Microfluidics-enabled phenotyping, imaging, and screening of multicellular organisms

Abstract

This paper reviews the technologies that have been invented in the last few years on high-throughput phenotyping, imaging, screening, and related techniques using microfluidics. The review focuses on the technical challenges and how microfluidics can help to solve these existing problems, specifically discussing the applications of microfluidics to multicellular model organisms. The challenges facing this field include handling multicellular organisms in an efficient manner, controlling the microenvironment and precise manipulation of the local conditions to allow the phenotyping, screening, and imaging of the small animals. Not only does microfluidics have the proper length scale for manipulating these biological entities, but automation has also been demonstrated with these systems, and more importantly the ability to deliver stimuli or alter biophysical/biochemical conditions to the biological entities with good spatial and temporal controls. In addition, integration with and interfacing to other hardware/software allows quantitative approaches. We include several successful examples of microfluidics solving these high-throughput problems. The paper also highlights other applications that can be developed in the future.

Agarose hydrogel microcompartments for imaging sleep- and wake-like behavior and nervous system development in Caenorhabditis elegans larvae

“…In the recent past microfluidic devices have been developed to facilitate the study of C. elegans and other small multicellular organisms (Chronis, 2010;Crane et al, 2010). C. elegans has been kept and imaged inside microcompartments for several days.…”

Amplitude-modulated sinusoidal microchannels for observing adaptability in C. elegans locomotion

“…The shape and speed of undulations depend on the response of the C. elegans to the physical environmentthey crawl on agarose surface with undulations of low frequency and smaller wavelength; they swim in M9 buffer with undulations of higher frequency and longer wavelength. 7,11 With advances in microfluidic technology, 12 a new class of worm assays ͑T-mazes for memory and learning, 13 culture and detection chambers, 3,5 micro-clamps for olfactory sensing, 14 integrated microscopy system for rapid phenotyping, 15 piezoresistive displacement clamps for force measurement, 16 compact disks for geotaxis studies, 17 micro-traps for nanosurgery, 18 and screening and sorting devices [19][20][21] ͒ have emerged to study the mechanics and neuromuscular functioning of C. elegans. Particularly relevant to this work are microfluidic devices 8,9,22,23 that allow the observation of C. elegans locomotion in soil-like environments ͑compared to that on planar surfaces 7,11 ͒.…”

Microfluidic Platform for the Study of Caenorhabditis elegans

“…324 W. Shi et al Advances in the application of microfluidics technology to biological assays help to automate otherwise time-consuming experiments. In recent years, microfluidics technology is emerging as an attractive and enabling platform for the study of C. elegans, including their behavior and neurobiology [10][11][12][13][14][15][16][17]. The unique properties of this technology lie in several aspects: first, the dimension of microfluidic channel is a perfect match with the size of the tiny worm.…”