In this paper, we present the theoretical background, design, fabrication and characterization of a micromachined chamber assisting the fluidic self-assembly of micro-electro-mechanical systems in a bulk liquid. Exploiting bubble-induced acoustic microstreaming, several structurally-robust driving modes are excited inside the chamber. The modes promote the controlled aggregation and disaggregation of microcomponents relying on strong and reproducible fluid mixing effects achieved even at low Reynolds numbers. The functionality of the microfluidic chamber is demonstrated through the fast and repeatable geometrical pairing and subsequent unpairing of polymeric microcylinders. Relying only on drag and radiation forces and on the natural hydrophobicity of SU-8 in aqueous solutions, assembly yields of approximately 50% are achieved in no longer than ten seconds of agitation. The system can stochastically control the assembly process and significantly reduce the time-to-assembly of building blocks.

Integration of valve like structures into microfluidic chips is a key factor for the usability of many microfluidic systems. One approach is utilization of thin PDMS layers as flexible membranes which can be closely packed on the microfluidic chips. These flexible membranes can be deformed by pneumatic actuation, closing or opening the fluidic channel of the corresponding valve. However, PDMS is permeable to gases and this permeability gets non-negligible for common valve layer thicknesses and pressure gradients. This factor restricts the usage of PDMS valves in microfluidic systems, as gas bubbles are strictly prohibited in many applications. Here two methods avoiding the intrusion of gas into the microfluidic channels are introduced and investigated. The first is based on an oil droplet placed in the dead end pneumatic channel of the valve, the second utilizes a parylene coating to make PDMS impermeable to gases. The parylene layer could not completely suppress the gas intrusion into the fluidics of the valve and additionally influenced the sealing capabilities of the valve. The oil droplet, in contrast, suppressed the permeability of the valve completely and provides a straight forward solution. In the experimental setup a novel valve design is introduced and characterized. Sealing capabilities, hydraulic resistance and lifetime are measured, dead and internal volume are calculated to describe the capabilities of thin membrane PDMS valves. These values are of interest if the valves are to be used industrially. The design introduced here is easy to fabricate and requires low alignment accuracy: it uses a Polycarbonate/PDMS sandwich, bonded by a APTES coating. Combining the simplicity of the valve design and the low cost fabrication methods and materials needed, the valve is perfectly suited as a disposable consumable.

Abstract-Self-assembly is a key coordination mechanism for large multi-unit systems and a powerful bottom-up technology for micro/nanofabrication. Controlled self-assembly and dynamic reconfiguration of large ensembles of microscopic particles can effectively bridge these domains to build innovative systems. In this perspective, we present SelfSys, a novel platform for the automated control of the fluidic selfassembly of microparticles. SelfSys centers around a waterfilled microfluidic chamber whose agitation modes, induced by a coupled ultrasonic actuator, drive the assembly. Microparticle dynamics is imaged, tracked and analyzed in real-time by an integrated software framework, which in turn algorithmically controls the agitation modes of the microchamber. The closed control loop is fully automated and can direct the stochastic assembly of microparticle clusters of preset dimension. Control issues specific to SelfSys implementation are discussed, and its potential applications presented. The SelfSys platform embodies at microscale the automated self-assembly control paradigm we first demonstrated in an earlier platform.

Standardised and high-throughput methods have been developed for the production and experimental handling of some 3D in vitro models. However, adapted analytical tools are still missing for scientists and researchers to fully exploit the potential of complex cellular models in pre-clinical drug testing and precision medicine. Histology is the established, cost-effective and gold standard method for structural and functional tissue analysis. However, standard histological processes are challenging and costly to apply to 3D cell models, as their small size often leads to poor alignment of samples, which lowers analysis throughput. This body of work proposes a new approach: HistoBrick facilitates histological processing of spheroids and organoids by enabling gel embedding of 3D cell models with precise coplanar alignment, parallel to the sectioning plane, thus minimising the loss of sample material. HistoBrick’s features are compatible with automation standards, potentially allowing automated sample transfer from a multi-well plate to the gel device. Moreover, HistoBrick’s technology was validated by demonstrating the alignment of HepG2 cultured spheroids measuring 150–200 µm in diameter with a height precision of ± 80 µm. HistoBrick allows up to 96 samples to be studied across minimal sections, paving the way towards high-throughput micro-histology.

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