Continuous Flow Platforms for the Synthesis and Optimisation of Polymeric Materials via RAFT Polymerisation

This thesis focuses on the development and use of continuous flow platforms to perform the synthesis and subsequent chain extension of poly(dimethylacrylamide) (PDMAm), via reversible addition fragmentation chain transfer (RAFT) polymerisation, in order to obtain a range of polymeric nanoparticles. Initially, a stainless-steel flow reactor was developed and polymerisation kinetics were obtained for all RAFT polymerisations in both batch and flow reactors. Whilst good control over the polymerisations were observed for both batch and flow reactors slightly accelerated kinetics were observed in flow reactors. A range of poly(dimethylacrylamide)- poly(diacetone acrylamide) based polymerics nanoparticles were then synthesised in the flow reactor. A series of spherical micelles were successfully formed with particle size increasing with PDAAm DP. However, significant fouling was observed during the synthesis of higher order morphologies and no pure phases were obtained. A PFA flow reactor was then developed for synthesising higher order polymeric nanoparticles. At the same time polymerisation kinetics were also accelerated by using an initiator (VA-044) with a significantly higher rate of decomposition. In order to more easily monitor the accelerated reaction kinetics a benchtop NMR was placed at the reactor outlet to allow for continuous online monitoring of the polymerisation. A series of PDMAm-PDAAm spherical nanoparticles were successfully synthesised in the flow reactor in 20 minutes. When targeting higher order morphologies sphere/worm and worm/vesicle mixed phases were succesfully formed. Pure vesicle phases were only formed when high PDAAm DP (> 200) were targeted due to limited chain mobility and poor mixing in the flow reactor. Finally, an automated flow reactor platform that incorporated NMR and GPC was developed and used to monitor and screen reaction conditions for the RAFT solution polymerisations of dimethylacrylamide (DMAm) and tert-butylacrylamide. Furthermore, incorporation of an advanced machine learning algorithm (TS-EMO) allowed simultaneous self-optimisation of these polymerisations for both conversion and dispersity

In-situ aldehyde-modification of self-assembled acyl hydrazide hydrogels and dynamic component selection from complex aldehyde mixtures

Self-assembled hydrogels based on the industrially-relevant 1,3:2,4-dibenzylidene sorbitol framework functionalised with reactive acyl hydrazides (DBS-CONHNH2) peripheral groups react with aldehydes without disrupting the nanoscale gel network, adapting gel performance, and dynamically selecting specific aldehyde components from complex mixtures

Enhancing the scalability of crystallization-driven self-assembly using flow reactors

Anisotropic materials have garnered significant attention due to their potential applications in cargo delivery, surface modification, and composite reinforcement. Crystallization-driven self-assembly (CDSA) is a practical way to access anisotropic structures, such as 2D platelets. Living CDSA, where platelets are formed by using seed particles, allows the platelet size to be well controlled. Nonetheless, the current method of platelet preparation is restricted to low concentrations and small scales, resulting in inefficient production, which hampers its potential for commercial applications. To address this limitation, continuous flow reactors were employed to improve the production efficiency. Flow platforms ensure consistent product quality by maintaining the same parameters throughout the process, circumventing batch-to-batch variations and discrepancies observed during scale-up. In this study, we present the first demonstration of living CDSA performed within flow reactors. A continuous flow system was established, and the epitaxial growth of platelets was initially conducted to study the influence of flow parameters such as temperature, residence time, and flow rate on the morphology of platelets. Comparison of different epitaxial growth manners of seeds and platelets was made when using seeds to perform living CDSA. Size-controllable platelets from seeds can be obtained from a series flow system by easily tuning flow rates. Additionally, uniform platelets were continuously collected, exhibiting improved size and dispersity compared to those obtained in batch reactions

Comparison of T-cell Receptor Diversity of people with Myalgic Encephalomyelitis versus controls

