Poly(methyl methacrylate) (PMMA) has become an appealing material for manufacturing microfluidic chips, particularly for biomedical applications, because of its transparency and biocompatibility, making the development of an appropriate bonding strategy critical. In our research, we used acetic acid as a solvent to create a pressure-free assembly of PMMA microdevices. The acetic acid applied between the PMMA slabs was activated by microwave using a household microwave oven to tightly merge the substrates without external pressure such as clamps. The bonding performance was tested and a superior bond strength of 14.95 ± 0.77 MPa was achieved when 70% acetic acid was used. Over a long period, the assembled PMMA device with microchannels did not show any leakage. PMMA microdevices were also built as a serpentine 2D passive micromixer and cell culture platform to demonstrate their applicability. The results demonstrated that the bonding scheme allows for the easy assembly of PMMAs with a low risk of clogging and is highly biocompatible. This method provides for a simple but robust assembly of PMMA microdevices in a short time without requiring expensive instruments.
Alzheimer’s disease (AD) is a neurodegenerative disorder, comprising 70% of dementia diagnoses worldwide and affecting 1 in 9 people over the age of 65. However, the majority of its treatments, which predominantly target the cholinergic system, remain insufficient at reversing pathology and act simply to slow the inevitable progression of the disease. The most recent neurotransmitter-targeting drug for AD was approved in 2003, strongly suggesting that targeting neurotransmitter systems alone is unlikely to be sufficient, and that research into alternate treatment avenues is urgently required. Neuromodulators are substances released by neurons which influence neurotransmitter release and signal transmission across synapses. Neuromodulators including neuropeptides, hormones, neurotrophins, ATP and metal ions display altered function in AD, which underlies aberrant neuronal activity and pathology. However, research into how the manipulation of neuromodulators may be useful in the treatment of AD is relatively understudied. Combining neuromodulator targeting with more novel methods of drug delivery, such as the use of multi-targeted directed ligands, combinatorial drugs and encapsulated nanoparticle delivery systems, may help to overcome limitations of conventional treatments. These include difficulty crossing the blood-brain-barrier and the exertion of effects on a single target only. This review aims to highlight the ways in which neuromodulator functions are altered in AD and investigate how future therapies targeting such substances, which act upstream to classical neurotransmitter systems, may be of potential therapeutic benefit in the sustained search for more effective treatments.