The in vivo analysis of a small multicellular organism such as the nematode Caenorhabditis elegans, enables fundamental biomedical and environmental studies of a complete organism under normal physiological conditions. Continuous advancements in photonics, electronics, as well as the material sciences, are paving the way towards miniaturized bioanalytical systems, known as labs-on-a-chip (LOC). These microfluidic technologies facilitate the manipulation and study of nematodes in a precise, real-time, portable, and cost-effective manner, potentially for high throughput operation. In this paper we review all currently available "worm-on-a-chip" miniaturized systems that address the manipulation, detection, and study of the sensory response of C. elegans, and take a close look at their advantages, application challenges, and scientific potential. The paper aims to consolidate recent results of dedicated worm microsystems that target a better understanding of C. elegans. Natalia Bakhtina received her diploma in electrical engineering at the department of advanced technologies of radioelectronics, Russian State Technological University named aer K.E. Tsiolkovsky (MATI), Moscow, Russia in 2009. In 2011 she received her MSc degree in microsystems engineering from the Hochschule Furtwangen University of Applied Sciences, Germany. Since 2012, she is a PhD candidate at the Department of Microsystems Engineering (IMTEK) of the University of Freiburg, focusing on the detection and immobilization of C. elegans.

Continuous development of fabrication technologies, such as two-photon polymerization (2PP), allows the exact reconstruction of specifi c volume shapes at micro-and nanometer precision. Advancements in the engineering of new materials, such as ionic liquids (ILs), are bringing superior advantages in terms of material characteristics, facilitating a combination of optical and electrical properties, as well as lithographic capabilities. In this paper, 2PP is utilized for structuring of a novel IL-polymer composite in a single-step manufacturing process with high resolution, down to 200 nm, and high aspect ratio, up to 1:20. The composition, based on a photosensitive photoresist (e.g., IP-L 780 or SU-8) and the IL 1-butyl-3-methylimidazolium dicyanamide, possesses a good ionic conductivity (in the range of 1-10 mS cm −1 ) over a wide frequency bandwidth (1 kHz-1 MHz), an electrochemical window of 2.7 V, and a good optical transparency (transmission value of 90% for a 170 µm thick fi lm). The fabricated structures are characterized and the phenomenon of enhanced conductivity (up to 4 S cm −1 ) is explained. Two potential applications, including temperature and relative humidity sensing, are demonstrated as examples. The results suggest a new advanced approach for material structuring that can be regarded as highly most promising for a wide range of applications.

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The development of in vitro models, which accurately recapitulate early embryonic development, is one of the fundamental challenges in stem cell research. Most of the currently employed approaches involve the culture of embryonic stem cells (ESCs) on 2D surfaces. However, the monolayer nature of these cultures does not permit cells to grow and proliferate in realistic 3D microenvironments, as in an early embryo. In this paper, novel 3D synthetic microstructure arrays, fabricated by two-photon polymerization photolithography, are utilized to mimic tissue-specific architecture, enabling cell-to-matrix interaction and cell-to-cell communication in vitro. Mouse ESCs (mESCs) are able to grow and proliferate on these structures and maintain their pluripotent state. Furthermore, the 3D microstructure arrays are integrated into a microscopy slide allowing the evaluation of the expression of key pluripotency factors at the single cell level. Comparing 2D and 3D surfaces, mESCs grown in serum + leukemia inhibitory factor on 3D microstructures exhibit a stronger signal intensity of three pluripotency markershomeobox protein NANOG, octamer-binding transcription factor 4, and estrogen-related receptor beta (ESRRB)-and more homogenous expression of NANOG and ESRRB, than cells cultivated in 2i medium, demonstrating that 3D microstructures capture naïve pluripotency in vitro. Thus, the slide affords a novel and unique tool to model and study early development.

A novel ionic liquid–polymer composite material is reported by J. G. Korvink and co‐workers on page 1683, alongside an approach for its patterning by two‐photon nanolithography. The unique properties of the material are combined with a single‐step process for its 3D structuring, having nanometer resolution and high aspect ratio. A proof‐of‐concept multifunctional sensor for temperature and relative humidity sensing is demonstrated.