A passive wearable microfluidic sensor for the 24 hour monitoring of intraocular pressure using a smartphone.

Continuous-flow microfluidic large-scale integration (mLSI) shows increasing importance in biological/chemical fields, thanks to its advantages in miniaturization and high throughput. Current mLSI is designed manually, which is time-consuming and error-prone. In recent years, design automation research for mLSI has evolved rapidly, aiming to replace manual labor by computers. However, previous design automation approaches used to design each microfluidic layer separately and over-simplify the layer interactions to various degrees, which resulted in a gap between realistic requirements and automatically generated designs. In this paper, we propose a module model library to accurately model microfluidic components involving layer interactions; and we propose a co-layout synthesis tool, Columba, which generates AutoCAD-compatible designs that fulfill all designs rules and can be directly used for mask fabrication. Columba takes plain-text netlist descriptions as inputs, and performs simultaneous placement and routing for multiple layers while ensuring the planarity of each layer. We validate Columba by fabricating two of its output designs. Columba is the first design automation tool that can seamlessly synchronize with the manufacturing flow.

Dilatometric strain sensors (DSS) that work based on detection of volume change in microfluidic channels; i) are highly sensitive to biaxial strain, ii) can be fabricated using only soft and transparent materials, and iii) are easy to integrate with smart-phones. These features are especially attractive for contact lens based intraocular pressure (IOP) sensing applications. The inherent flow stabilization of the microfluidic systems is an additional advantage suitable for filtering out rapid fluctuations. Here, we have demonstrated that the low-pass filtering in microfluidic sensors improves the signal-to-noise-ratio for ophthalmic applications. We have fabricated devices with a time constant in the range of 1–200 seconds. We have demonstrated that the device architecture and working liquid viscosity (10–866 cSt) are the two independent factors that determine the sensor time constant. We have developed an equivalent circuit model for the DSS that accurately represents the experimental results thus can be used as a computational model for design and development of microfluidic sensors. For a sensor with the time constant of 4 s, we report that microfluidic signal filtering in IOP monitoring applications can suppress the rapid fluctuations (i.e., the noise due to ocular pulsation, blinking etc.) by 9 dB without the need for electronic components.

This article is a tutorial on continuous-flow biochips where the basic building blocks are microchannels, and microvalves, and by combining them, more complex units such as mixers, switches, and multiplexers can be built. It also presents the state of the art in flow-based biochip technology and emerging research challenges in the areas of physical design and testing techniques.

Current digital biology platforms lack the ability to perform continuous measurements for transient analysis. A fundamental challenge is to perform complex fluidic manipulation processes such as washing and mixing in individual reaction volumes. Here, we present a reusable digital biology platform where the reaction compartmentalization and commencement are controlled by micromechanical valves fabricated in high density through microfluidic very large scale integration (mVLSI) technology. Background noise correction enabled by the platform improves signal-to-noise ratio and thus eliminates the need for sophisticated imaging technologies. We have used the detection platform for probing single molecules of the β-galactosidase enzyme. The measurements were repeated hundreds of times at concentrations as low as 0.8 fM (resulting in a theoretical detection limit of 3 aM). We have also demonstrated multiple TNF-α measurements with a magnetic bead based digital ELISA assay. The assay showed that the average number of enzymes per magnetic bead is 0.55 for 10 pM TNF-α (compared to 0.08 for negative control). This automated and reusable digital platform allows on-chip assay preparation and continuous measurements; as a result, it will enable single cell/enzyme studies and clinical diagnostic tests (i.e. digital ELISA) to be performed in shorter time scales and with lower detection limits.

The micromechanical valves that are used in microfluidic large-scale integration (mLSI) technology enable automated control of (bio)chemical and cell-based assays as they can perform crucial functions such as metering, mixing, pumping, and compartmentalization. The mLSI requires flow channels with a rounded profile for leak-free valve operation (i.e. ON/OFF flow control) to execute these functions. Here, we have used the deflection of an elastomeric membrane (DEM) in two configurations; free and constrained deflection, to fabricate reusable and tunable multi-height molds that in turn lead to fabrication of valvable flow channels in an unprecedented height range (up to 220 (130) µ m for free (constrained) deflection) for mLSI. The constrained deflection configuration enabled the fabrication of channels that are directly in contact with a substrate, which combines the advantages of push-down and push-up valves that are commonly used in mLSI. Compared to the use of rigid master molds, fabricated either by photolithography on silicon wafers or via other processes such as 3D printing, milling etc, the tunability advantage of the multi-height DEM molds, eliminates the requirement of a different mold for each channel height, thus increases the prototyping and device optimization efficiency. We have developed functional devices to demonstrate that our enhanced soft lithography technique is high-throughput, scalable, and reproducible. The flow of large particles (110 µ m diameter) were controlled that shows the suitability of the technique for organ- or spheroid-on-a-chip applications. The electrical resistance of liquid metal in microfluidic channels is modulated with a frequency of 1 kHz, showing the potential for re-configurable electronic circuits.