Overcoming technological barriers in microfluidics: Leakage testing

Abstract

The miniaturization of laboratory procedures for Lab-on-Chip (LoC) devices and translation to various platforms such as single cell analysis or Organ-on-Chip (OoC) systems are revolutionizing the life sciences and biomedical fields. As a result, microfluidics is becoming a viable technology for improving the quality and sensitivity of critical processes. Yet, standard test methods have not yet been established to validate basic manufacturing steps, performance, and safety of microfluidic devices. The successful development and widespread use of microfluidic technologies are greatly dependent on the community’s success in establishing widely supported test protocols. A key area that requires consensus guidelines is leakage testing. There are unique challenges in preventing and detecting leaks in microfluidic systems because of their small dimensions, high surface-area to volume ratios, low flow rates, limited volumes, and relatively high-pressure differentials over short distances. Also, microfluidic devices often employ heterogenous components, including unique connectors and fluid-contacting materials, which potentially make them more susceptible to mechanical integrity failures. The differences between microfluidic systems and traditional macroscale technologies can exacerbate the impact of a leak on the performance and safety on the microscale. To support the microfluidics community efforts in product development and commercialization, it is critical to identify common aspects of leakage in microfluidic devices and standardize the corresponding safety and performance metrics. There is a need for quantitative metrics to provide quality assurance during or after the manufacturing process. It is also necessary to implement application-specific test methods to effectively characterize leakage in microfluidic systems. In this review, different methods for assessing microfluidics leaks, the benefits of using different test media and materials, and the utility of leakage testing throughout the product life cycle are discussed. Current leakage testing protocols and standard test methods that can be leveraged for characterizing leaks in microfluidic devices and potential classification strategies are also discussed. We hope that this review article will stimulate more discussions around the development of gas and liquid leakage test standards in academia and industry to facilitate device commercialization in the emerging field of microfluidics.

Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility

“…Particular care should be given to the leak tightness and the absence of bubbles since these are the main failure causes of microfluidic systems ( Leung et al., 2022 ; Wang et al., 2012 ). A good summary of possible test methods for leak testing is available ( Silverio et al., 2022 ). At a higher level of production, for commercialized devices, it is recommended that the manufacturer follows GMP to ensure a reproducible product.…”

Next generation microfluidics: fulfilling the promise of lab-on-a-chip technologies

“…17,19 A common MF design software could be developed with standard material types, designs, connectors, and fabrication considerations. Standardized fabrication protocols, including material selection, fabrication methods, leakage tests, 24 and quality control processes could be developed. In addition, an open-source, public MF design repository can be created to store and share MF device designs and fabrication methods.…”

“…MF device submissions to the United States Food and Drug Administration (FDA) have substantially increased in recent years 19 and are projected to increase even more in the coming years. The reliability, failure modes, 24 and performance monitoring of MF devices are areas of concern for the FDA. Common testing methods, interconnections, and inter-compatibility standards are needed, such as modularity, assembly, and flow control in MF devices.…”

3D-printed droplet-based microfluidic sensor based on ion beam-induced graphitic electrodes on diamond for dopamine detection

“…This assembly was selected as it permits to easy the microfluidic device from the PCB chip to clean it before each experiment, permitting multiple uses for this device. It permits to perform all the experiments with a low possibility of leakage which represents one of the major problems in the field of microfluidics [15]. Also, in this configuration the electrical connection between the diamond biosensor, PCB chip, and detection electronic chain is made far from any contact with the solutions in the microfluidic device, reducing the risk of short circuit.…”