Yuksel Temiz

‘Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (~1 μm). The hydrophilicity (advancing contact angle of ~60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min-1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers.

Arraying single microbeads in microchannels using dielectrophoresis-assisted mechanical traps

Manipulating and immobilizing single microbeads in flowing fluids is relevant for biological assays and chemical tests but typically requires expensive laboratory equipment and trapping mechanisms that are not reversible. In this paper, we present a highly efficient and reversible mechanism for trapping microbeads by combining dielectrophoresis (DEP) with mechanical traps. The integration of planar electrodes and mechanical traps in a microchannel enables versatile manipulation of microbeads via DEP for their docking in recessed structures of mechanical traps. By simulating the combined effects of the hydrodynamic drag and DEP forces on microbeads, we explore a configuration of periodic traps where the beads are guided by the electrodes and immobilized in recess areas of the traps. The design of the electrode layout and operating configuration are optimized for the efficient trapping of single microbeads. We demonstrated the predicted guiding and trapping effectiveness of the design as well as the reversi...

Capillary-driven microfluidic chips with evaporation-induced flow control and dielectrophoretic microbead trapping

Abstract. This work reports our efforts on developing simple-to-use microfluidic devices for point-of-care diagnostic applications with recent extensions that include the trapping of microbeads using dielectrophoresis (DEP) and the modulation of the liquid flow using integrated microheaters. DEP serves the purpose of trapping microbeads coated with receptors and analytes for detection of a fluorescent signal. The microheater is actuated once the chip is filled by capillarity, creating an evaporation-induced flow tuned according to assay conditions. The chips are composed of a glass substrate patterned with 50-nm-thick Pd electrodes and microfluidic structures made using a 20-μm-thick dry-film resist (DFR). Chips are covered/sealed by low temperature (50°C) lamination of a 50-μm-thick DFR layer having excellent optical and mechanical properties. To separate cleaned and sealed chips from the wafer, we used an effective chip singulation technique which we informally call the “chip-olate” process. In the experimental section, we first studied dielectrophoretic trapping of 10-μm beads for flow rates ranging from 80  pL s−1 to 2.5  nL s−1 that are generated by an external syringe pump. Then, we characterized the embedded microheater in DFR-covered chips. Flow rates as high as 8  nL s−1 were generated by evaporation-induced flow when the heater was biased by 10 V, corresponding to 270-mW power. Finally, DEP-based trapping and fluorescent detection of functionalized beads were demonstrated as the flow was generated by evaporation-induced flow after the microfluidic structures were filled by capillarity.

Internet of the body and cognitive hypervisor

Wearables that continuously acquire medically relevant parameters can reduce duration of hospitalizations and derive treatment optimizations for individual patients thus improving the quality of medical treatments. We demonstrate an architecture that includes wearables, edge and cloud computing to provide optimal user interaction and analytics of multi-parameter wearable data to accomplish this goal. We also explore the trade-offs of on-wearable processing versus raw data transmission and the use of commercial location monitors to acquire indoor location data.

Chemiluminescence generation and detection in a capillary-driven microfluidic chip

The use of microfluidic technology represents a strong opportunity for providing sensitive, low-cost and rapid diagnosis at the point-of-care and such a technology might therefore support better, faster and more efficient diagnosis and treatment of patients at home and in healthcare settings both in developed and developing countries. In this work, we consider luminescence-based assays as an alternative to well-established fluorescence-based systems because luminescence does not require a light source or expensive optical components and is therefore a promising detection method for point-of-care applications. Here, we show a proof-of-concept of chemiluminescence (CL) generation and detection in a capillary-driven microfluidic chip for potential immunoassay applications. We employed a commercial acridan-based reaction, which is catalyzed by horseradish peroxidase (HRP). We investigated CL generation under flow conditions using a simplified immunoassay model where HRP is used instead of the complete sandwich immunocomplex. First, CL signals were generated in a capillary microfluidic chip by immobilizing HRP on a polydimethylsiloxane (PDMS) sealing layer using stencil deposition and flowing CL substrate through the hydrophilic channels. CL signals were detected using a compact (only 5×5×2.5 cm3) and custom-designed scanner, which was assembled for less than

Single-bead arrays for fluorescence-based immunoassays on capillary-driven microfluidic chips

30 and comprised a 128×1 photodiode array, a mini stepper motor, an Arduino microcontroller, and a 3D-printed housing. In addition, microfluidic chips having specific 30-μm-deep structures were fabricated and used to immobilize ensembles of 4.50 μm beads functionalized with HRP so as to generate high CL signals from capillary-driven chips.

