Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2024 Mar 13.
Published in final edited form as: Proc IEEE Int Conf Micro Electro Mech Syst. 2024 Feb 22;2024:1174–1177. doi: 10.1109/mems58180.2024.10439296

A 3D-MICROPRINTED COAXIAL NOZZLE FOR FABRICATING LONG, FLEXIBLE MICROFLUIDIC TUBING

Olivia M Young 1, Bailey M Felix 2, Mark D Fuge 1, Axel Krieger 3, Ryan D Sochol 1,2
PMCID: PMC10936740  NIHMSID: NIHMS1973069  PMID: 38482160

Abstract

A variety of emerging applications, particularly those in medical and soft robotics fields, are predicated on the ability to fabricate long, flexible meso/microfluidic tubing with high customization. To address this need, here we present a hybrid additive manufacturing (or “three-dimensional (3D) printing”) strategy that involves three key steps: (i) using the “Vat Photopolymerization (VPP) technique, “Liquid-Crystal Display (LCD)” 3D printing to print a bulk microfluidic device with three inlets and three concentric outlets; (ii) using “Two-Photon Direct Laser Writing (DLW)” to 3D microprint a coaxial nozzle directly atop the concentric outlets of the bulk microdevice, and then (iii) extruding paraffin oil and a liquid-phase photocurable resin through the coaxial nozzle and into a polydimethylsiloxane (PDMS) channel for UV exposure, ultimately producing the desired tubing. In addition to fabricating the resulting tubing—composed of polymerized photomaterial—at arbitrary lengths (e.g., > 10 cm), the distinct input pressures can be adjusted to tune the inner diameter (ID) and outer diameter (OD) of the fabricated tubing. For example, experimental results revealed that increasing the driving pressure of the liquid-phase photomaterial from 50 kPa to 100 kPa led to fluidic tubing with IDs and ODs of 291±99 μm and 546±76 μm up to 741±31 μm and 888±39 μm, respectively. Furthermore, preliminary results for DLW-printing a microfluidic “M” structure directly atop the tubing suggest that the tubing could be used for “ex situ DLW (esDLW)” fabrication, which would further enhance the utility of the tubing.

Keywords: Additive Manufacturing, Two-Photon Polymerization, 3D Printing, Direct Laser Writing, Microfluidics, Tubing

INTRODUCTION

An increasing number of biomedical applications— particularly in the area of minimally invasive surgery [1]— rely on long, flexible micro/mesofluidic tubing, ranging from steerable microcatheters for endovascular interventions [2–4] to soft microrobotic tissue biopsy tools [3–9]. Furthermore, esDLW protocols for 3D printing microfluidic structures atop such tubing can greatly enhance the capabilities of these systems [8–12]. This capability is facilitated by the submicron resolution of two-photon polymerization and the ability to fabricate structures with geometries not possible with other manufacturing methods [13–15]. Unfortunately, methods to fabricate custom tubing for such applications remain limited, leading researchers to seek undesirable pathways, such as gluing capillaries together or gluing microfluidic components to commercial products [16,17]. These processes require manual alignment steps that can make repeatability difficult and dependent on user skill. Previously, researchers used DLW to 3D microprint coaxial nozzles that harnessed a shear fluid to create solid, silk microfibers [18], DLW-printed nozzles for micro-droplet generation [17], as well as several DLW-printed gas dynamic virtual nozzles [19–21]. For a different application, our group has previously shown the ability to esDLW microfluidic structures directly only additively manufactured microfluidic chips [22]. In this work, we combine and extend these approaches by leveraging esDLW to 3D microprint coaxial nozzles directly atop a 3D-printed microfluidic device, which can then be used to produce custom microfluidic tubing of arbitrary lengths.