Objective: Myalgic Encephalomyelitis (ME; sometimes referred to as Chronic Fatigue Syndrome) is a chronic disease without laboratory test, detailed aetiological understanding or effective therapy. Its symptoms are diverse, but it is distinguished from other fatiguing illnesses by the experience of post-exertional malaise, the worsening of symptoms even after minor physical or mental exertion. Its frequent onset after infection suggests autoimmune involvement or that it arises from abnormal T-cell activation. Results: To test this hypothesis, we sequenced the genomic loci of and T-cell receptors (TCR) from 40 human blood samples from each of four groups: severely affected people with ME; mildly or moderately affected people with ME; people diagnosed with Multiple Sclerosis, as disease controls; and, healthy controls. Seeking to automatically classify these individuals’ samples by their TCR repertoires, we applied P-SVM, a machine learning method. However, despite working well on a simulated data set, this approach did not allow statistically significant partitioning of samples into the four subgroups. Our findings do not support the hypothesis that blood samples from people with ME frequently contain altered T-cell receptor diversity

Recent trends in advanced polymer materials in agriculture related applications

Over the past few decades, advanced polymeric materials have gained popularity in the development of sustainable agricultural applications. Smart polymeric systems have extensively contributed to the agricultural industry by increasing the efficiency of pesticides, herbicides, and fertilizers by facilitating controlled release systems and, therefore, enabling lower doses to be used. Superabsorbent polymeric materials have been used as soil conditioners to control the impact of drought, whereas polycationic polymers have been utilized for plant bioengineering. These functions in the environment are complemented by applications within plants as part of the developing range of tools for genetically transforming plants in order to increase productivity and disease resistance. This Review will summarize and discuss the recent developments in the design and application of advanced polymeric systems for precision agriculture related applications. The design criteria of the polymers employed to date, such as polymer structure, as well as the properties of polymer nanoparticles including shape and size will be discussed, and the key findings in the related area will be highlighted. Finally, we will identify future directions for the exploration of functional polymers with the ultimate aim of advancing sustainable agriculture

Benchtop flow-NMR for rapid online monitoring of RAFT and free radical polymerisation in batch and continuous reactors

A “Benchtop” NMR spectrometer is used for detailed monitoring of controlled and free radical polymerisations performed in batch and continuous reactors both offline and in real-time. This allows detailed kinetic analysis with unprecedented temporal resolution for reactions which reach near completion in under five minutes

Heterometallic lanthanide complexes with site-specific binding that enable simultaneous visible and NIR-emission

Macrocyclic lanthanide complexes have become widely developed due to their distinctive luminescence characteristics and wide range of applications in biological imaging. However, systems with sufficient brightness and metal selectivity can be difficult to produce on a molecular scale. Presented herein is the stepwise introduction of differing lanthanide ions in a bis-DO3A/DTPA scaffold to afford three trinuclear bimetallic [Ln2Ln’] lanthanide complexes with site-specific, controlled binding [(Yb2Tb), (Eu2Tb), (Yb2Eu)]. The complexes display simultaneous emission from all LnIII centers across the visible (TbIII, EuIII) and near infra-red (YbIII) spectrum when excited via phenyl ligand sensitization at a wide range of temperatures and are consequently of interest for exploiting imaging in the near infra-red II biological window. Analysis of lifetime data over a range of excitation regimes reveals intermetallic communication between TbIII and EuIII centers and further develops the understanding of multimetallic lanthanide complexes

Polymersome-Encapsulated Chemosensors: New Design Strategies toward Biofluid-Applicable Cucurbit[7]uril Indicator Displacement Assays

The development of supramolecular cucurbit[7]uril-based chemosensors for the detection of bioanalytes in biofluids such as untreated human serum and inside cells is a challenging task due to competition with proteins and inorganic salts. In this contribution, we show that the encapsulation of cucurbit[7]uril-based chemosensors in polymersomes can prevent deactivation, rendering the chemosensors operational in human serum and inside cells. We found that polymersomes with a hydrophilic poly-[N,N-dimethylacrylamide] corona, especially those smaller than 200 nm, exhibit greater permeability to small bioactive molecules compared with polymersomes with a bulkier poly(ethylene glycol) corona. Furthermore, analytes characterized by intermediate lipophilicity, low charge density, and a rigid structure display enhanced permeability through the polymersomes. The polymer membrane serves as a selective filter that allows small molecules to pass through a chemosensor while larger proteins are held outside the polymersome. In addition to providing a new approach for stabilizing chemosensors in protein-rich media, this study underscores the potential utility of polymersome-encapsulated chemosensors in investigating membrane permeability

