Microneedles for Optical Spectroscopy

Abstract

[Background] This project provides a proof of principle to use microneedles in combination with optical spectroscopy for bilirubin detection. For newborns, high bilirubin levels in the blood can lead to serious health consequences, such as jaundice, which can lead to brain damage. Therefore, it should be detected as early as possible. However, bilirubin monitoring of newborns in remote African areas is insufficient. In these areas the current invasive methods are time-consuming, and minimally invasive methods, such as bilirubinometers, are quite expensive, and may be inaccurate in babies with stronger skin pigmentation. In short, the conditions are not optimal to detect jaundice, and therefore an affordable method is needed to accurately and quickly measure the concentration of bilirubin. [Aim] The aim of this project was to develop microneedles for optical spectroscopy, and to test them in simulated skin to determine the usability for reflection measurements. [Fabrication] Microneedles are created by using microfabrication techniques with a focus on backside exposure. Multiple prototypes have been developed and evaluated based on dimensional properties. The prototype closest to the requirements was chosen to take measurements. These were the microneedles with an average length of 410 μm, an average base diameter of 106 μm and an average tip diameter of 43 μm. [Measurements] To test the microneedles for their performance, an indentation test, and transmission and reflection measurements has been performed. The indentation test showed that the average fracture point of one microneedle is at a force of 72.5 mN and an average displacement of 63 µm. The fracture point per area microneedle is on average 16.5 N/mm^2. Furthermore, transmission measurements have shown that the reduction in transmission is 70 % from the base and 75 % from the tip. Therefore, the maximum amount of light that can be used for reflection measurements is 7.5 %. Moreover, reflection measurements have shown that the differences in color concentrations in the simulated skin results in differences in absorption and therefore reflection values. Also, the measurements in simulated bilirubin (skin simulation with yellow colorant) showed a dip in the blue spectrum, e.g. at 460 nm, the absorption peak of bilirubin. [Conclusion] In this project microneedles have been developed that are minimally invasive, biocompatible, optically transparent, and easy-to-process. The first measurements have shown that it seems possible to use the microneedles in combination with optical spectroscopy to detect differences in “bilirubin” concentrations. Moreover, the microneedles can be used to puncture the skin without fracturing. However, the actual usability in the clinical setting still needs to be investigated. Other important recommendations for future research are research into measurements with real bilirubin; the optimal alignment between the microneedles and the optical spectrometer; optimization in the manufacturing process to cover the spaces between the microneedles; and possible other development methods for microneedles (e.g. 3D printing) and other designs (e.g. mirrors for efficient light use).