Enhanced Interstitial Fluid Extraction and Rapid Analysis via Vacuum Tube‐Integrated Microneedle Array Device

Abstract Advancing the development of point‐of‐care testing (POCT) sensors that utilize interstitial fluid (ISF) presents considerable obstacles in terms of rapid sampling and analysis. Herein, an innovative strategy is introduced that involves the use of a 3D‐printed, hollow microneedle array patch (MAP), in tandem with a vacuum tube (VT) connected through a hose, to improve ISF extraction efficiency and facilitate expedited analysis. The employment of negative pressure by the VT allows the MAP device to effectively gather ≈18 µL of ISF from the dermis of a live rabbit ear within a concise period of 5 min. This methodology enables the immediate and minimally invasive measurement of glucose levels within the body, employing personal healthcare meters for quantification. The fusion of the VT and MAP technologies provides for their effortless integration into a comprehensive and mobile system for ISF analysis, accomplished by preloading the hose with custom sensing papers designed to detect specific analytes. Moreover, the design and functionality of this integrated VT‐MAP system are intuitively user‐friendly, eliminating the requirement for specialized medical expertise. This feature enhances its potential to make a significant impact on the field of decentralized personal healthcare.


Figure S1 .
Figure S1.The detailed geometry of the microneedle-based ISF extraction device.(A) The cross-section view of the MAP device with chamber.(B) and (C) The parametric design of single needle tip.(D) The top view of the MAP design.(E) The parametric design of the outlet port.(F) The detailed geometry of the hose.(G) The overall image of the vacuum tube-integrated MAP device.

Figure S2 .
Figure S2.Schematic illustration of the MAP-based device fabrication (A) and postprocessing steps (B).

Figure S3 .
Figure S3.Views of a 10×10 MAP and the size of 10×10 MAP measured by a vernier caliper.(A) The length of the 10×10 MAP.(B) The width of the 10×10 MAP chamber.(C) The height of the 10×10 MAP (miconeedle tips involved).

Figure S4 .
Figure S4.Stress-strain diagram of the MAP.The arrow indicates the yield strength of the MAP.

Figure S5 .
Figure S5.The skin recovery after the application of MAP penetration of the mice dorsal skin at the time points of 0 min (A), 5 min (B), 15 min (C), and 30 min (D), respectively.

Figure S7 .
Figure S7.The photo of the agarose gel after the removal of the MAP under a 5-min application of a 10 kPa negative pressure.

Figure S8 .
Figure S8.H&E-staining of the mouse skin pierced by the MAP with different vacuum degrees.(A) H&E-staining of the mouse skin which was applied with the VTcoupled MAP device.(B) H&E-staining of the mouse skin which was applied with the MAP under a 10 kPa vacuum.Scale bar: 50 μm.

Figure S9 .
Figure S9.In vivo detection of the glucose in the ISF extracted using the VT-coupled MAP device from the rabbit ear skin with a glucometer.

Figure S10 .
Figure S10.SEM images of microneedles before (A) and after compression test (B).

Figure S11 .
Figure S11.The mechanical compressive cycle test of the MAP for 10 times.

Figure S12 .
Figure S12.The VT-coupled and LFTS-functionalized MAP device for rapid extraction and lateral flow analysis of ISF.(A) The commercial GC lateral flow test kit (top) and the LFTS taken out from the kit (bottom).(B) A piece of LFTS with the size of 1.5×20 mm (bottom) tailored from a piece of factory-fresh LFTS (top).(C) The photo of the VT-coupled and LFTS-functionalized MAP device.(D) The photo of the VT-coupled MAP device for in vivo detection of GC in the rabbit ear skin.

Figure S13 .
Figure S13.Design and 3D modeling of the lab-made dark box on the Cinema4D modeling software.(A) Side view.(B) Diagram of assembly units.(C) Vertical view.(D) Internal vertical view.

Figure S14 .
Figure S14.Colorimetric analysis of the ISF glucose and pH based on the data from the sensing hose of the VT-coupled MAP device.(A) Plot of R, G, B values vs glucose concentrations.(B) Plot of R, G, B values vs pH values.

Figure S15 .
Figure S15.Designs and dimensions of the MAPs used for the experiments.(A) Images and 2D drawings of the 5 × 5 MAP.(B) Images and 2D drawings of the 8 × 8 MAP.(C) Images and 2D drawings of the 9 × 9 MAP.(D) Images and 2D drawings of the 10 × 10 MAP.

Table S2 .
Summary table of recent studies on ISF extraction techniques.