Unicellular parasites have developed sophisticated swimming mechanisms to survive in a wide range of environments. Cell motility of African trypanosomes, parasites responsible for fatal illness in humans and animals, is crucial both in the insect vector and the mammalian host. Using millisecond-scale imaging in a microfluidics platform along with a custom made optical trap, we are able to confine single cells to study trypanosome motility. From the trapping characteristics of the cells, we determine the propulsion force generated by cells with a single flagellum as well as of dividing trypanosomes with two fully developed flagella. Estimates of the dissipative energy and the power generation of single cells obtained from the motility patterns of the trypanosomes within the optical trap indicate that specific motility characteristics, in addition to locomotion, may be required for antibody clearance. Introducing a steerable second optical trap we could further measure the force, which is generated at the flagellar tip. Differences in the cellular structure of the trypanosomes are correlated with the trapping and motility characteristics and in consequence with their propulsion force, dissipative energy and power generation.

In this review, we give an overview of the current state of microfluidic-based high-throughput drug assays. In this highly interdisciplinary research field, various approaches have been applied to high-throughput drug screening, including microtiter plate, droplets microfluidics as well as continuous flow, diffusion and concentration gradients-based microfluidic drug assays. Therefore, we reviewed over 100 recent publications in the field and sorted them according to their microfluidic approach. As a result, we are showcasing, comparing and discussing broadly applied approaches as well as singular promising ones that might contribute to shaping the future of this field.

In the last three decades, microfluidics and its applications have been on an exponential rise, including approaches to isolate rare cells and diagnose diseases on the single-cell level. The techniques mentioned herein have already had significant impacts in our lives, from in-the-field diagnosis of disease and parasitic infections, through home fertility tests, to uncovering the interactions between SARS-CoV-2 and their host cells. This review gives an overview of the field in general and the most notable developments of the last five years, in three parts: 1. What can we detect? 2. Which detection technologies are used in which setting? 3. How do these techniques work? Finally, this review discusses potentials, shortfalls, and an outlook on future developments, especially in respect to the funding landscape and the field-application of these chips.

We present a single cell viability assay, based on chemical gradient microfluidics in combination with optical micromanipulation. Here, we used this combination to in situ monitor the effects of drugs and chemicals on the motility of the flagellated unicellular parasite Trypanosoma brucei; specifically, the local cell velocity and the mean squared displacement (MSD) of the cell trajectories. With our method, we are able to record in situ cell fixation by glutaraldehyde, and to quantify the critical concentration of 2-deoxy-D-glucose required to completely paralyze trypanosomes. In addition, we detected and quantified the impact on cell propulsion and energy generation at much lower 2-deoxy-D-glucose concentrations. Our microfluidics-based approach advances fast cell-based drug testing in a way that allows us to distinguish cytocidal from cytostatic drug effects, screen effective dosages, and investigate the impact on cell motility of drugs and chemicals. Using suramin, we could reveal the impact of the widely used drug on trypanosomes: suramin lowers trypanosome motility and induces cell-lysis after endocytosis.