MATERIALS AND METHODS

Concept

Here we present a novel approach for fabricating long, flexible tubing by means of 3D printing, microfluidics, and photopolymerization (Fig. 1). First, a microfluidic device with three inlets and three concentric outlets is fabricated via “liquid-crystal display (LCD)” 3D printing (Fig. 1a). Next, a coaxial nozzle is esDLW-printed directly atop the LCD-printed microdevice (Fig. 1b). Following development, fluidic couplers are inserted into the inlets while a PDMS channel is attached to the outlet over the nozzle (Fig. 1c). To fabricate the microfluidic tubing, paraffin oil is loaded into the outer and inner channels while a liquid-phase photocurable resin is loaded into the middle channel, and then the fluids flowing into the PDMS channel are exposed to UV light to photopolymerize the resin (Fig. 1d). After development (infusing IPA and post curing), the tubing can be loaded into a DLW 3D printer for subsequent esDLW protocols (Fig. 1e).

Figure 1:

Figure 1:

Open in a new tab

Conceptual illustrations of the presented strategy for fabricating long, flexible microfluidic tubing via a 3D-microprinted nozzle. (a) “Liquid-crystal display (LCD)” 3D printing of a microfluidic device with three inlets and three concentric outlets perpendicular to the surface of the inlets. (b) The “ex situ Direct Laser Writing (esDLW)” printing process for the nozzle 3D microprinting. (c) Metal fluidic couplers and PDMS channel interfaced with the LCD-DLW-printed nozzle device. (d) Microfluidic tubing fabrication. (e) An “M” microstructure esDLW-printed onto the tubing.

Liquid Crystal Display (LCD)-Based 3D Printing of the Microfluidic Device

The microfluidic device was designed with three inlets and three concentric outlets to allow for the necessary flow of material for tubing fabrication. The microfluidic device was also designed to easily fit into the DLW 3D printer. The microfluidic device was designed using the computer aided design (CAD) software, SolidWorks (Dassault Systèmes, France), exported as an STL, and imported into the computer aided manufacturing (CAM) software, Chitubox (Chitubox, Shenzhen, China) to generate the LCD printing file. The microfluidic device was printed on the Elegoo Mars 3 (Elegoo, Shenzhen, China) using the CADworks3D Clear Microfluidic Resin (CADworks3D, Ontario, Canada). Following the printing process the microfluidic device was rinsed with isopropyl alcohol (IPA) and the interior channels were flushed with IPA before drying the device with N2 gas. Finally, the microfluidic device was exposed to 405 nm UV light for a 60 second post cure.

Ex Situ Direct Laser Writing (esDLW)-Based 3D Microprinting of the Coaxial Nozzle

The coaxial nozzle was designed using SolidWorks CAD software, exported into the CAM software Describe (Nanoscribe GmbH, Karlsruhe, Germany) to generate the DLW laser writing path. The photoresist IP-Q (Nanoscribe) was dispensed atop the concentric outlets of the microfluidic device. The microfluidic device was loaded into the Nanoscribe Photonic Professional GT2 DLW system in the Dip-in Laser Lithography (DiLL) mode configuration with the 10× objective lens. The coaxial nozzle was printed directly atop of the microfluidic device and aligned to the concentric outputs. To ensure a complete fluidic seal between the nozzle and the microfluidic device the interface of the microfluidic device was found manually, and the print was started with a 30 μm overlap between the base of the nozzle and the microfluidic device. Following the esDLW printing process the input channels of the microfluidic device were filled with propylene glycol methyl ether acetate (PGMEA) and the coaxial nozzle was submerged in PGMEA for 30 minutes. Then the input channels were flushed with PGMEA before allowing the coaxial nozzle to be submerged in PGMEA for an additional 30 minutes. The coaxial nozzle and microfluidic device were then rinsed with IPA to remove any uncured photoresist and dried with N2 gas.

