Label-free high-throughput detection and content sensing of individual droplets in microfluidic systems.

This study reports a microwave-microfluidics integrated approach capable of performing droplet detection at high-throughput as well as content sensing of individual droplets without chemical or physical intrusion. The sensing system consists of a custom microwave circuitry and a spiral-shaped microwave resonator that is integrated with microfluidic chips where droplets are generated. The microwave circuitry is very cost effective by using off-the-shelf components only. It eliminates the need for bulky benchtop equipment, and provides a compact, rapid and sensitive tool compatible for Lab-on-a-Chip (LOC) platforms. To evaluate the resonator's sensing capability, it was first applied to differentiate between single-phase fluids which are aqueous solutions with different concentrations of glucose and potassium chloride respectively by measuring its reflection coefficient as a function of frequency. The minimum concentration assessed was 0.001 g ml(-1) for potassium chloride and 0.01 g ml(-1) for glucose. In the droplet detection experiments, it is demonstrated that the microwave sensor is able to detect droplets generated at as high throughput as 3.33 kHz. Around two million droplets were counted over a period of ten minutes without any missing. For droplet sensing experiments, pairs of droplets that were encapsulated with biological materials were generated alternatively in a double T-junction configuration and clearly identified by the microwave sensor. The sensed biological materials include fetal bovine serum, penicillin antibiotic mixture, milk (2% mf) and d-(+)-glucose. This system has significant advantages over optical detection methods in terms of its cost, size and compatibility with LOC settings and also presents significant improvements over other electrical-based detection techniques in terms of its sensitivity and throughput.

[1]  Vijay Srinivasan,et al.  Development of a digital microfluidic platform for point of care testing. , 2008, Lab on a chip.

[2]  Min Gu,et al.  Microfluidic sensing: state of the art fabrication and detection techniques. , 2011, Journal of biomedical optics.

[3]  N. Perrimon,et al.  Droplet microfluidic technology for single-cell high-throughput screening , 2009, Proceedings of the National Academy of Sciences.

[4]  Fadhel M. Ghannouchi,et al.  The Six-Port Technique With Microwave and Wireless Applications , 2009 .

[5]  M. Tabrizian,et al.  Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics. , 2012, Lab on a chip.

[6]  G. Engen The Six-Port Reflectometer: An Alternative Network Analyzer , 1977 .

[7]  Andrew D Griffiths,et al.  Multi-step microfluidic droplet processing: kinetic analysis of an in vitro translated enzyme. , 2009, Lab on a chip.

[8]  Gang Li,et al.  A droplet-based pH regulator in microfluidics. , 2014, Lab on a chip.

[9]  Nam-Trung Nguyen,et al.  Rare cell isolation and analysis in microfluidics. , 2014, Lab on a chip.

[10]  Charles N Baroud,et al.  Dynamics of microfluidic droplets. , 2010, Lab on a chip.

[11]  Tomasz Glawdel,et al.  Passive droplet trafficking at microfluidic junctions under geometric and flow asymmetries. , 2011, Lab on a chip.

[12]  W. Hirst,et al.  Chapter 3 Small-Molecule Protein–Protein Interaction Inhibitors as Therapeutic Agents for Neurodegenerative Diseases: Recent Progress and Future Directions , 2009 .

[13]  D. Weitz,et al.  Droplet microfluidics for high-throughput biological assays. , 2012, Lab on a chip.

[14]  K. Mitton,et al.  High-performance liquid chromatography-electrochemical detection of antioxidants in vertebrate lens: glutathione, tocopherol, and ascorbate. , 1994, Methods in enzymology.

[15]  John Ardizzoni A Practical Guide to High-Speed Printed-Circuit-Board Layout , 2005 .

[16]  M. S. Boybay,et al.  Microwave sensing and heating of individual droplets in microfluidic devices. , 2013, Lab on a chip.

[17]  Hongwei Zhu,et al.  Au nanoparticles enhanced fluorescence detection of DNA hybridization in picoliter microfluidic droplets , 2014, Biomedical microdevices.

[18]  Jiseok Lim,et al.  Micro-optical lens array for fluorescence detection in droplet-based microfluidics† †Electronic supplementary information (ESI) available: Supplementary Figures (S1 and S2). Supplementary movie 01: movie recorded by a high-speed camera without backlight illumination. Supplementary movie 02: movie re , 2013, Lab on a chip.

[19]  Jongin Hong,et al.  Thermoset polyester droplet-based microfluidic devices for high frequency generation. , 2011, Lab on a chip.

[20]  J. Delville,et al.  Real-time droplet caliper for digital microfluidics , 2012 .

[21]  Carolyn L. Ren,et al.  Global network design for robust operation of microfluidic droplet generators with pressure-driven flow , 2012 .

[22]  Tao Dong,et al.  Recent Developments in Optical Detection Technologies in Lab-on-a-Chip Devices for Biosensing Applications , 2014, Sensors.

[23]  Rustem F Ismagilov,et al.  Formation of droplets of alternating composition in microfluidic channels and applications to indexing of concentrations in droplet-based assays. , 2004, Analytical chemistry.

[24]  T. Mohamed,et al.  Tau-derived-hexapeptide 306VQIVYK311 aggregation inhibitors: nitrocatechol moiety as a pharmacophore in drug design. , 2013, ACS chemical neuroscience.

[25]  Tomasz Glawdel,et al.  Droplet formation in microfluidic T-junction generators operating in the transitional regime. I. Experimental observations. , 2012, Physical review. E, Statistical, nonlinear, and soft matter physics.

[26]  Andrew D Griffiths,et al.  A fast and efficient microfluidic system for highly selective one-to-one droplet fusion. , 2009, Lab on a chip.

[27]  Daniel T Chiu,et al.  Ultrasensitive and high-throughput fluorescence analysis of droplet contents with orthogonal line confocal excitation. , 2010, Analytical chemistry.

[28]  Caglar Elbuken,et al.  Detection of microdroplet size and speed using capacitive sensors , 2011 .

[30]  T. Huang,et al.  Cell separation using tilted-angle standing surface acoustic waves , 2014, Proceedings of the National Academy of Sciences.

[31]  Thomas S. Peat,et al.  Enzyme synthesis and activity assay in microfluidic droplets on a chip , 2011 .

[32]  J. Eijkel,et al.  Time-resolved electrochemical measurement device for microscopic liquid interfaces during droplet formation , 2013 .

[33]  Qian Wang,et al.  Highly sensitive and homogeneous detection of membrane protein on a single living cell by aptamer and nicking enzyme assisted signal amplification based on microfluidic droplets. , 2014, Analytical chemistry.

[34]  A. van den Berg,et al.  Label-free, high-throughput, electrical detection of cells in droplets. , 2012, The Analyst.

[35]  C. Harnett,et al.  hin-film electrode based droplet detection for microfluidic systems , 2011 .

[36]  Werasak Surareungchai,et al.  Multi-channel PMMA microfluidic biosensor with integrated IDUAs for electrochemical detection , 2013, Analytical and Bioanalytical Chemistry.

[37]  V. Adam,et al.  Electrochemistry as a Tool for Studying Antioxidant Properties , 2013, International Journal of Electrochemical Science.