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Precision diagnostics using electrogating of liquids in capillary-driven microfluidics

Periodic Reporting for period 1 - e-Gates (Precision diagnostics using electrogating of liquids in capillary-driven microfluidics)

Reporting period: 2016-08-15 to 2018-08-14

"Microfluidic devices offer unique opportunities for diagnosing rapidly many types of diseases using pre-integrated reagents and small volumes of samples next to patients. One major limitation of microfluidics for POC diagnostics is the need to always adapt microfluidic chip architectures and assay protocols for each specific application. Given the huge number of POC tests that can be used to monitor human health, having a flexible, programmable microfluidic device would be ideal. However, this flexibility is largely hindered by the long-standing challenge to control and manipulate the autonomous flow of liquids along microfluidic channels in a simple and reliable manner without using active micro-components, which are typically complex to manufacture, bulky, power-hungry and expensive.

This project aimed to introduce a novel concept for controlling the flow of liquids filling microchannels in microfluidic chips. The concept is based on the stop-and-go actuation of gates, located at key locations along a flow path. When a liquid or sample is pipetted onto a loading pad (See. Fig. 1a), it spontaneously fills the flow path serviced by the loading pad due to capillary action and stops precisely at any gates that the liquid encounters. Stopping the flow is achieved by having a geometrical discontinuity along the flow path that pins the liquid due to a Laplace pressure barrier. However, the flow can be resumed by applying a voltage to the meniscus of liquid pinned at the gate, (Fig. 1b). The voltage increases the wetting properties of the geometrical discontinuity, which makes the liquid able to pass the gate. We termed such gates ""electrogates"" and bias them using a peripheral and specific protocols (selection of gate, voltage, voltage duration). The peripheral can be controlled using a smartphone application and standard wireless communication (e.g. Bluetooth), (Fig. 1c, d).

Electrogates can be integrated to microfluidic chips in silicon to select a flow path post-fabrication of the chips. This brings significant flexibility to such chips with flow paths and timing being programmed in a convenient manner using a simple user interface on a smartphone. One can envision deploying such a method to microfluidic chips used for diagnostics where duration of key biochemical steps can be optimized to match a desired sensitivity or where a liquid or sample can be passed inside specific microchannels for mixing, filtration, processing, etc. depending on what step would be optimal for a test. This offers remarkable opportunities considering that such a simple but efficient control over liquids can still be obtained using capillary forces and a simple peripheral for activating the desired electrogates. In addition, electrogates remain easy to fabricate and use low voltage and little power. They can also be multiplied on a microfluidic chip to allow multiplexed control of various liquids filling microfluidic chips in parallel.
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Our development of electrogates started with the analysis of relevant prior art for stop-and-go control of liquid flow in microsystems based on actuated valves, hydrophobic barriers and electrowetting. Some preliminary experiments were developed in the host institution to evaluate the performance of hydrophobic materials and Pd electrodes patterned on the bottom of silicon microchannels. The combination of findings from the literature and experimental observations allowed us to evaluate the pros and cons of the approaches.

Next, we went through the theoretical description and modeling of capillary-driven microfluidics and electrowetting phenomena, physics of microdevices and compatibility of microfabrication processes to define the optimal design features of the electrogating units in microfluidic chips. We consequently invented a novel but simple mechanism to control efficiently liquid filling in capillary-driven microchannels based on geometrical effects and electrowetting phenomena.

For the liquid pinning geometry, we have taken advantage of a suitable semicircular trench etched on an insulating hydrophilic surface at the bottom of the microchannel and a metal electrode patterned over the trench. The trench creates an efficient pinning of the liquid meniscus at the electrogate. The flow is resumed beyond the electrogate when a low DC voltage is applied between the electrode on the trench and an electrode in contact with the liquid sample in the loading pad. Using this simple but optimized electrogate geometry, we were able to stop and resume flow of numerous biological buffers (e.g. the phosphate buffered saline (PBS) solution) in a controlled manner.

Human serum can be more difficult to pin in microchannels because the adsorption of proteins from serum to surfaces can increase the wettability of microchannels. We found that the retention capability of human serum by electrogates can be strengthened using patterned Pd tiles before the trench. Electrogates were then successfully tested using biological samples such as human serum and artificial urine showing high reliability, short response time (< 1 sec), low voltage requirements (< 8 V) and exhibiting long-term stability (> 40 min). Moreover, they are easy to fabricate and compatible with multiple gates on one chip. The electrogates were implemented in Si microfluidic chips (1 x 2 cm2) comprising a loading pad to receive a liquid sample and metal electrodes to provide bias voltage for actuation of the electrogates.

The full functionality of electrogates was completed with the implementation of a small low-cost peripheral device having a battery, a control board and a BluetoothTM module for communication with a smartphone. This peripheral energizes the microfluidic chip (containing electrogates) according to a protocol sent by the smartphone so that assay protocols can be easily updated or modified almost “on the fly”. Communication is bidirectional and the chip/peripheral updates the smartphone application with the current state of filling of the microfluidic chip.
With a growing list of health conditions that can be monitored or diagnosed at the point-of-care, it is clear that portable diagnostics can play a very important role in supporting patients and healthcare workers. Effective and flexible solutions are needed for carrying out precise diagnostics tests outside of conventional, centralized clinical laboratories. Environmental monitoring and testing food products can also benefit from precise and portable analytical devices. This project provides a solid basis for devising high-performance diagnostic devices based on microfluidics and electrogates: electrogates enhance the functionalities of passive (capillary-based) microfluidics to create devices with generic architectures that can be triggered on-demand using a smartphone and a “liquid driving application”, thereby making these devices better connected, more precise and programmable. Therefore, electrogates represent an exciting and powerful function for microfluidics that should resonate with the large amount of work performed by the communities working on diagnostics, technologies for analytical devices, and healthcare. We already noticed such an interest during communication and dissemination of the work on electrogates to the academic and private sectors and to the public during, for example, plenary lectures in the most important conferences of the field (microTAS 2017 and Biosensors 2018).
(a-b) electrogates on a microfluidic chip, (c-d) peripheral and smartphone app for operation