Karnati Chandana, Aguilar Ricardo, Arrowood Colin, Ross James, Rajaraman Swaminathan
Alcon Laboratories, Duluth, GA 30097, USA.
Intel Corporation, Hillsboro, OR 97124, USA.
Micromachines (Basel). 2017 Aug 15;8(8):250. doi: 10.3390/mi8080250.
We report on microfabrication and assembly process development on transparent, biocompatible polymers for patterning electrodes and growing electrically active cells for cell-based biosensor applications. Such biosensors are typically fabricated on silicon or glass wafers with traditional microelectronic processes that can be cost-prohibitive without imparting necessary biological traits on the devices, such as transparency and compatibility for the measurement of electrical activity of electrogenic cells and other biological functions. We have developed and optimized several methods that utilize traditional micromachining and non-traditional approaches such as printed circuit board (PCB) processing for fabrication of electrodes and growing cells on the transparent polymers polyethylene naphthalate (PEN) and polyethylene terephthalate (PET). PEN-based biosensors are fabricated utilizing lithography, metal lift-off, electroplating, wire bonding, inkjet printing, conformal polymer deposition and laser micromachining, while PET-based biosensors are fabricated utilizing post-processing technologies on modified PCBs. The PEN-based biosensors demonstrate 85⁻100% yield of microelectrodes, and 1-kHz impedance of 59.6 kOhms in a manner comparable to other traditional approaches, with excellent biofunctionality established with an ATP assay. Additional process characterization of the microelectrodes depicts expected metal integrity and trace widths and thicknesses. PET-based biosensors are optimized for a membrane bow of 6.9 to 15.75 µm and 92% electrode yield on a large area. Additional qualitative optical assay for biomaterial recognition with transmitted light microscopy and growth of rat cortical cells for 7 days (DIV) targeted at biological functionalities such as electrophysiology measurements are demonstrated in this paper.
我们报告了用于制造电极和培养电活性细胞以用于基于细胞的生物传感器应用的透明生物相容性聚合物的微加工和组装工艺开发。此类生物传感器通常采用传统微电子工艺在硅或玻璃晶圆上制造,这可能成本高昂,且无法赋予器件必要的生物学特性,如透明度以及对产电细胞电活动测量和其他生物学功能的兼容性。我们开发并优化了多种方法,这些方法利用传统微加工和非传统方法,如印刷电路板(PCB)加工,在透明聚合物聚萘二甲酸乙二醇酯(PEN)和聚对苯二甲酸乙二醇酯(PET)上制造电极并培养细胞。基于PEN的生物传感器利用光刻、金属剥离、电镀、引线键合、喷墨打印、保形聚合物沉积和激光微加工制造,而基于PET的生物传感器则利用在改性PCB上的后处理技术制造。基于PEN的生物传感器显示微电极的成品率为85%至100%,1 kHz时的阻抗为59.6 kΩ,与其他传统方法相当,通过ATP测定建立了优异的生物功能。微电极的额外工艺表征描绘了预期的金属完整性以及走线宽度和厚度。基于PET的生物传感器针对6.9至15.75 µm的膜弯曲和大面积92%的电极成品率进行了优化。本文展示了利用透射光显微镜对生物材料识别的额外定性光学分析以及针对电生理学测量等生物学功能培养大鼠皮质细胞7天(DIV)的情况。