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11 pages, 9604 KiB

Open AccessArticle

On-Chip Cell Staining and Counting Platform for the Rapid Detection of Blood Cells in Cerebrospinal Fluid

by Yujin Lee, Byeongyeon Kim and Sungyoung Choi

Sensors 2018, 18(4), 1124; https://doi.org/10.3390/s18041124 - 7 Apr 2018

Cited by 15 | Viewed by 7661

Abstract

Counting blood cells in cerebrospinal fluid (CSF) is indispensable for diagnosing several pathological conditions in the central nervous system, such as meningitis, even though collecting CSF samples is invasive. Cell counting methods, such as hemocytometer chambers and flow cytometers, have been used for [...] Read more.

Counting blood cells in cerebrospinal fluid (CSF) is indispensable for diagnosing several pathological conditions in the central nervous system, such as meningitis, even though collecting CSF samples is invasive. Cell counting methods, such as hemocytometer chambers and flow cytometers, have been used for CSF cell counting, but they often lack the sensitivity to detect low blood cell numbers. They also depend on off-chip, manual sample preparation or require bulky, costly equipment, thereby limiting their clinical utility. Here, we present a portable cell counting platform for simple, rapid CSF cell counting that integrates a microfluidic cell counting chamber with a miniaturized microscope. The microfluidic chamber is designed not only to be a reagent container for on-chip cell staining but also to have a large control volume for accurate cell counting. The proposed microscope miniaturizes both bright-field and fluorescence microscopy with a simple optical setup and a custom cell-counting program, thereby allowing rapid and automated cell counting of nucleated white blood cells and non-nucleated red blood cells in fluorescence and bright-field images. Using these unique features, we successfully demonstrate the ability of our counting platform to measure low CSF cell counts without sample preparation. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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10 pages, 47090 KiB

Open AccessArticle

Oil Motion Control by an Extra Pinning Structure in Electro-Fluidic Display

by Yingying Dou, Biao Tang, Jan Groenewold, Fahong Li, Qiao Yue, Rui Zhou, Hui Li, Lingling Shui, Alex Henzen and Guofu Zhou

Sensors 2018, 18(4), 1114; https://doi.org/10.3390/s18041114 - 6 Apr 2018

Cited by 17 | Viewed by 4736

Abstract

Oil motion control is the key for the optical performance of electro-fluidic displays (EFD). In this paper, we introduced an extra pinning structure (EPS) into the EFD pixel to control the oil motion inside for the first time. The pinning structure canbe fabricated [...] Read more.

Oil motion control is the key for the optical performance of electro-fluidic displays (EFD). In this paper, we introduced an extra pinning structure (EPS) into the EFD pixel to control the oil motion inside for the first time. The pinning structure canbe fabricated together with the pixel wall by a one-step lithography process. The effect of the relative location of the EPS in pixels on the oil motion was studied by a series of optoelectronic measurements. EPS showed good control of oil rupture position. The properly located EPS effectively guided the oil contraction direction, significantly accelerated switching on process, and suppressed oil overflow, without declining in aperture ratio. An asymmetrically designed EPS off the diagonal is recommended. This study provides a novel and facile way for oil motion control within an EFD pixel in both direction and timescale. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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12 pages, 3181 KiB

Open AccessArticle

A Compact Microwave Microfluidic Sensor Using a Re-Entrant Cavity

by Hayder Hamzah, Ali Abduljabar, Jonathan Lees and Adrian Porch

Sensors 2018, 18(3), 910; https://doi.org/10.3390/s18030910 - 19 Mar 2018

Cited by 34 | Viewed by 5814

Abstract

A miniaturized 2.4 GHz re-entrant cavity has been designed, manufactured and tested as a sensor for microfluidic compositional analysis. It has been fully evaluated experimentally with water and common solvents, namely methanol, ethanol, and chloroform, with excellent agreement with the expected behaviour predicted [...] Read more.

