Citation: Kutscher, A.; Kalenczuk, P.; Shahadha, M.; Grünzner, S.; Obst, F.; Gruner, D.; Paschew, G.; Beck, A.; Howitz, S.; Richter, A. Fabrication of Chemofluidic Integrated Circuits by Multi-Material Printing. Micromachines 2023, 14, 699. https://doi.org/10.3390/mi14030699 Academic Editor: Laura Cerqueira Received: 2 March 2023 Revised: 15 March 2023 Accepted: 18 March 2023 Published: 22 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). micromachines Article Fabrication of Chemofluidic Integrated Circuits by Multi-Material Printing Alexander Kutscher 1 , Paula Kalenczuk 1 , Mohammed Shahadha 1 , Stefan Grünzner 1 , Franziska Obst 1 , Denise Gruner 1,2 , Georgi Paschew 1 , Anthony Beck 1 , Steffen Howitz 3 and Andreas Richter 1, * 1 Institute of Semiconductors and Microsystems, Technische Universität Dresden, 01062 Dresden, Germany 2 Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Fetscherstr. 74, 01307 Dresden, Germany 3 GeSiM—Gesellschaft für Silizium-Mikrosysteme mbH, Bautzner Landstrasse 45, D-01454 Radeberg, Germany * Correspondence: andreas.richter7@tu-dresden.de Abstract: Photolithographic patterning of components and integrated circuits based on active poly- mers for microfluidics is challenging and not always efficient on a laboratory scale using the traditional mask-based fabrication procedures. Here, we present an alternative manufacturing process based on multi-material 3D printing that can be used to print various active polymers in microfluidic structures that act as microvalves on large-area substrates efficiently in terms of processing time and consumption of active materials with a single machine. Based on the examples of two chemofluidic valve types, hydrogel-based closing valves and PEG-based opening valves, the respective printing procedures, essential influencing variables and special features are discussed, and the components are characterized with regard to their properties and tolerances. The functionality of the concept is demonstrated by a specific chemofluidic chip which automates an analysis procedure typical of clinical chemistry and laboratory medicine. Multi-material 3D printing allows active-material devices to be produced on chip substrates with tolerances comparable to photolithography but is faster and very flexible for small quantities of up to about 50 chips. Keywords: chemofluidics; microfluidics; hydrogel; PEG; closing and opening valve; printing 1. Introduction One of the central success factors of microelectronic circuit technology is the coupling of the number of active chip components and thus of circuit functionality due to improve- ments in manufacturing technologies [1]. Layer structuring processes play a key role as they are beneficial to manufacture all important functional structures including metallic conductor paths, dielectrics and also the electronic semiconductor components by stacking structured material layers. Modern microelectronic circuits with billions of transistors go through several hundred sequential layer structuring processes, with pattern transfer almost exclusively by photolithography. It is natural to apply the economy of scale of a circuit technology to the diverse applications of microfluidics [2,3]. However, although now mature and economically successful, lab-on-a-chip (LoC) achievements to date have hardly been based on circuit scaling. In the few commercial large-scale integrated (LSI) LoC, for example, from Fluidigm, photolithographic layer structuring processes play a major but not scaling role. The most important reason for this is probably the lack of a universal component such as the microfluidic transistor, on which an economy of scale can be based [4]. Logical microfluidics [5,6] addresses this issue with its two manifestations: pressure-controlled logical micropneumatics with membrane-based switching elements, and chemofluidics. The latter differs from the other LoC platforms in that it is not con- trolled electronically but directly by the process chemistry on the chip and is based on active-material devices, which are also to be integrated into the chip by layer-structuring processes [7–9]. Already in the first reports, LSI circuits with active-material components Micromachines 2023, 14, 699. https://doi.org/10.3390/mi14030699 https://www.mdpi.com/journal/micromachines