Device Processing Challenges for Miniaturized Sensing Systems Targeting Biological Fluids.

This article presents a review of device processing technologies used in the fabrication of biomedical systems, and highlights the requirements of advanced manufacturing technology. We focus on biomedical systems that perform diagnostics of fluidic specimens, with analytes that are in the liquid phase. In the introduction, we define biomedical systems as well as their versatile applications and the essential current trends. The paper gives an overview of the most important biomolecules that typically must be detected or analyzed in several applications. The paper is structured as follows. First, the conventional architecture and construction of a biosensing system is introduced. We provide an overview of the most common biosensing methods that are currently used for the detection of biomolecules and its analysis. We present an overview of reported biochips, and explain the technology of biofunctionalization and detection principles, including their corresponding advantages and disadvantages. Next, we introduce microfluidics as a method for delivery of the specimen to the biochip sensing area. A special focus lies on material requirements and on manufacturing technology for fabricating microfluidic systems, both for niche and mass-scale production segments. We formulate requirements and constraints for integrating the biochips and microfluidic systems. The possible impacts of the conventional microassembly techniques and processing methods on the entire biomedical system and its specific parts are also described. On that basis, we explain the need for alternative microassembly technologies to enable the integration of biochips and microfluidic systems into fully functional systems.