Sub-nanoliter, real-time flow monitoring in microfluidic chips using a portable device and smartphone

We report a concept for the simple fabrication of easy-to-use chips for immunoassays in the context of point-of-care diagnostics. The chip concept comprises mainly three features: (1) the efficient integration of reagents using beads functionalized with receptors, (2) the generation of capillary-driven liquid flows without using external pumps, and (3) a high-sensitivity detection of analytes using fluorescence microscopy. We fabricated prototype chips using dry etching of Si wafers. 4.5-μm-diameter beads were integrated into hexagonal arrays by sedimentation and removing the excess using a stream of water. We studied the effect of different parameters and showed that array occupancies from 30% to 50% can be achieved by pipetting a 250 nL droplet of 1% bead solution and allowing the beads sediment for 3 min. Chips with integrated beads were sealed using a 50-μm-thick dry-film resist laminated at 45 °C. Liquids pipetted to loading pads were autonomously pulled by capillary pumps at a rate of 0.35 nL s-1 for about 30 min. We studied ligand-receptor interactions and binding kinetics using time-lapse fluorescence microscopy and demonstrated a 5 pM limit of detection (LOD) for an anti-biotin immunoassay. As a clinically-relevant example, we implemented an immunoassay to detect prostate specific antigen (PSA) and showed an LOD of 108 fM (i.e. 3.6 pg mL-1). While a specific implementation is provided here for the detection of PSA, we believe that combining capillary-driven microfluidics with arrays of single beads and fluorescence readout to be very flexible and sufficiently sensitive for the detection of other clinically-relevant analytes.

Electrogates for stop-and-go control of liquid flow in microfluidics

The ever-increasing need for portable, easy-to-use, cost-effective, and connected point-of-care diagnostics (POCD) has been one of the main drivers of recent research on lab-on-a-chip (LoC) devices. A majority of these devices use microfluidics to manipulate precisely samples and reagents for bioanalysis. However, filling microfluidic devices with liquid can be prone to failure. For this reason, we have implemented a simple, yet efficient method for monitoring liquid displacement in microfluidic chips using capacitive sensing and a compact (75 mm × 30 mm × 10 mm), low-cost (

Capillary-Driven Microfluidic Chips for Miniaturized Immunoassays: Patterning Capture Antibodies Using Microcontact Printing and Dry-Film Resists.

60), and battery-powered (10-hour autonomy) device communicating with a smartphone. We demonstrated the concept using a capillary-driven microfluidic chip comprising two equivalent flow paths, each with a total volume of 420 nL. Capacitance measurements from a pair of electrodes patterned longitudinally along the flow paths yielded 17 pL resolution in monitoring liquid displacement at a sampling rate of 1 data/s (~1 nL/min resolution in the flow rate). We characterized the system using human serum, biological buffers, and water, and implemented an algorithm to provide real-time information on flow conditions occurring in a microfluidic chip and interactive guidance to the user.

Lab-on-a-chip devices

Diagnostics based on microfluidic devices necessitate specific reagents, flow conditions, and kinetics for optimal performance. Such an optimization is often achieved using assay-specific microfluidic chip designs or systems with external liquid pumps. Here, we present “electrogates” for stop-and-go control of flow of liquids in capillary-driven microfluidic chips by combining liquid pinning and electrowetting. Electrogates are simple to fabricate and efficient: a sample pipetted to a microfluidic chip flows autonomously in 15-μm-deep hydrophilic channels until the liquid meniscus is pinned at the edge of a 1.5-μm-deep trench patterned at the bottom of a rectangular microchannel. The flow can then be resumed by applying a DC voltage between the liquid and the trench via integrated electrodes. Using a trench geometry with a semicircular shape, we show that retention times longer than 30 min are achieved for various aqueous solutions such as biological buffers, artificial urine, and human serum. We studied ...