Label-free plasmonic-based biosensing using a gold nanohole array chip coated with a wafer-scale deposited WS2 monolayer.

This paper reports the fabrication, testing and obtained performance of a plasmonic sensor employing a gold (Au) nanohole array chip coated with tungsten disulphide (WS2), which is then functionalized for the detection of protein-protein interactions. A key novelty is that the WS2 was deposited as a monoatomic layer using a wafer-scale synthesis method that successfully provided a film of both high quality and uniform thickness. The deposited WS2 film was transferred onto a Au nanohole array chip using a novel method and was subsequently functionalized with biotin. The final sensor was tested and it demonstrated efficient real-time and label-free plasmonic detection of biotin-streptavidin coupling. Specifically, compared to a standard (i.e. uncoated) Au nanohole-based sensor, our WS2-coated Au nanohole array boosted the spectral shift of the resonance wavelength by ∼190%, resulting in a 7.64-fold improvement of the limit of detection (LOD).

Low-Cost Method and Biochip for Measuring the Trans-Epithelial Electrical Resistance (TEER) of Esophageal Epithelium.

Trans-epithelial electrical resistance (TEER) is a good indicator of the barrier integrity of epithelial tissues and is often employed in biomedical research as an effective tool to assess ion transport and permeability of tight junctions. The Ussing chamber is the gold standard for measuring TEER of tissue specimens, but it has major drawbacks: it is a macroscopic method that requires a careful and labor intensive sample mounting protocol, allows a very limited viability for the mounted sample, has large parasitic components and low throughput as it cannot perform multiple simultaneous measurements, and this sophisticated and delicate apparatus has a relatively high cost. This paper demonstrates a low-cost home-made "sandwich ring" method which was used to measure the TEER of tissue specimens effectively. This method inspired the subsequent design of a biochip fabricated using standard soft lithography and laser engraving technologies, with which the TEER of pig epithelial tissues was measured. Moreover, it was possible to temporarily preserve the tissue specimens for days in the biochip and monitor the TEER continuously. Tissue responses after exposure tests to media of various pH values were also successfully recorded using the biochip. All these demonstrate that this biochip could be an effective, cheaper, and easier to use Ussing chamber substitute that may have relevant applications in clinical practice.

Microfluidic and Micromachined/MEMS Devices for Separation, Discrimination and Detection of Airborne Particles for Pollution Monitoring.

Most of the microfluidics-related literature describes devices handling liquids, with only a small part dealing with gas-based applications, and a much smaller number of papers are devoted to the separation and/or detection of airborne inorganic particles. This review is dedicated to this rather less known field which has become increasingly important in the last years due to the growing attention devoted to pollution monitoring and air quality assessment. After a brief introduction summarizing the main particulate matter (PM) classes and the need for their study, the paper reviews miniaturized devices and/or systems for separation, detection and quantitative assessment of PM concentration in air with portable and easy-to-use platforms. The PM separation methods are described first, followed by the key detection methods, namely optical (scattering) and electrical. The most important miniaturized reported realizations are analyzed, with special attention given to microfluidic and micromachined or micro-electro-mechanical systems (MEMS) chip-based implementations due to their inherent capability of being integrated in lab-on-chip (LOC) type of smart microsystems with increased functionalities that can be portable and are easy to use. The operating principles and (when available) key performance parameters of such devices are presented and compared, also highlighting their advantages and disadvantages. Finally, the most relevant conclusions are discussed in the last section.

An integrated on-chip platform for negative enrichment of tumour cells.

The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500µL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps.

Design and fabrication of Poly(dimethylsiloxane) arrayed waveguide grating.

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) arrayed waveguide grating (AWG) with four-channel output for operation in the visible light wavelength range. The PDMS AWG was realized based on the single-mode PDMS rib waveguide. The device was designed for 1 nm channel spacing with the wavelength ranging from 639 to 644 nm. The measured insertion loss is 11.4 dB at the peak transmission spectrum and the adjacent crosstalk is less than -16 dB. The AWG device occupies an area of 7.5 × 15 mm(2). PDMS AWG has the potential for integration with microfluidics in a monolithic PDMS lab-on-a-chip device for visible light spectroscopy applications.

Design and fabrication of poly(dimethylsiloxane) single-mode rib waveguide.

We have designed, fabricated and characterized poly(dimethylsiloxane) (PDMS) single-mode rib waveguides. PDMS was chosen specifically for the core and cladding. Combined with the soft lithography fabrication techniques, it enables an easy integration of microoptical components for lab-on-a-chip systems. The refractive index contrast, of 0.07% between the core and cladding for single-mode propagation was achieved by modifying the properties of the same base material. Alternatively, a higher refractive index contrast, of 1.18% was shown by using PDMS materials from two different manufacturers. The fabricated rib waveguides were characterized for mode profile characteristics and confirmed the excitation of the fundamental mode of the waveguide. The propagation loss of the single-mode rib waveguide was characterized using the cutback measurement method at a wavelength of 635 nm and found to be 0.48 dB/cm for of 0.07% and 0.20 dB/cm for of 1.18%. Y-branch splitter of PDMS single-mode rib waveguide was further demonstrated.

Algorithm and simulation for analysis of bio-images obtained by aperture diffraction based optical MEMS.

This paper proposes a novel method to detect transparent living cells in a transparent microfluidic chamber by optical diffraction of an aperture or an aperture array. Through the analysis of the far-field diffraction pattern, one of the parameters of the cells, including the size, refractive index, or position, can be extracted by the analysis software developed in this paper. Calculations are carried out to discuss the key issues of this MEMS device, and our simulation is verified by diffraction patterns of transparent microparticles on fabricated apertures, recorded via a digital camera.

Design of MEMS devices with optical apertures for the detection of transparent biological cells.

This paper provides a novel technique to detect transparent biological living cells trapped in a microfluidic MEMS device by optical diffraction. The device essentially consists of an optical aperture or an aperture array patterned in metal layer and a microfluidic chamber positioned above the center of the aperture. When the cells in the chamber are illuminated through the aperture, the far-field diffraction pattern can be recorded by a CCD camera or a photodetector array. This diffraction pattern uniquely corresponds to the sizes, positions, and intrinsic optical properties of the aperture, cells, and the microfluidic chamber materials, so any unknown but relevant parameter is able to be extrapolated when all other parameters are fixed or identified. This paper describes in detail the designs of various microfluidic chambers and apertures for this application, and the development of a complete set of software for the analysis of the cells' optical properties. Compared with other currently available methods for the detection of transparent living cells, this method has the advantages of simple device structure, easy to manipulate, able to simultaneously detect several cells of different species, as well as providing accurate and sensitive results. Besides the detection of living cells, this technique can also be used to detect or characterize other transparent or low optical absorption particles, such as polymer spheres or insoluble droplets, inside an aqueous solution.