Using LIGA in fabrication of Microfluidic Device for Diagnostic Analysis of Human Body Fluid

Currently a lot of research is being conducted in the area of non‐invasive diagnostics [1]. Therefore, body fluids like saliva and sweat, the easily accessible non‐controversial mediums have recently been the focal point of research on markers for health and disease monitoring in human beings [2]. The research conducted in this study focuses on LIGA (German acronym lithography, electroplating and molding)/ micro‐electro‐mechanical systems (MEMS) based solution for multiple ion measurement (marker for health/disease monitoring) from bodily fluids by providing a user friendly diagnostic chip and an instrument/reader for the convenient display of results. This work continues our research presented recently where we designed and fabricated a microfluidic polymeric chip (sweatstick) to collect 600 µl of human sweat that was analyzed to measure the Ca 2+ ion content to diagnose bone mass loss [3]. However, this required processing by skilled personnel using conventional centrifuge separation and other analytical equipment in a laboratory setting. In order to overcome this limitation we developed a user‐friendly BioMEMS analytical device capable of performing point‐of‐care, multiple diagnostic analysis of human body fluid collected using the sweatstick. This device uses the electronics and a microcontroller to run the analysis automatically and independent of skilled personnel. The present devices’ function is to perform a diagnostic analysis of Ca 2+ and Cl ‐ ions content using the colorimetric assays for bone mineral density loss and cystic fibrosis, respectively [4‐5]. The micro‐ controller and the electronics were built around a microfluidic chip with two analytical chambers measuring 2 x 2 x 60 mm that could test body fluid samples for any two analysis/ions simultaneously. The detection method being absorbance based, therefore a super‐bright LED provided the light and a photodiode read the absorbance. The LED/photodiode pair is placed at the ends of the chambers. After sample collection and extraction, a measured amount of reagent and sample were mixed and trans‐ ported to the analytical chambers by using off‐chip solenoid type micropumps. The results for Ca 2+ analysis obtained were linear and sensitive enough to make it a viable diagnostic device. However, in order to further reduce the error margins mainly caused by uncontrolled air bubble formation affecting the absorbance signal, a better pump concept (micropump/vacuum micropump combination) is designed. The dimensions of the analytical chamber causes the flow to be laminar thereby making it extremely difficult for on‐chip mixing. Therefore, off‐chip mixing was performed. The mixing channels (250 x 450 µm and 250 x 150 µm) are designed to facilitate on‐chip mixing and further miniaturization of the device. The new disposable chip design also includes fixed housing for the photodiode/LED setup to make the device more robust with respect to consistent sensing of the colorimetric assay. The entire process will be controlled by a microcontroller along with performing the calculations and providing the results to the user.