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Abstract This review reports diverse microfluidic systems utilizing surface-enhanced Raman scattering (SERS) detection for disease diagnosis. Integrating SERS detection technology, providing high-sensitivity detection, and microfluidic technology for manipulating small liquid samples in microdevices has expanded the analytical capabilities previously confined to larger settings. This study explores the principles and uses of various SERS-based microfluidic devices developed over the last two decades. Specifically, we investigate the operational principles of documented SERS-based microfluidic devices, including continuous-flow channels, microarray-embedded microfluidic channels, droplet microfluidic channels, digital droplet channels, and gradient microfluidic channels. We also examine their applications in biomedical diagnostics. In conclusion, we summarize the areas requiring further development to translate these SERS-based microfluidic technologies into practical applications in clinical diagnostics.

This review reports diverse microfluidic systems utilizing surface-enhanced Raman scattering (SERS) detection for disease diagnosis. Integrating SERS detection technology, providing high-sensitivity detection, and microfluidic technology for manipulating small liquid samples in microdevices has expanded the analytical capabilities previously confined to larger settings. This study explores the principles and uses of various SERS-based microfluidic devices developed over the last two decades. Specifically, we investigate the operational principles of documented SERS-based microfluidic devices, including continuous-flow channels, microarray-embedded microfluidic channels, droplet microfluidic channels, digital droplet channels, and gradient microfluidic channels. We also examine their applications in biomedical diagnostics. In conclusion, we summarize the areas requiring further development to translate these SERS-based microfluidic technologies into practical applications in clinical diagnostics. [ABSTRACT FROM AUTHOR]

On-chip multi-dimensional detection systems integrating pixelated polarization and spectral filter arrays are the latest trend in optical detection instruments, showing broad application potential for diagnostic medical imaging and remote sensing. However, thin-film or microstructure-based filter arrays typically have a trade-off between the detection dimension, optical efficiency, and spectral resolution. Here, we demonstrate novel on-chip integrated polarization spectral detection filter arrays consisting of metasurfaces and multilayer films. The metasurfaces with two nanopillars in one supercell are designed to modulate the Jones matrix for polarization selection. The angle of diffraction of the metasurfaces and the optical Fabry–Perot (FP) cavities determine the spectrum's center wavelength. The polarization spectral filter arrays are placed on top of the CMOS sensor; each array corresponds to one pixel, resulting in high spectral resolution and optical efficiency in the selected polarization state. To verify the methodology, we designed nine-channel polarized spectral filter arrays in a wavelength range of 1350 nm to 1550 nm for transverse electric (TE) linear polarization. The array has a 10 nm balanced spectral resolution and average peak transmission efficiency of over 75%, which is maintained by utilizing lossless dielectric material. The proposed array can be fabricated using overlay e-beam lithography, and the process is CMOS-compatible. The proposed array enables broader applications of in situ on-chip polarization spectral detection with high efficiency and spectral resolution, as well as in vivo imaging systems. [ABSTRACT FROM AUTHOR]

On-chip multi-dimensional detection systems integrating pixelated polarization and spectral filter arrays are the latest trend in optical detection instruments, showing broad application potential for diagnostic medical imaging and remote sensing. However, thin-film or microstructure-based filter arrays typically have a trade-off between the detection dimension, optical efficiency, and spectral resolution. Here, we demonstrate novel on-chip integrated polarization spectral detection filter arrays consisting of metasurfaces and multilayer films. The metasurfaces with two nanopillars in one supercell are designed to modulate the Jones matrix for polarization selection. The angle of diffraction of the metasurfaces and the optical Fabry–Perot (FP) cavities determine the spectrum’s center wavelength. The polarization spectral filter arrays are placed on top of the CMOS sensor; each array corresponds to one pixel, resulting in high spectral resolution and optical efficiency in the selected polarization state. To verify the methodology, we designed nine-channel polarized spectral filter arrays in a wavelength range of 1350 nm to 1550 nm for transverse electric (TE) linear polarization. The array has a 10 nm balanced spectral resolution and average peak transmission efficiency of over 75%, which is maintained by utilizing lossless dielectric material. The proposed array can be fabricated using overlay e-beam lithography, and the process is CMOS-compatible. The proposed array enables broader applications of in situ on-chip polarization spectral detection with high efficiency and spectral resolution, as well as in vivo imaging systems.