A miniaturized 2.4 GHz re-entrant cavity has been designed, manufactured and tested as a sensor for microfluidic compositional analysis. It has been fully evaluated experimentally with water and common solvents, namely methanol, ethanol, and chloroform, with excellent agreement with the expected behaviour predicted by the Debye model. The sensor’s performance has also been assessed for analysis of segmented flow using water and oil. The samples’ interaction with the electric field in the gap region has been maximized by aligning the sample tube parallel to the electric field in this region, and the small width of the gap (typically 1 mm) result in a highly localised complex permittivity measurement. The re-entrant cavity has simple mechanical geometry, small size, high quality factor, and due to the high concentration of electric field in the gap region, a very small mode volume. These factors combine to result in a highly sensitive, compact sensor for both pure liquids and liquid mixtures in capillary or microfluidic environments. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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18 pages, 7080 KiB

Open AccessArticle

Simultaneous Detection of Two Chemicals Using a TE₂₀-Mode Substrate-Integrated Waveguide Resonator

by Ahmed Salim, Muhammad Usman Memon and Sungjoon Lim

Sensors 2018, 18(3), 811; https://doi.org/10.3390/s18030811 - 7 Mar 2018

Cited by 31 | Viewed by 6426

Abstract

Microwave resonators working as sensors can detect only a single analyte at a time. To address this issue, a TE₂₀-mode substrate-integrated waveguide (SIW) resonator is exploited, owing to its two distinct regions of high-intensity electric fields, which can be manipulated by [...] Read more.

Microwave resonators working as sensors can detect only a single analyte at a time. To address this issue, a TE₂₀-mode substrate-integrated waveguide (SIW) resonator is exploited, owing to its two distinct regions of high-intensity electric fields, which can be manipulated by loading two chemicals. Two microfluidic channels with unequal fluid-carrying capacities, engraved in a polydimethylsiloxane (PDMS) sheet, can perturb the symmetric electric fields even if loaded with the two extreme cases of dielectric [ethanol (E), deionized water (DI)] and [deionized water, ethanol]. The four layers of the sandwiched structure considered in this study consisted of a top conductive pattern and a bottom ground, both realized on a Rogers RT/Duroid 5880. PDMS-based channels attached with an adhesive serve as the middle layers. The TE₂₀-mode SIW with empty channels resonates at 8.26 GHz and exhibits a −25 dB return loss with an unloaded quality factor of Q ≈ 28. We simultaneously load E and DI and demonstrate the detection of the four possible combinations: [E, DI], [DI, E], [E, E], and [DI, DI]. The performance of our proposed method showed increases in sensitivity (MHz/ε_r) of 7.5%, 216%, and 1170% compared with three previously existing multichannel microwave chemical sensors. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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17 pages, 2429 KiB

Open AccessArticle

Calcium Imaging of GPCR Activation Using Arrays of Reverse Transfected HEK293 Cells in a Microfluidic System

by Margriet Roelse, Maurice G.L. Henquet, Harrie A. Verhoeven, Norbert C.A. De Ruijter, Ron Wehrens, Marco S. Van Lenthe, Renger F. Witkamp, Robert D. Hall and Maarten A. Jongsma

Sensors 2018, 18(2), 602; https://doi.org/10.3390/s18020602 - 16 Feb 2018

Cited by 3 | Viewed by 7748

Abstract

Reverse-transfected cell arrays in microfluidic systems have great potential to perform large-scale parallel screening of G protein-coupled receptor (GPCR) activation. Here, we report the preparation of a novel platform using reverse transfection of HEK293 cells, imaging by stereo-fluorescence microscopy in a flowcell format, [...] Read more.

Reverse-transfected cell arrays in microfluidic systems have great potential to perform large-scale parallel screening of G protein-coupled receptor (GPCR) activation. Here, we report the preparation of a novel platform using reverse transfection of HEK293 cells, imaging by stereo-fluorescence microscopy in a flowcell format, real-time monitoring of cytosolic calcium ion fluctuations using the fluorescent protein Cameleon and analysis of GPCR responses to sequential sample exposures. To determine the relationship between DNA concentration and gene expression, we analyzed cell arrays made with variable concentrations of plasmid DNA encoding fluorescent proteins and the Neurokinin 1 (NK1) receptor. We observed pronounced effects on gene expression of both the specific and total DNA concentration. Reverse transfected spots with NK1 plasmid DNA at 1% of total DNA still resulted in detectable NK1 activation when exposed to its ligand. By varying the GPCR DNA concentration in reverse transfection, the sensitivity and robustness of the receptor response for sequential sample exposures was optimized. An injection series is shown for an array containing the NK1 receptor, bitter receptor TAS2R8 and controls. Both receptors were exposed 14 times to alternating samples of two ligands. Specific responses remained reproducible. This platform introduces new opportunities for high throughput screening of GPCR libraries. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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13 pages, 6244 KiB

Open AccessArticle

Microfluidic High-Q Circular Substrate-Integrated Waveguide (SIW) Cavity for Radio Frequency (RF) Chemical Liquid Sensing

by Muhammad Usman Memon and Sungjoon Lim

Sensors 2018, 18(1), 143; https://doi.org/10.3390/s18010143 - 6 Jan 2018

Cited by 42 | Viewed by 6887

Abstract

In this study, a high-Q circular substrate-integrated waveguide (SIW) cavity resonator is proposed as a non-contact and non-invasive radio frequency (RF) sensor for chemical sensing applications. The design of the structure utilizes SIW technology along with a circular shape to achieve a high [...] Read more.