Microfluidic Tubing Fabrication

A Polydimethylsiloxane (PDMS) channel with a diameter of 1.75 mm was attached to the microfluidic device over the concentric outlets and the coaxial nozzle. Fluids were loaded into the microfluidic device using fluorinate ethylene propylene fluidic tubing (Cole-Parmer, Vernon Hills, IL) and stainless-steel catheter couplers (20 ga., Instech, Plymouth Meeting, PA). Paraffin oil (MilliporeSigma, St. Louis, MO) was loaded into the outer and inner channels of the microfluidic device at 100 kPa to act as a sheathing fluid. The center channel was loaded with the photomaterial (50% monocure3D flex100, 50% 3D rapid tuff, Monocure3D, Sydney, Australia) at pressures ranging from 50 kPa to 100 kPa in 10 kPa intervals. Pressures were applied to the microfluidic device and coaxial nozzle using the Fluigent Microfluidic Control System MFCS and OxyGEN software (Fluigent, France). The paraffin oil and photomaterial were exposed to a ring of UV light at 405 nm while flowing through the PDMS channel to polymerize the photomaterial. The tubing was then flushed with IPA and exposed to 405 nm light for a 30 second post cure.

esDLW-Microprinting atop the Microfluidic Tubing

Following the post-cure, the tubing was loaded into a custom holder and the photoresist IP-Q (Nanoscribe) was dispensed atop the tubing. The tubing was then loaded into the Nanoscribe Photonic Professional GT2 DLW system in the Dip-in Laser Lithography (DiLL) mode configuration with the 10× objective lens. An “M” microstructure with an internal channel was esDLW printed directly atop the microfluidic tubing. Following the esDLW printing process the “M” microstructure was developed in PGMEA for 20 minutes, rinsed with IPA, and dried with N2 gas.

Optical characterization

Scanning electron microscope (SEM) images of fabrication results were performed using a TM4000 Tabletop SEM (Hitachi, Tokyo, Japan).

RESULTS

Microfluidic Device and Coaxial Nozzle Fabrication

Fabrication results for the LCD 3D-printed microdevice and the esDLW-printed coaxial nozzle are presented in Figure 2. The microfluidic device was successfully printed with three independent channels with concentric outlets. The inner diameters (IDs) of the outlets are 350 μm, 800 μm, and 2 mm (Fig. 2a). It should be noted that alternative VPP or potentially “material jetting” 3D printing approaches [23–25] could be similarly employed for fabrication of the bulk microfluidic system. CAM simulations and the corresponding micrographs of the esDLW process for printing the coaxial nozzle atop the microfluidic device are shown in Figure 2b. The esDLW printing process for the coaxial nozzle was completed in approximately 8.5 minutes. SEM micrographs of the coaxial nozzle (Fig. 2c) showed effective alignment of the nozzle with the concentric outlets. The coaxial nozzle has an inner diameter of 100 μm for the center nozzle and an inner diameter of 360 μm for the outer nozzle. The SEM micrographs also showed an effective seal between the esDLW printed nozzle and the microfluidic device.

Figure 2:

Figure 2:

Open in a new tab

Fabrication results. (a) The LCD-printed microfluidic device. Scale bars = 10 mm, 500 μm. (b) Simulations (Top) and corresponding micrographs (Bottom) of the esDLW process for 3D microprinting the nozzle directly onto the outlets of the microfluidic device. Scale bar = 250 μm. (c) SEM micrograph of print results. Scale bar = 500 μm.

Microfluidic Tubing results

To investigate the influence of the input pressure for the photomaterial on the microfluidic tubing ID and OD, we varied the photomaterial input pressure from 50 kPa to 100 kPa in 10 kPa increments while maintaining the input pressure for the paraffin oil loaded into the outer and inner channels at 100 kPa. The experimental setup (including the UV light for curing the tubing) is presented in Figure 3a. Experimental results revealed that increasing the pressure of the photomaterial led to significant increases in the sizes of both the IDs and ODs for the microfluidic tubing. SEM micrographs of tubing with increasing photomaterial pressures are shown in Figure 3b–g. The average IDs ranged from 290.9 μm for 50 kPa to 741.4 μm for 100 kPa, and the average ODs ranged from 546 μm for 50 kPa to 887.9 μm for 100 kPa (Fig. 3h,i). These were statistically significant increases in both ID and OD as the photomaterial pressure increased. In addition, the microfluidic tubing demonstrated effective flexibility following a flush with IPA and post cure. The tubing had a bending angle over 90° (Fig. 4a). Lastly, we examined the compatibility of the microfluidic tubing with esDLW 3D printing. Preliminary fabrication results for esDLW-printing an “M” microstructure with an internal microchannel revealed successful fabrication directly atop the microfluidic tubing (i.e., without photomaterial burning/bubbling-associated failures) (Fig. 4b).