Field-programmable gate arrays (FPGAs) are integrated circuits (ICs) that can be reconfigured to the desired functionalities, without manufacturing dedicated chips. Due to their programmable nature, FPGAs have been prevalent in the large majority of modern systems. This raises high demands for verifying the security of circuit implementations on FPGAs, since they are vulnerable to hardware trojans (HTs) that can be inserted through modified configuration files. In this article, we propose an on-chip security framework to ensure the trustworthiness of circuit implementations on FPGAs at runtime. The core of the framework is a time-to-digital converter (TDC)-based hardware security primitive that can be predeployed on FPGAs to verify whether the FPGA-based designs are tampered with or corrupted by HTs. The parameter-adjustable TDC sensor, which is the primary component of the primitive, is carefully designed, adjusted, and implemented, thus the TDC sensor can monitor the transient voltage fluctuations within FPGAs with a high resolution. Versus statistical data analysis, tiny abnormal variations introduced by the Trojan insertion and activation are distinguished. Experimental results on Xilinx Spartan-6 FPGAs demonstrate the effectiveness of the proposed TDC-based on-chip trust evaluation framework and HT detection method. [ABSTRACT FROM AUTHOR]

A false negative result is one of the major problems in nucleic acid detection. Failure to screen positive samples for pathogens or viruses poses a risk to public health. This situation will lead to more serious consequences for infectious pathogens or viruses. At present, the common solution is to introduce exogenous or endogenous internal control. Because it amplifies and is detected separately from the target gene, it cannot avoid false negative results caused by DNA extraction failure or reagent inactivation. There is an urgent need for a simple and reliable method to solve the false negative problem of nucleic acid detection. We established a chip and an on-chip detection method for the integrated detection of target genes and internal control using the CRISPR system in LAMP amplification products. The chip is processed from a low-cost PMMA board and has three chambers and some channels. After adding the sample, the chip only needs to be rotated twice, and the sample enters three chambers successively depending on its gravity for dual LAMP reaction and CRISPR detections. With a portable LED blue light exciter, visual fluorescence detection is realized. Whether the detection result is positive, negative, or invalid can be determined according to the fluorescence in the CRISPR chamber for target gene and CRISPR chamber for internal control. In this study, the detection of Salmonella enterica in Fenneropenaeus chinensis was taken as an example. The results showed good specificity and sensitivity. It could detect as low as 15 copies/μL of Salmonella enterica. The on-chip detection solves the problem of aerosol contamination and false negative results. It has the advantages of high sensitivity, high specificity, high accuracy, and low cost. This research will advance the development of nucleic acid detection technology, providing a new and reliable strategy for POCT detection of pathogenic bacteria and viruses. [Display omitted] • A nucleic acid detection method and a corresponding chip are developed. • Problems of aerosol pollution and false negative results are solved. • The integrated chip is portable, simple in structure and low in cost. • The on-chip detection integrates amplification and pseudo dual gene detection. • As low as 15 copies/μL of Salmonella can be detected by visible fluorescence. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD), Parkinson’s disease (PD) and glaucoma are all regarded as neurodegenerative diseases (neuro-DDs) because these diseases are highly related to the degeneration loss of functions and death of neurons with aging. The conventional diagnostic methods such as neuroimaging for these diseases are not only expensive but also time-consuming, resulting in significant financial burdens for patients and public health challenge for nations around the world. Hence early detection of neuro-DDs in a cost-effective and rapid manner is critically needed. For the past decades, some chip-based detection technologies have been developed to address this challenge, showing great potential in achieving point-of-care (POC) diagnostics of neuro-DDs. In this review, chip-based detection of neuro-DDs’ biomarkers enabled by different transducing mechanisms is evaluated.

In this paper we present a compact technological demonstrator including on the same glass substrate an electrowetting-on-dielectrics (EWOD) system, a linear array of amorphous silicon photosensor and a capillary-driven microfluidic channel. The proposed system comprises also a compact modular electronics controlling the digital microfluidics through the USB interface of a computer. The system provides therefore both on-chip detection and microfluidic handling needed for the realization of a ‘true’ Lab-on-Chip. The geometry of the photosensors has been designed to maximize the radiation impinging on the photosensor and to minimize the inter-site crosstalk, while the fabrication process has been optimized taking into account the compatibility of all the technological steps for the fabrication of the EWOD system, the photosensor array and the microfluidics channels. As a proof of the successful integration of the different technological steps we demonstrated the ability of the a-Si:H photosensors to detect the presence of a droplet over an EWOD electrode and the effective coupling between the digital and the continuous microfluidics, that can allow for functionalization, immobilization and recognition of biomolecules without external optical devices or microfluidic interconnections.