In this study, a high-Q circular substrate-integrated waveguide (SIW) cavity resonator is proposed as a non-contact and non-invasive radio frequency (RF) sensor for chemical sensing applications. The design of the structure utilizes SIW technology along with a circular shape to achieve a high unloaded Q factor, which is one of the important requirements for RF sensors. The resonant frequency of the proposed circular SIW cavity sensor changes when a liquid material or a chemical (microliters) is inserted in the sensitive area of the structure. The sensing of liquid materials with different permittivities is accomplished via the perturbation of the electric fields in the SIW configuration. When a microwell that is 4 mm in radius is installed vertically through the center of the bare circular SIW cavity, the operating frequency varies from 5.26 to 5.34 GHz. Similarly, when the microwell contains ethanol, the frequency shifts from 5.26 to 5.18 GHz, and the amplitude of reflection coefficient is shifted from −29 dB to −17 dB; when the microwell contains mixing deionized (DI)-water, the frequency moves from 5.26 to 4.98 GHz (which is also 0% Ethanol in our study), and the amplitude of reflection coefficient is shifted from −29 dB to −8 dB. A high unloaded Q factor is maintained throughout all experimental results. To demonstrate our idea, different concentrations of ethanol are tested and recorded. The experimental validation yields a close agreement between the simulations and the measurements. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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10491 KiB

Open AccessArticle

A Microwave Microfluidic Sensor Based on a Dual-Mode Resonator for Dual-Sensing Applications

by Nikolina Jankovic and Vasa Radonic

Sensors 2017, 17(12), 2713; https://doi.org/10.3390/s17122713 - 24 Nov 2017

Cited by 50 | Viewed by 6505

Abstract

In this paper, we propose a novel microwave microfluidic sensor with dual-sensing capability. The sensor is based on a dual-mode resonator that consists of a folded microstrip line loaded with interdigital lines and a stub at the plane of symmetry. Due to the [...] Read more.

In this paper, we propose a novel microwave microfluidic sensor with dual-sensing capability. The sensor is based on a dual-mode resonator that consists of a folded microstrip line loaded with interdigital lines and a stub at the plane of symmetry. Due to the specific configuration, the resonator exhibits two entirely independent resonant modes, which allows simultaneous sensing of two fluids using a resonance shift method. The sensor is designed in a multilayer configuration with the proposed resonator and two separated microfluidic channels—one intertwined with the interdigital lines and the other positioned below the stub. The circuit has been fabricated using low-temperature co-fired ceramics technology and its performance was verified through the measurement of its responses for different fluids in the microfluidic channels. The results confirm the dual-sensing capability with zero mutual influence as well as good overall performance. Besides an excellent potential for dual-sensing applications, the proposed sensor is a good candidate for application in mixing fluids and cell counting. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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3284 KiB

Open AccessArticle

A Digital Microfluidics Platform for Loop-Mediated Isothermal Amplification Detection

by Beatriz Jorge Coelho, Bruno Veigas, Hugo Águas, Elvira Fortunato, Rodrigo Martins, Pedro Viana Baptista and Rui Igreja

Sensors 2017, 17(11), 2616; https://doi.org/10.3390/s17112616 - 16 Nov 2017

Cited by 36 | Viewed by 8704

Abstract

Digital microfluidics (DMF) arises as the next step in the fast-evolving field of operation platforms for molecular diagnostics. Moreover, isothermal schemes, such as loop-mediated isothermal amplification (LAMP), allow for further simplification of amplification protocols. Integrating DMF with LAMP will be at the core [...] Read more.

