping the disposable head to the pen, mechanical actuating system for microneedle movement and insertion into the skin) is showed.
Then, a fabrication process based on the silicon electrochemical micromachining technology for realizing out-of-plane microneedles is reported. The developed process allowed to fabricate both sharp and flat microneedle array, to be inserted into the skin so as to improve skin permeability to a model drug and, as a consequence, the amount of drug delivered in a transdermal path.
Finally, the design and fabrication of a minimally invasive device for transdermal injection and sampling applications, carried out at Dimes Technology Center, Delft (NL), is reported. The proposed devices are fabricated by means of a wafer level process based on a Deep Reactive Ion Etching and consist in an array of hollow flat silicon microneedles, connected with a reservoir, integrated on the back-side of the device itself. The realized devices, which are very different in microneedle shape, inner diameter and array density, can be used for both drug delivery or for in-situ fluid analysis. Besides, the proposed process is suitable to perform an industrial production of microneedle array, since it is wafer level and is based on a well known industrial process. A further application of these devices could be sensing or stimulating biopotentials, since they can be covered with conductive layer, as titanium nitride.