The Potential of Current Noninvasive Wearable Technology for the Monitoring of Physiological Signals in the Management of Type 1 Diabetes: Literature Survey

BackgroundMonitoring glucose and other parameters in persons with type 1 diabetes (T1D) can enhance acute glycemic management and the diagnosis of long-term complications of the disease. For most persons living with T1D, the determination of insulin delivery is based on a single measured parameter—glucose. To date, wearable sensors exist that enable the seamless, noninvasive, and low-cost monitoring of multiple physiological parameters.ObjectiveThe objective of this literature survey is to explore whether some of the physiological parameters that can be monitored with noninvasive, wearable sensors may be used to enhance T1D management.MethodsA list of physiological parameters, which can be monitored by using wearable sensors available in 2020, was compiled by a thorough review of the devices available in the market. A literature survey was performed using search terms related to T1D combined with the identified physiological parameters. The selected publications were restricted to human studies, which had at least their abstracts available. The PubMed and Scopus databases were interrogated. In total, 77 articles were retained and analyzed based on the following two axes: the reported relations between these parameters and T1D, which were found by comparing persons with T1D and healthy control participants, and the potential areas for T1D enhancement via the further analysis of the found relationships in studies working within T1D cohorts.ResultsOn the basis of our search methodology, 626 articles were returned, and after applying our exclusion criteria, 77 (12.3%) articles were retained. Physiological parameters with potential for monitoring by using noninvasive wearable devices in persons with T1D included those related to cardiac autonomic function, cardiorespiratory control balance and fitness, sudomotor function, and skin temperature. Cardiac autonomic function measures, particularly the indices of heart rate and heart rate variability, have been shown to be valuable in diagnosing and monitoring cardiac autonomic neuropathy and, potentially, predicting and detecting hypoglycemia. All identified physiological parameters were shown to be associated with some aspects of diabetes complications, such as retinopathy, neuropathy, and nephropathy, as well as macrovascular disease, with capacity for early risk prediction. However, although they can be monitored by available wearable sensors, most studies have yet to adopt them, as opposed to using more conventional devices.ConclusionsWearable sensors have the potential to augment T1D sensing with additional, informative biomarkers, which can be monitored noninvasively, seamlessly, and continuously. However, significant challenges associated with measurement accuracy, removal of noise and motion artifacts, and smart decision-making exist. Consequently, research should focus on harvesting the information hidden in the complex data generated by wearable sensors and on developing models and smart decision strategies to optimize the incorporation of these novel inputs into T1D interventions.</p

Harnessing Cytosine for Tunable Nanoparticle Self-Assembly Behavior Using Orthogonal Stimuli

Nucleobases control the assembly of DNA, RNA, etc. due to hydrogen bond complementarity. By combining these unique molecules with state-of-the-art synthetic polymers, it is possible to form nanoparticles whose self-assembly behavior could be altered under orthogonal stimuli (pH and temperature). Herein, we report the synthesis of cytosine-containing nanoparticles via aqueous reversible addition-fragmentation chain transfer polymerization-induced self-assembly. A poly(N-acryloylmorpholine) macromolecular chain transfer agent (mCTA) was chain-extended with cytosine acrylamide, and a morphological phase diagram was constructed. By exploiting the ability of cytosine to form dimers via hydrogen bonding, the self-assembly behavior of cytosine-containing polymers was altered when performed under acidic conditions. Under these conditions, stable nanoparticles could be formed at longer polymer chain lengths. Furthermore, the resulting nanoparticles displayed different morphologies compared to those at pH 7. Additionally, particle stability post-assembly could be controlled by varying pH and temperature. Finally, small-angle X-ray scattering was performed to probe their dynamic behavior under thermal cycling