3D‐Printed Microinjection Needle Arrays via a Hybrid DLP‐Direct Laser Writing Strategy

Abstract

Microinjection protocols are ubiquitous throughout biomedical fields, with hollow microneedle arrays (MNAs) offering distinctive benefits in both research and clinical settings. Unfortunately, manufacturing‐associated barriers remain a critical impediment to emerging applications that demand high‐density arrays of hollow, high‐aspect‐ratio microneedles. To address such challenges, here, a hybrid additive manufacturing approach that combines digital light processing (DLP) 3D printing with “ex situ direct laser writing (esDLW)” is presented to enable new classes of MNAs for fluidic microinjections. Experimental results for esDLW‐based 3D printing of arrays of high‐aspect‐ratio microneedles—with 30 µm inner diameters, 50 µm outer diameters, and 550 µm heights, and arrayed with 100 µm needle‐to‐needle spacing—directly onto DLP‐printed capillaries reveal uncompromised fluidic integrity at the MNA‐capillary interface during microfluidic cyclic burst‐pressure testing for input pressures in excess of 250 kPa (n = 100 cycles). Ex vivo experiments perform using excised mouse brains reveal that the MNAs not only physically withstand penetration into and retraction from brain tissue but also yield effective and distributed microinjection of surrogate fluids and nanoparticle suspensions directly into the brains. In combination, the results suggest that the presented strategy for fabricating high‐aspect‐ratio, high‐density, hollow MNAs could hold unique promise for biomedical microinjection applications.

Direct laser writing-enabled 3D printing strategies for microfluidic applications

“…The researchers demonstrated their esDLW-printed microneedle arrays by performing fluidic microinjection protocols with: (i) dyed aqueous fluids and suspensions of fluorescently labelled nanoparticles, which were each injected into excised mouse brains (Fig. 8h), 218 and (ii) suspensions of dendritic cells and HEK293 cells. 219 While these strategies involved DLW-printing onto mesoscale fluidic components with a single output portnamely, capillaries with outer diameters ranging from 140 μm to 1 mm-researchers have also reported the ability to DLW-print microfluidic structures directly atop bulk microfluidic systems with externally accessible fluidic ports.…”

“…A critical caveat to the aforementioned reports for DLWprinting millimetre-and submillimetre-scale microfluidic components is that the vast majority of these approaches rely on the use of "Dip-in Laser Lithography (DiLL)" DLW configurations. [202][203][204][205][206][207][208][209][210][211][215][216][217][218][219][221][222][223] In contrast to oil-immersion DLW (Fig. 6), DiLL configurations involve immersing the objective lens directly in the photomaterial (Fig.…”

“…(g) Microfluidic structures with arbitrary geometries esDLW-printed onto fused silica glass capillary tubes and loaded with fluid 217. (h) Hollow microneedle arrays esDLW-printed onto "Digital Light Processing (DLP)" 3D-printed capillaries for injecting fluid into excised mouse brains 218. (i) Hollow conical microneedles esDLW-printed atop a microfluidic chip with external ports (prepared by femtosecond irradiation, annealing, grinding, and polishing) 220.…”

Modern microelectronics and microfluidics on microneedles

“…Microinjection is a scheme to deliver liquid drugs and vaccine preparations (such as DNA, RNA, or micro/nanoparticles) to a single location of interest through hollow MNs (single or array). 95 It is more flexible than solid MNs dissolving or coating liquid preparations (the amounts of drugs delivered can be larger, more sustainable and easier to control), and there is no need to worry about curing and other processes to reduce the preparation (especially vaccine) activity. 73 In addition, it is necessary for many drugs to adopt the scheme because as a liquid dosage form, drugs are dispersed in the medium in the form of molecules or particles, with large dispersion and rapid absorption, which can quickly exert their efficacy and reduce the irritation of some drugs.…”

“…Finally, in vitro experiments using excised mouse brains proved that MNs can not only physically withstand the ability to enter and retract from brain tissues but also effectively and distributively realize the delivery function. 95 Hellmann et al created a microchannel in a polymethyl methacrylate (PMMA) substrate by a laser-induced process and then printed hollow MNs on the opening of the microchannel by direct laser writing (DLW) (Fig. 8B).…”