Digital microfluidics (DMF) arises as the next step in the fast-evolving field of operation platforms for molecular diagnostics. Moreover, isothermal schemes, such as loop-mediated isothermal amplification (LAMP), allow for further simplification of amplification protocols. Integrating DMF with LAMP will be at the core of a new generation of detection devices for effective molecular diagnostics at point-of-care (POC), providing simple, fast, and automated nucleic acid amplification with exceptional integration capabilities. Here, we demonstrate for the first time the role of coupling DMF and LAMP, in a dedicated device that allows straightforward mixing of LAMP reagents and target DNA, as well as optimum temperature control (reaction droplets undergo a temperature variation of just 0.3 °C, for 65 °C at the bottom plate). This device is produced using low-temperature and low-cost production processes, adaptable to disposable and flexible substrates. DMF-LAMP is performed with enhanced sensitivity without compromising reaction efficacy or losing reliability and efficiency, by LAMP-amplifying 0.5 ng/µL of target DNA in just 45 min. Moreover, on-chip LAMP was performed in 1.5 µL, a considerably lower volume than standard bench-top reactions. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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3242 KiB

Open AccessArticle

Dual-Band Band-Pass Filter with Fixed Low Band and Fluidically-Tunable High Band

by Eiyong Park, Daecheon Lim and Sungjoon Lim

Sensors 2017, 17(8), 1884; https://doi.org/10.3390/s17081884 - 16 Aug 2017

Cited by 20 | Viewed by 6715

Abstract

In this work, we present a dual-band band-pass filter with fixed low-band resonant frequency and tunable high-band resonant frequency. The proposed filter consists of two split-ring resonators (SRRs) with a stub and microfluidic channels. The lower resonant frequency is determined by the length [...] Read more.

In this work, we present a dual-band band-pass filter with fixed low-band resonant frequency and tunable high-band resonant frequency. The proposed filter consists of two split-ring resonators (SRRs) with a stub and microfluidic channels. The lower resonant frequency is determined by the length of the SRR alone, whereas the higher resonant frequency is determined by the lengths of the SRR and the stub. Using this characteristic, we fix the lower resonant frequency by fixing the SRR length and tune the higher resonant frequency by controlling the stub length by injecting liquid metal in the microfluidic channel. We fabricated the filter on a Duroid substrate. The microfluidic channel was made from polydimethylsiloxane (PDMS), and eutectic gallium–indium (EGaIn) was used as the liquid metal. This filter operates in two states—with, and without, the liquid metal. In the state without the liquid metal, the filter has resonant frequencies at 1.85 GHz and 3.06 GHz, with fractional bandwidths of 4.34% and 2.94%, respectively; and in the state with the liquid metal, it has resonant frequencies at 1.86 GHz and 2.98 GHz, with fractional bandwidths of 4.3% and 2.95%, respectively. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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Review

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25 pages, 8965 KiB

Open AccessReview

Review of Recent Metamaterial Microfluidic Sensors

by Ahmed Salim and Sungjoon Lim

Sensors 2018, 18(1), 232; https://doi.org/10.3390/s18010232 - 15 Jan 2018

Cited by 172 | Viewed by 16563

Abstract

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require [...] Read more.

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter–nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological) sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range) with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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3389 KiB

Open AccessReview

Studying Electrotaxis in Microfluidic Devices

by Yung-Shin Sun

Sensors 2017, 17(9), 2048; https://doi.org/10.3390/s17092048 - 7 Sep 2017

Cited by 25 | Viewed by 8759

Abstract

Collective cell migration is important in various physiological processes such as morphogenesis, cancer metastasis and cell regeneration. Such migration can be induced and guided by different chemical and physical cues. Electrotaxis, referring to the directional migration of adherent cells under stimulus of electric [...] Read more.

Collective cell migration is important in various physiological processes such as morphogenesis, cancer metastasis and cell regeneration. Such migration can be induced and guided by different chemical and physical cues. Electrotaxis, referring to the directional migration of adherent cells under stimulus of electric fields, is believed to be highly involved in the wound-healing process. Electrotactic experiments are conventionally conducted in Petri dishes or cover glasses wherein cells are cultured and electric fields are applied. However, these devices suffer from evaporation of the culture medium, non-uniformity of electric fields and low throughput. To overcome these drawbacks, micro-fabricated devices composed of micro-channels and fluidic components have lately been applied to electrotactic studies. Microfluidic devices are capable of providing cells with a precise micro-environment including pH, nutrition, temperature and various stimuli. Therefore, with the advantages of reduced cell/reagent consumption, reduced Joule heating and uniform and precise electric fields, microfluidic chips are perfect platforms for observing cell migration under applied electric fields. In this paper, I review recent developments in designing and fabricating microfluidic devices for studying electrotaxis, aiming to provide critical updates in this rapidly-growing, interdisciplinary field. Full article

(This article belongs to the Special Issue Microfluidic Sensors)

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