An integrated flex-microfluidic-Si chip device towards sweat sensing applications
Introduction
The use of microfluidic point-of-care devices has been expanding in recent years, mainly driven by applications in medical diagnostics and wearable sensing [1], [2], [3], [4], [5], [6]. Especially for wearable sensing, it is beneficial to make the device mechanically flexible, since this enables integration into textile or clothes and, alternatively, it allows for easily attaching the device directly to the skin. Flexibility can be achieved by using compliant materials for device fabrication such as PDMS [7], [8], polymer foils [9], [10], [11] or paper [2], [12]. For medical diagnostics and wearable sensing, body liquids like blood, urine, sweat and saliva can be analyzed, depending on the application. In wearable sensing, sweat is a straightforward target since it is a body liquid that is accessible without serious interventions with the person, and it is produced continuously. Also, sweat contains relevant markers; for example, the pH of sweat is related to the sweat rate [13] and to the sodium concentration in sweat [14] both of which are important markers for a disease like cystic fibrosis. The pH of sweat influences the pH of the skin, which is an important pathogenesis of dermatoses such as atopic dermatitis [15]. In addition, the ion level in sweat indicates the status of body dehydration [16], [17], and alcohol and glucose levels in sweat might reflect their levels in blood [18], [19], [20]. To measure the presence of these markers, qualitatively or quantitatively, functional sensors or sensing materials are needed, and must be integrated into the sensing device.
Silicon based chips offer reliable and precise sensing and can be produced in continuously smaller sizes due to the advancements in cleanroom technology. Specifically for electrochemical sensing, high accuracy and sensitivity have been obtained by using silicon based chips [21]. It is possible to combine polymer foil based flexible electronics, including Si chip bonding, with microfluidic technology, to create flexible devices that can be worn directly on the human skin and/or integrated in bandages. In this way, wearable devices for continuous and prolonged sweat monitoring can be realized that combine the sensing accuracy of the Si chip with the mechanical flexibility of the foil-based microfluidics. An additional advantage of using foil technology is the potential of low cost manufacturing methods such as roll to roll technology for high volume production [22].
A challenge in developing such a wearable sweat monitoring device is to realize a continuous flow of sweat along the sensor. Bandodkar et al [23]. introduced a robust tattoo-like wearable sweat sensor for sodium concentration measurement, containing a fluidic channel for passively collecting the sweat, and including a piece of cellulose paper acting as perspiration sink. In our previous publication [24] we have shown that it is possible to achieve a controlled and continuous flow within a flexible microfluidic device in which: (1) liquid is collected from the surface to which the device is attached (i.e. the skin) by an absorbing structure in contact with the surface; (2) liquid is transported through a microchannel by capillarity; and (3) evaporation through a porous structure at the device outlet drives a continuous and prolonged flow through the channel, i.e. evaporative pumping occurs. In addition, we have shown that the flow rate generated in such a device can be monitored by visual observation of the liquid while it fills specially designed porous evaporation zones [9].
The aim of the work presented here is to design, fabricate, and test an integrated flexible microfluidic sensing device that can eventually be developed towards a wearable device for the real time monitoring of the composition of sweat. To achieve this, we integrate a Si-based electrochemical sensor chip in a flexible microfluidic device based on evaporative pumping. We show a proof of principle of the resulting prototype device, i.e. we achieve continuous liquid transportation, and we show that the sensor responds to sequentially applied pH changes in the liquid.
