No abstract

Single-cell screening is used to sort a stream of cells into clusters (or types) based on pre-specified biomarkers, thus supporting type-driven biochemical analysis. Reconfigurable flowbased microfluidic biochips (RFBs) can be utilized to screen hundreds of heterogeneous cells within a few minutes, but they are overburdened with the control of a large number of valves. To address this problem, we present a pin-constrained RFB design methodology for single-cell screening. The proposed design is analyzed using computational fluid dynamics simulations, mapped to an RC-lumped model, and combined with intervalve connectivity information to construct a high-level synthesis framework, referred to as Sortex. Simulation results show that Sortex significantly reduces the number of control pins and fulfills the timing requirements of single-cell screening.

The development of a planar manipulator with flexure joints and redundant actuation has been considered before, showing that the redundancy can be exploited to increase the support stiffness and to reduce static actuator loads. In this previous design the manipulator’s workspace has been defined to encompass all kinematically accessible end effector positions. In the current paper we reconsider the design philosophy. It will be shown that limiting the workspace (“less”) ultimately results in a better performance in a larger area (“more”).The dynamic performance of the manipulator is evaluated with a flexible multibody model. The links can safely be considered as rigid parts, but the model has to account for the nonlinear stiffness behaviour of the flexure joints undergoing relatively large deflections. The nonlinear spatial flexible beam elements implemented in the spacar software result in numerically efficient models that have proven to be well-suited for design optimisation. With such a flexible multibody model, the geometry of the manipulator is optimised to maximise the workspace area while assuring a minimal parasitic natural frequency and limiting the local stresses throughout the full workspace. Furthermore, the simulations show that preloading of the flexure joints results in reduced actuator torques that are needed to counteract the finite joint compliance for stationary positioning anywhere except for the equilibrium position of the end effector.The optimised design has been build and validated experimentally. A control system that handles the actuator redundancy by minimising the 2-norm of the driving torques has been synthesised. It is demonstrated that the setup’s behaviour is similar to the model and that in particular the preloading significantly lowers the required actuator torques.

The development of a compliant (or flexure-based) manipulator with redundant actuation has been considered before, showing that the redundancy can be exploited to increase the support stiffness and reduce actuator loads. In this previous design the manipulator's workspace has been defined to encompass all kinematically accessible end effector positions. In this paper we reconsider the design philosophy. It appears that limiting the workspace ("less") ultimately results in a better performance in a larger area ("more") as before.The dynamic performance of the manipulator is evaluated with a flexible multibody model. The links are assumed to be rigid. The SPACAR software is used as its flexible beam element can describe the non-linear behaviour of the flexure joints well at rather large deflections. This numerically efficient model is well-suited for design optimisation which aims at the largest workspace area while assuring a minimal parasitic natural frequency and limiting the local stresses throughout the full workspace. Furthermore, the simulations show that preloading of the flexures results in smaller required actuator torques.An optimised design has been build. A control system has been synthesised that handles the actuator redundancy by minimising the 2-norm of the driving torques. It is demonstrated that the setup's behaviour is similar to the model and that in particular the preloading significantly lowers the required actuator torques.

Flow-based microfluidic biochips can be used to perform bioassays by manipulating a large number of on-chip valves. These biochips are increasingly used today for biomolecular recognition, single-cell screening, and point-of-care disease diagnostics, and design-automation solutions for flow-based microfluidics enable the mapping and optimization of bimolecular protocols and software-based valve control. However, a key problem that has not received adequate attention is chip-to-world interfacing, which requires the use of off-chip control equipment to provide control signals for the on-chip valves. This problem is exacerbated by the increase in the number of valves as chips get more complex. To address the interfacing problem, we present an efficient pin-count minimization (synthesis) problem, referred to as Synterface, which uses on-chip microfluidic logic gates and optimization based on concepts from linear algebra. We present results to show that Synterface significantly reduces pin-count and simplifies the external interface for flow-based microfluidics.