3D-printed miniaturized fluidic tools in chemistry and biology

Abstract

3D printing (3DP), an additive manufacturing (AM) approach allowing for rapid prototyping and decentralized fabrication on-demand, has become a common method for creating parts or whole devices. The wide scope of the AM extends from organized sectors of construction, ornament, medical, and R&D industries to individual explorers attributed to the low cost, high quality printers along with revolutionary tools and polymers. While progress is being made but big manufacturing challenges are still there. Considering the quickly shifting narrative towards miniaturized analytical systems (MAS) we focus on the development/rapid prototyping and manufacturing of MAS with 3DP, and application dependent challenges in engineering designs and choice of the polymeric materials and provide an exhaustive background to the applications of 3DP in biology and chemistry. This will allow readers to perceive the most important features of AM in creating (i) various individual and modular components, and (ii) complete integrated tools.

Keywords: 3D printing; Additive manufacturing; DLP; FDM; Lab-on-a-chip; Microfluidics; MultiJet; SLA; SLS.

Fig. 1.

Analytics of how research in 3DP has increased over a decade. In 2016 global 3DP healthcare market share was USD 170 million which is growing at 20% CAGR.

Fig. 2.

Illustration of common challenges faced with 3D printing tools. Printing fluidic networks on a single device using FDM technology usually result in reagent leakage as shown in (a)24. Carefully choosing a polymeric material is very crucial as variants of same material from different vendors may result in significant structural differences as visible in (b)27. Ultimaker Transparent, Ultimaker Translucent, Innofil, and InnoPET were employed to print optically clear cuvettes demonstrating this variation against a standard PMMA cuvette (adapted from ref [37] with permission). In (c & d) the SEM image shows effective replication of structural inaccuracies on the 3D-printed molds (c) on the PDMS casts (d).

Fig. 3.

Illustrates the workflow associated to print PDMS with filament extrusion using a modified syringe-based extrusion head.

Fig. 4.. (a)

Illustrates a summary of different approaches for 3D printing with their print qualities. Binder Jetting: BJ; Electron Deposition Modeling: EDP; Fused Deposition Modeling: FDM; Hybrid Process: HP; Laser Melting: LM; Laser Sintering; Material Jetting: MJ; Photopolymer Jetting: PJ; Stereolithography: SL. (b) An overview of 3 dimensional light projection scheme in Holographic 3D printing set up (i) while in panel (ii) actual light projections of squares can be seen from all three planes that will create a hollow cube as depicted in a single projection of light as shown in panel (iii), a video related to this technology can be find at (https://www.youtube.com/watch?v=00H-hXufpQE). (c) Depicts Continuous Liquid Interface Production scheme, which uses a combination of oxygen-based quenching of the reactive photoinitiator, allowing rapid printing within few minutes (15–20 min). (d) A set up of recently developed UDP method by Uniz Technologies, which is basically the fastest 3D printer in all segments. This is an arrangement of peeling in only z-direction by introducing a cooling coil in the otherwise non-sticky resin vat. The cooling causes peeling of the cured parts which also minimizes polymer shrinking due to hot-cold cycles.

Fig. 5.

a. Minihydrocyclone for cell separation and concentration. Basic components in designing an efficient concentrator are diameters of inlet D₀, Inlet diameter (Di), inlet overlap length (h), Length of the concentrator cylinder (L), and outlet diameter (Do) which controls the Feed and overflow for size-dependent focusing of cells as depicted in the bottom panel of ‘a’ [166]. Adapted from ref . Copyright (2017) The Royal Society of Chemistry. b. illustrates cell sorting and capturing at single cell level. Cells were exposed to fluidic sheer at the opening thus yeast buds cleaved, which authors have used for studying genetic makeup and growth physiology [167]. Adapted with permission from ref. . Copyright (2014) American Chemical Society. c. Illustration of highly integrated chip with on-chip valves (i) that can be manipulated on demand via appropriate airflow in the channel underneath of the fluidic channel (ii, iii). The complex functioning of on-chip integration was successfully demonstrated by culturing CHO cells that also has gradient generator on-board [168]. Reproduced from Ref. with permission from The Royal Society of Chemistry.

Fig. 6.

3D-printed tools to perform ECL (I, III) and CL (II) for detecting prostate cancer-specific panel of biomarkers. I. FDM printed motor-free device with integrated reagent reservoirs, supercapacitor driven pumps, and electrodes. Reprinted from ref . Copyright (2016), with permission from Elsevier. II. SLA printed transparent single body chip with integrated mixers. Reproduced from Ref. with permission from The Royal Society of Chemistry. III. SLA printed transparent chip with integrated three electrode system on-chip for biomarker detection. Reprinted from ref. . Copyright (2017) American Chemical Society.

Fig. 7.

Modular valves (a, b) and pumps (c, d) are part of a bigger design challenge. These modules were combined together, and an integrated device was fabricated. The performance of the individual modules and the tool was demonstrated by detecting urinary total protein using colorimetric approach. Adapted with permission from ref. . Copyright (2016) American Chemical Society.