Figure 3:

Figure 3:

Open in a new tab

Microfluidic tubing fabrication results. (a) Images captured from video of tubing UV photocuring production. (b–g) Representative tubing cross sections corresponding to photomaterial input pressures (PPM) of: (b) 50, (c) 60, (d) 70, (e) 80, (f) 90, and (g) 100 kPa. Scale bars = 250 μm. (h,i) Quantified results for tubing (h) inner diameter and (c) outer diameter vs. PPM (all parafilm oil pressures = 100 kPa). * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001

Figure 4:

Figure 4:

Open in a new tab

Results for tubing flexibility and esDLW compatibility. (a) Images captured during a tube bending investigation. (b) SEM micrograph of an “M” microstructure esDLW-printed directly atop the fabricated tubing. Scale bar = 500 μm

CONCLUSIONS

In this work, we presented and demonstrated a novel strategy for fabricating long (i.e., > 10 cm), flexible fluidic tubing with ODs smaller than 1 mm and tunable IDs—i.e., based on varying the distinct input pressures. These results provide an important proof of concept for this fabrication strategy as well as its potential for esDLW compatibility. Future efforts should focus on investigating the microfluidic efficacy for 3D microstructures with internal microchannels esDLW-printed atop the tubing. Another capability of interest is the potential for this approach to be extended to realize long, flexible, multi-lumen tubing, such as by altering the geometry of the coaxial nozzle and the experimental set up. The ability to fabricate multilumen tubing in particular would offer distinctive benefits that could, in turn, drive new applications in soft microrobotics and biomedical fields.

ACKNOWLEDGEMENTS

The authors greatly appreciate the contributions of the members of Bioinspired Advanced Manufacturing (BAM) Laboratory and Terrapin Works staff at the University of Maryland, College Park. This work was supported in part by U.S. National Institutes of Health Award Number 1R01EB033354, U.S. National Science Foundation Award Number 1943356, and the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE2236417. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

