Ultrasound-enhanced fine-needle aspiration for biopsy: From device development to in vivo human validation

A hypodermic needle is a widely used medical instrument. With more than 16 billion needles used annually, it is an essential instrument of modern medicine. Medical needles are primarily used to deliver or draw material to or from a patient, playing a crucial role in various medical procedures. Despite the broad use of needles, limited technological improvements have been made to them over the last decades, leading to urgent unmet needs in applications such as biopsy. Biopsy is a medical procedure that aims to collect tissue from a suspected lesion for diagnosis. The analysis is intended to define what pathology is present in the target tissue and to decide on the potential treatment. While diagnostic techniques have improved, the quantity of tissue required has only grown due to the increasing range of assessment, each of them requiring part of the sample. Moreover, the tissue quantity and representativeness of the lesion is limited by the current techniques. To address this unmet clinical need, an Ultrasound-enhanced Fine-Needle Aspiration Biopsy (USeFNAB) has been proposed. USeFNAB utilizes ultrasonic actuation at the needle tip (peak-to-peak displacement < 200 μm) to detach the cells and tissue construct from the target. Combined with low pressure, USeFNAB aims to collect more tissue than the state-of-the-art methods to address the demand for increased tissue required for additional pathological analysis. To date, USeFNAB instrument has not been optimized in terms of power efficiency, ergonomics and size, and validation in human ex vivo and in vivo tissue has been missing. The aim of this Thesis was to develop a novel USeFNAB device capable of providing ultrasonic movement at the needle tip efficiently. This would allow miniaturization, battery integration, and improvement of the safety of the device. Once the device configurations were optimized in silico and prototyped, a validation of USeFNAB in tissue was conducted. USeFNAB was first tested on benign ex vivo human tonsils, and then on ex vivo human neo-plastic tissues (pleomorphic adenomas and head and neck cancers). Finally, the benefits of USeFNAB were demonstrated in a clinical trial on in vivo human pleomorphic adenomas. The results showed that the USeFNAB was capable to provide a flexural actuation at the needle tip with up to 73% electrical-to-acoustical power efficiency. It also demonstrated an increase in terms of mass collection in ex vivo human tissue by 2-7× compared to state-of-the-art needle biopsies without compromising the diagnosis outcome. Finally, in the in vivo clinical setting, USeFNAB showed a tissue area increase on the histological slide by 1.7-3.4× without compromising the diagnosis or increasing complications during the procedure as compared to state-of-the-art needle biopsies. The findings in this Thesis show promise for the USeFNAB to be the next-generation tool for cancer diagnosis. They also open avenues for applying ultrasound-enhanced medical needles to other applications, such as therapy.