Microneedles in Advanced Microfluidic Systems: A Systematic Review throughout Lab and Organ-on-a-Chip Applications

Abstract

Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms.

Modern microelectronics and microfluidics on microneedles

“…To date, numerous reviews on MNs have been reported from various aspects. [11][12][13][14][15] However, a comprehensive and detailed review on the integration of MNs with microelectronics or microfluidics, especially with both of them, has yet to be introduced. Therefore, in this review, we introduced the material, shape, patterns and manufacturing methods of MNs in integrated systems.…”

“…48,49 Polydimethylsiloxane (PDMS), a polymer characterized by a polysiloxane backbone, is widely used to make MNs and their substrates, which also include microfluidic and microelectronic structures, because of its stable chemical properties, good thermal stability, transparency and biocompatibility, especially its extensibility and flexibility (it can meet specific needs through various surface modifications). 15,[50][51][52] Chitosan (CS) is a unique alkaline polysaccharide from arthropod chitin, whose extraction process is simple, non-toxic, mild and non-irritating. It has the properties of biodegradation, non-toxicity, and biocompatibility mentioned above.…”

Developing Porous Microneedles Patch for the Detection of Wound Infections

“…[ 6 ] It is well‐documented that MNs are often divided into six categories based on the substrate material and structure: porous, solid, hollow, soluble, coated, and hydrogel MNs. [ 23,39,40 ] Porous MNs was particularly recognized for their efficacy in drug delivery. [ 41 ] Forming a transdermal drug delivery system, porous MNs, with numerous pores in their pedestal and tips, exhibit enhanced drug loading capabilities (Figure 2D).…”

“…Common degradable polymer materials include natural polymers, while non-degradable materials span ceramics, carbon, metals, and silicon. [39,49,50] The polymer materials involve polyethylene glycol diacrylate (PEGDA), gelatin methyl acryloyl, hyaluronic acid (HA), chitosan, and the like. [51] Hydrogel MNs extract ISF in a single step by utilizing their expansion capability, eliminating the need for additional auxiliary equipment.…”

“…To date, the most widely adopted manufacturing techniques include mold-based manufacturing, microfabrication (such as etching, lithography and laser), and 3D printing. [12,39] When utilizing molds to prepare MNs, the main structure was primarily obtained through methods such as laser ablation, microfabrication, 3D printing, and etching. The subsequent step involved filling the main structure with curing material, such as polydimethylsiloxane (PDMS), to create the negative mold, which was removed after complete curing.…”