Enhancement of volume-specific power resolution and bonding of parylene microfluidic chip calorimeter

Abstract

Living cells undergo anabolic and catabolic metabolic pathways. Cellular metabolic rate pertains to the speed at which a cell performs metabolic processes, including energy production, chemical synthesis, and nutrient degradation. It quantifies the collective level of activity and effectiveness of the cell's metabolism. Cellular metabolic rate is a reliable measure of the physiological condition of cells and any alterations they may undergo. Chip calorimeter is an effective label-free tool for measuring cellular metabolic heat production in real time. The chip calorimeter is designed to measure hundreds of cells, and can even measure a single cell, whereas the normal bench-top calorimeter typically measures tens of thousands of cells. Nevertheless, numerous chip calorimeters suffer from inadequate resolution and challenges in sample manipulations, impeding accurate assessments of cell metabolism. The previous study demonstrated the high power resolution of a thin-film parylene microfluidic chip calorimeter with a vacuum-insulated design. Additionally, the integration of on-chip PDMS valves allowed accurate control over fluidic processes. The chip calorimeter utilized vanadium pentoxide thermistors with a high-temperature coefficient of resistance of $-4.3 %/K$. It achieved excellent power resolution in the range of many hundreds of $pW$, using only tens of $nL$ of sample. Double-layer PDMS microfluidics enabled precise fluid manipulation. The parylene microfluidics fabrication process involved the application of nano-adhesive layers created by iCVD for molding and bonding, resulting in the rapid creation of an expanded parylene chamber. Despite the significant benefits, there was still potential for enhancing the chamber volume to improve the chip's performance and addressing the bonding failure issue that arose during the manufacturing process, resulting in reduced yield in wafer-scale production. Unlike biological reactions, which may be regulated by altering concentration to manage heat generation, the metabolic power per cell exhibits a limited range of variability. Therefore, the volume-specific power resolution, defined as the power resolution of a chip calorimeter divided by its measurement chamber volume, is a crucial parameter for assessing the performance of the chip calorimeter in measuring the metabolic heat of cells. Furthermore, increasing the chamber space allows for a greater number of cells to be consistently sustained during the measurements. This study focuses on maximizing the volume-specific power resolution of parylene microfluidic chip calorimeter and minimizing the bonding failure. To improve the resolution of power measurement, we increased the volume of the chamber by two times. This was achieved by using a double-layer SU-8 chamber mold and a wafer bonding machine to increase the height of the measurement chamber. To mitigate the bonding failure, a surface profilometer was used to investigate flatness error. Better bonding was observed after edge bead removal was performed for PDMS mold. The chip calorimeter, which has a greater resolution for power per unit volume, is anticipated to make significant contributions to the field of cell-based assay for drug discovery. Additionally, it is predicted to find applications in various sectors of the pharmaceutical industry and biomedical fields.