Section snippets
The design
The design of the wearable sweat sensing device is presented in Fig. 1a. It comprises a sweat intake principle based on paper, a microfluidic device in foil, evaporation zones that act both as an evaporative pump and as a digital flow meter [24], and a silicon sensing chip with electrical connections. When the device is attached to the skin, the paper absorbs sweat from the skin surface. The microfluidic structures in the foil, comprising structures such as microchannels and cavities, are
Fabrication steps
As shown schematically in Fig. 4, the sensing chip is fabricated by sputtering and patterning 10 nm Ti and 100 nm Pt as 200 μm × 200 μm bond pads at the edge of the chip, 50 μm wide contacting wires, and three circular electrodes with a radius of 150 μm and a pitch of 1 mm located in the center of the chip (see Fig. 4a). To protect the wires from the liquid, 200 nm SiO2, 600 nm Si3N4 and 200 nm SiO2 layers are sputtered on top forming a dielectric layer, as shown in Fig. 4b. Centered above the Pt
Experimental platform
After lamination of the polymer layers and bonding of the sensing chip as described in the previous sections, the device is ready for testing; Fig. 6 shows the integrated device. It is connected to a millivolt meter (JENCO 6230N) via a standard ZiF connector for monitoring the output over time. The output voltage is recorded every second during the experiments by a computer connected to the meter and running LabVIEW (National Instruments). Two pH buffer solutions (B5020 and B4770,
Reference measurements of the electrochemical sensing chip
To assess the sensitivity and offset of the electrochemical pH sensors in our experiments, 17 sensors were wirebonded on a PCB and we carried our reference measurements by placing them directly into bulk pH buffer solutions, identical to those used in our experiments. The reference data is shown in Fig. 7. Stable voltages were recorded ranging from −70 mV to 200 mV, when the sensors were placed in pH 7 buffer. A linear fit of the data revealed a reproducible sensitivity of 61 ± 1 mV per 1 pH change
Conclusions
In this work, we successfully designed, realized, and tested an integrated microfluidic device built from laser-structured flexible polymer substrates, and with an integrated silicon sensor chip. When the inlet of the device is placed on top of a liquid drop, the device takes up the liquid by capillary action, and by an evaporative pumping principle the liquid is continuously flown through a microchannel and along the integrated sensor, without the need for any external pumping. Hence, the
Acknowledgements
This work is supported by NanoNextNL (sub-project 10A), a micro and nanotechnology program of the Dutch government and 130 partners. This project is carried out in direct collaboration with Holst Centre, Eindhoven, the Netherlands. The authors would like to thank Roel Kusters and Ashok Sridhar from Holst Centre for their kind assistance with the surface mount technology processes: screen printing and flip chip bonding, and Rajesh Mandamparambil for his valuable advice.
Chuan Nie finished his M.Sc. in 2011 in Microtechnology at Chalmers University of Technology (CTH), Sweden. He is currently a Ph.D. student in Microsystems at Eindhoven University of Technology (the Netherlands). His major research interest is polymer based microfluidics devices for sweat sensing applications.
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Chuan Nie finished his M.Sc. in 2011 in Microtechnology at Chalmers University of Technology (CTH), Sweden. He is currently a Ph.D. student in Microsystems at Eindhoven University of Technology (the Netherlands). His major research interest is polymer based microfluidics devices for sweat sensing applications.
Dr. Arjan Frijns is assistant professor at the department of Mechanical Engineering of the Eindhoven University of Technology (the Netherlands). His main research interests include fundamental research on mass and heat transfer at the micro-scales, multi-scale modeling (MD, DSMC, hybrid MD-DSMC and CFD), AC-electro-osmosis and ferrofluidics as well as experimental validation (micro-PIV, 3D micro-PTV), with applications to (evaporative) micro-channel cooling and microfluidic and optofluidic sensors.
Dr. Marcel Zevenbergen is a senior researcher in the gas and ion sensors program at Holst Centre/imec (the Netherlands). He obtained his MSc degree in Physics from Delft University of Technology in 2005. In 2009, he obtained a PhD in Physics from the same university, working on nanofluidic electrochemical sensors for single molecule detection. He then moved to Holst Centre/imec focusing on developing novel sensor solutions for food, environmental and well-being applications.
Prof. Dr. Jaap den Toonder is a full professor and the chair of the Microsystems group at the Eindhoven University of Technology (the Netherlands). His current main research interests are Micro-fluidics, Out-of-cleanroom micro-fabrication technologies, Mechanical properties of biological cells and tissues, Nature-inspired micro-actuators and Organs on chips.