REFERENCES

  • [1].Runciman M, Darzi A, and Mylonas GP, “Soft Robotics in Minimally Invasive Surgery,” SoRo, vol. 6, no. 4, pp. 423–443, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Gopesh T et al. , “Soft Robotic Steerable Microcatheter for the Endovascular Treatment of Cerebral Disorders”, Sci. Robot, vol. 6, no. 57, pp. eabf0601, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Li M et al. , “VINE Catheter for Endovascular Surgery,” IEEE Transactions on Medical Robotics and Bionics, vol. 3, no. 2, pp. 384–391, 2021. [Google Scholar]
  • [4].Greer JD et al. , “A Soft, Steerable Continuum Robot That Grows via Tip Extension,” SoRo, vol. 6, no. 1, pp. 95–108, 2019. [DOI] [PubMed] [Google Scholar]
  • [5].McCandless M et al. , “A Soft Robot for Peripheral Lung Cancer Diagnosis and Therapy,” SoRo, vol. 9, no. 4, pp. 754–766, 2022. [DOI] [PubMed] [Google Scholar]
  • [6].Van Lewen D et al. , “A Millimeter-Scale Soft Robot for Tissue Biopsy Procedures,” Adv. Intell. Syst, vol. 5, no. 5, p. 2200326, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Rogatinsky J et al. , “A multifunctional soft robot for cardiac interventions,” Sci. Adv, vol. 9, no. 43, p. eadi5559, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Barbot A et al. , “Liquid Seal for Compact Micropiston Actuation at the Capillary Tip”, Sci. Adv, vol. 6, no. 22, pp. eaba5660, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Power M et al. , “Bistable, Pneumatically Actuated Microgripper Fabricated Using Two-Photon Polymerization and Oxygen Plasma Etching”, Adv. Intell. Syst, vol. 5, no. 4, pp. 2200121, 2023. [Google Scholar]
  • [10].Sarker S et al. , “3D-Printed Microinjection Needle Arrays via a Hybrid DLP-Direct Laser Writing Strategy”, Adv. Mater. Technol, vol. 8, no. 5, pp. 220164, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Acevedo R et al. , “3D Nanoprinted External Microfluidic Structures via Ex Situ Direct Laser Writing”, in 2021 IEEE 34th International Conference on Micro Electro Mechanical Systems (MEMS), Virtual, January 25–29, pp. 10–13, 2021. [Google Scholar]
  • [12].Sarker S et al. , “A Hybrid 3D Micro-Nanoprinting Approach for Biomedical Microinjection Needle Arrays,” in Proceedings of the 20th Solid-State Sensors, Actuators and Microsystems Workshop (Hilton Head 2022), Hilton Head Island, SC, USA, June 5–9, 2022. [Google Scholar]
  • [13].Hahn V et al. , “Rapid Assembly of Small Materials Building Blocks (Voxels) into Large Functional 3D Metamaterials,” Adv. Funct. Mater, vol. 30, no. 26, pp. 1907795, 2020. [Google Scholar]
  • [14].Lamont A et al. , “A facile multi-material direct laser writing strategy,” Lab Chip, vol. 19, pp. 2340–2345, 2019. [DOI] [PubMed] [Google Scholar]
  • [15].Alsharhan A et al. , “3D microfluidics via cyclic olefin polymer-based in-situ direct laser writing,” Lab Chip, vol. 19, pp. 2799–2810, 2019. [DOI] [PubMed] [Google Scholar]
  • [16].Barbot A et al. , “Microfluidics at Fiber Tip for Nanoliter Delivery and Sampling”, Adv. Sci, vol. 8, no. 10, pp. 2004643, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Dewandre A et al. , “Microfluidic Droplet Generatin Based on Non-Embedded Co-Flow-Focusing Using 3D Printed Nozzle”, Sci. Rep, vol. 10, pp. 21616, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Lüken A, et al. , “Biocompatible Micron-Scale Silk Fibers Fabricated by Microfluidic Wet Spinning”, Adv. Healthc. Mater, vol. 10, no. 20, 2100898, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Knoška J et al. , “Ultracompact 3D Microfluidics for Time-Resolved Structural Biology”, Nat. Commun, vol. 11, pp. 657, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Nelson G, et al. , “Three-dimensional-printed gas dynamic virtual nozzles for x-ray laser sample delivery,” Opt. Express, vol. 24, pp. 11515–11530, 2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Wiedorn M, et al. , “Megahertz serial crystallography,” Nat. Commun, vol. 9, pp. 4025, 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Young O et al. , “3D Microprinting of Multi-Actuator Soft Robots onto 3D-Printed Microfluidic Devices via Ex Situ Direct Laser Writing,” in Proceedings of the 20th Solid-State Sensors, Actuators and Microsystems Workshop (Hilton Head 2022), Hilton Head Island, SC, USA, June 5–9, 2022. [Google Scholar]
  • [23].Sochol R et al. , “3D printed microfluidic circuitry via multijet-based additive manufacturing,” Lab Chip, vol. 16, pp. 668–678, 2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Hubbard J et al. , “Fully 3D-printed soft robots with integrated fluidic circuitry,” Sci. Adv, vol. 7, pp. eabe5257, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Hayes B, Hainsworth T, and MacCurdy R, “Liquid solid co-printing of multi-material 3D fluidic devices via material jetting,” Addit. Manuf, vol. 55, pp. 102785, 2022. [Google Scholar]

RESOURCES