School of Management (SoM)

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Browsing School of Management (SoM) by Course name "PhD in Manufacturing"

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    Development of nanomip based sensors for drugs of abuse detection.
    (2018-02) D'aurelio, Roberta; Tothill, Ibtisam E.; Chianella, Iva
    This work presents the development of portable, yet highly sensitive and specific, sensor based on NanoMIPs EIS for the detection of cocaine and morphine at trace levels (sub-ppm). The molecularly imprinted polymer nanoparticles (nanoMIPs) were synthesised as the sensing elements using solid-phase synthesis approach at the University of Leicester. Cocaine nanoMIPs and morphine nanoMIPs particle size (dH) were measured using Dynamic Light Scattering (DLS) and were found to be 168.80±68.73 nm and 170.09±54.75 nm for cocaine nanoMIP and morphine nanoMIP respectively, thus highlighting a small batch to batch variations. The nanoMIPs were then covalently attached to the conventional screen-printed electrode (SPE), thus yielding a nanoMIP EIS sensor. The Faradic Electrochemical Impedance Spectroscopy (EIS) was applied to detect the analyte binding events, having 10 mM [Fe (CN) 6]³⁻/⁴⁻ in MOPS (10 mM, pH 7.4) as redox couple solution. The EIS was recorded at a 0.12 V potential over the frequency range from 0.1 Hz to 50 kHz with a modulation voltage of 10 mV. The cocaine nanoMIP EIS sensor, fabricated onto SPE, was optimised and was able to detect cocaine hydrochloride (salt form) dissolved in 10 mM MOPS (pH 7.4) in the linear range of 0.1 – 50 ng mL⁻¹ (R²=0.984) and with a LOD equal to 0.24 ng mL⁻¹ . The optimisation studies on the surface blocking agents guaranteed the absence of cross-reactivity towards other drugs, such as morphine and other cocaine adulterants, such as levamisole, caffeine and, partially, mannitol. The optimised sensor and assay conditions were replicated using interdigitated electrode (IDE), achieving an LOD (2.5 ng mL⁻¹), which will requires further optimisation. Analogously, the morphine nanoMIP EIS sensor, fabricated onto SPE, was optimised and tested against morphine salt dissolved in MOPS (pH 7.4) (0.1 – 50 ng mL⁻¹). The sensor was able to detect morphine in the linear range of 0.1- 10 ng mL⁻¹ (R² = 0.977) and achieving a LOD as low as 0.109 ng mL⁻¹. The optimised sensor was replicated using IDE, placed in a custom-made 3D printed IDE cable holder. The sensor achieved an LOD of 0.114 ng mL⁻¹ in a linear range of 0.01 to 5 ng mL⁻¹. Furthermore, a QCM platform with a fully automated microfluidic system was employed in this work to develop a multiplexing nanoMIPs QCM sensor for cocaine and morphine detection. The morphine nanoMIPs and cocaine nanoMIPs were respectively immobilised on spot 1 and spot 2 of a QCM sensor chip. Due to the required QCM signal enhancement, morphine and cocaine were separately adsorbed onto 40 nm gold nanoparticles (AuNPs). Increasing concentration (250 ng mL⁻¹ to 50 µg mL⁻¹) of each drug conjugated AuNPs were prepared in PBS (pH 7.4) and injected onto the nanoMIP QCM sensor. The nanoMIPs QCM sensor was able to detect morphine-AuNPs and cocaine-AuNPs, without any detectable cross-reactivity events, with the respective LOD equal to 0.191 µg mL-¹and 0.360 µg mL⁻¹. The morphine-AuNPs and cocaine-AuNPs detection binding data were fitted to 1:1 Langmuir binding model and the average (±SD) values of the KD were equal to 0.647±0.340 µM and 0.225±0.197 µM respectively, thus providing insight on the affinity binding. All the nanoMIPs sensors developed in this work are cheap, easy-to-use and portable (in the case of EIS) screening methods for drugs of abuse detection, thus being a valuable competitor to the current on-site screening methods.
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    ItemOpen Access
    Improving treatment outcomes through personalised medicine - assessment of disease activity in acromegaly.
    (2017) Gomez, Roy; White, Nicola
    Purpose Personalised Medicine (PM), also known as stratified medicine has been known to improve treatment outcomes in a wide variety of disease area settings. Individualising treatment based on patient needs may also offer cost benefits to healthcare spend. Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease related symptoms or patient’s perceived quality of life. Methods An assessment to gauge the need to have an easy and helpful tool which may support acromegaly management was elucidated through a multinational qualitative survey. Subsequently, a validated a tool was developed to measure disease activity in acromegaly to support decision-making in clinical practice through a 2 step-approach. Firstly, an international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Secondly, a panel of 21 renowned endocrinologists at pituitary centres (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. Results The international qualitative survey revealed that current treatment practice does have shortcomings in fully achieving disease control as well as identifying the need for a helpful solution to guide acromegaly care. As part of elucidating the most important disease activity indicators, from expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumour status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumour status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumour size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. Conclusion The validation study underlined the importance of IGF-I and tumour status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. A disease specific tool named Acromegaly Disease Activity Tool (ACRODAT) is in its final stages of development that will support clinicians in reviewing the disease activity in a holistic manner.