The monitoring of blood glucose is a key aspect of diabetes care in limiting the negative effects of hyperglycaemia to both the microvasculature and macrovasculature. Self-monitoring of blood glucose (SMBG) gives an indication of blood glucose at a specific point in time and is recommended to be carried out four times daily. However, due to the inconvenience and associated pain of blood withdrawal, SMBG is often carried out less frequently than recommended or not at all. Extraction and subsequent determination of glucose in interstitial fluid (ISF) using microneedles (MNs) is an emerging area of research due to their minimally invasive nature and lack of associated pain. In this manuscript, a novel method for the fabrication of a hollow microneedle device is reported. The microneedle produced had a sharp bevelled edge and was 400 µm in length. Additionally, a paper backplate embedded with a colorimetric system for the rapid visual determination of glucose in simulated ISF was developed and paired with the hollow MN. This device rapidly extracted simulated ISF within five seconds and its ability to produce a glucose concentration dependent colour change within 30 s was demonstrated. Using this approach, it was possible to discriminate between glucose concentrations in normal glycaemia (4-7 mM) and hyperglycaemia (>7 mM) ranges using the naked eye. While further development is required, the results herein highlight the potential of this device to be used as a blood-free minimally invasive approach to glucose monitoring.

Mastectomy is common surgical treatment used in the management of breast cancer but has associated physical and psychological consequences for the patient. Breast conservation surgery (BCS) is an alternative to mastectomy but is only possible when the tumour is of an appropriate size. Neo-adjuvant chemotherapy has been successfully used to downstage tumours and increase the number of patients eligible for BCS. However, the chemotherapies used in this approach are non-targeted and often result in significant side effects to the patient. In this manuscript, we evaluate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver Rose Bengal-mediated sonodynamic therapy (SDT) in combination with paclitaxel (PTX) and doxorubicin (Dox) chemotherapy as a potential treatment for breast cancer. Efficacy of the combined treatment was determined in a threedimensional (3D) spheroid model of human breast cancer and in a murine model of the disease bearing subcutaneous MCF-7 tumours. The results demonstrated a significant reduction in both the cell viability of spheroids and tumour volume following treatment with the drug loaded microbubbles and ultrasound compared to targets treated with the drug loaded microbubbles alone or a Cremophor EL suspension of PTX and Dox. In addition, the weight of animals that received the microbubble treatment was unchanged throughout the study while a reduction of 12.1% was observed for animals treated with a Cremophor suspension of PTX/Dox. These results suggest that UTMD-mediated chemo-sonodynamic therapy is an efficacious and well tolerated approach for the treatment of breast cancer.

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