Abstract: We demonstrate the integration of DNA amplification and detection functionalities developed on a lab‐on‐a‐chip microdevice utilizing solid‐phase polymerase chain reaction (SP‐PCR) for point‐of‐need (PON) DNA analyses. First, the polycarbonate microdevice was fabricated by thermal bonding  to contain microchambers as reservoirs for performing SP‐PCR. Next, the microchambers were subsequently modified with polyethyleneimine and glutaraldehyde for immobilizing amine‐modified forward primers. During SP‐PCR, the immobilized forward primers and freely diffusing fluorescence‐labeled reverse primers cooperated to generate target amplicons, which remained covalently attached to the microchambers for the fluorescence detection. The SP‐PCR microdevice was used for the direct identifications of two widely detected foodborne pathogens, namely Salmonella spp. and Staphylococcus aureus, and an alga causing harmful algal blooms annually in South Korea, Cochlodinium polykrikoides. The SP‐PCR microdevice would be versatilely applied in PON testing as a universal platform for the fast identification of foodborne pathogens and environmentally threatening biogenic targets. [ABSTRACT FROM AUTHOR]

Cefepime is an important fourth-generation cephalosporin, having a broad antimicrobial spectrum. This article describes a new application of microfabricated chip with integrated Pt microelectrodes, for the electrochemical detection (ECD) of cefepime. In this analysis, electro-oxidation of cefepime was investigated on an unmodified Pt microelectrode in acetate buffer at pH 4.5. Differential pulse voltammetry (DPV) along with cyclic voltammetry (CV) was performed as a major read out technique. With this method, a linear calibration curve for 25-150 μM with a limit of detection of 15 μM was obtained. This investigation presents a simple methodology and rapid results that, within the above calibration range, can be obtained without any pretreatment of the analyte. [ABSTRACT FROM AUTHOR]

Abstract: Double detection of microsphere light scattering and quantum dot emission was demonstrated for lab-on-a-chip immunoassay without using stationary support. We conjugated quantum dots (QDs) onto microspheres to enable multiplex assays as well as to enhance the limit of detection (LOD). We named this configuration “nano-on-micro” or “NOM”. Upon radiation with UV light (380nm), a stronger light scattering signal is observed with NOMs than QDs or microspheres alone. Additionally, NOMs are easier to handle than QDs. Since QDs also provide fluorescent emission, we are able to utilize an increase in light scattering for detecting antigen–antibody reaction and a decrease in QD emission to identify which antibody (or antigen) is present. Two types of NOM combinations were used. One batch of microspheres was coated with QDs emitting at 655nm and mouse IgG (mIgG); the other with QDs emitting at 605nm and bovine serum albumin (BSA). A mixture of these two NOMs was used to identify either anti-mIgG or anti-BSA. NOM particles and target solutions were mixed in a microfluidic device (using highly carboxylated microspheres as previously demonstrated by our group) and on-chip detection was performed using proximity optical fibers. Forward light scattering at 380nm was collected. With the positive target, the scattering signal was increased. The LOD was as low as 50ngml−1 (330 pM) with p <0.05. Fluorescent emission (655 or 605nm) was simultaneously collected. With the positive target, the emission signal was attenuated. Therefore, we were able to detect two different antibodies simultaneously with two different detection protocols. We believe this NOM bioassay has the ability to screen for and detect multiple antibodies with minimal sample processing and handling (one-step lab-on-a-chip immunoassay). [Copyright &y& Elsevier]

• Microfluidic-based microextraction was combined with smartphone-based detection. • An on-chip sensing strategy was introduced using a smartphone. • The copper assay was performed by the method successfully. • The method was used for the analysis of biological, environmental, and food samples. • The method was simple and cost-effective with adequate analytical performance. In the present work, a simple and green microfluidic-based liquid-liquid microextraction in combination with smartphone-based on-chip detection was introduced for the determination of copper in environmental, biological, and food samples. The procedure was based on an ion-pair formation between tetrabutylammonium and tetrathiocyanatocuprate(II) anion, which was extracted with a suitable extractant and subsequent color sensing using a smartphone. All the steps were performed in a microchip. The smartphone was used as both a detector and a data processing unit. Different experimental parameters affecting analytical signal were studied and optimized. Under the optimum conditions, the method showed a linear dynamic range between 0.3 and 40 mg L−1 with a determination coefficient of 0.9953. The limits of detection and quantification were obtained 0.1 and 0.3 mg L−1, respectively. The method provided a precise determination with relative standard deviations in the range of 4.1–5.3%. Finally, the method was successfully applied for the determination of copper in whole blood, mushroom, wastewater, and tap water samples with spiking recoveries in the ranges of 80–98%, 96–108%, 95–107%, and 100–103%, respectively. In comparison with the atomic absorption technique, no significant difference was observed between the two methods in terms of accuracy. [ABSTRACT FROM AUTHOR]

Scattering-based on-chip excitation and detection on the arrayed-waveguide platform has been developed and implemented. Detected signals were processed with the proposed multiplication-based cross-correlation algorithm. The algorithm is capable of not only achieving signal enhancement (80 dB relative to the untreated signals) but also velocity measurement. Thus, particles flowing at different speed could also be accurately detected. Processed signals were verified by comparison to frame-by-frame video images, showing excellent correspondence. The signal processing algorithm can be easily extended to real-time on-chip detection [ABSTRACT FROM PUBLISHER]

Alzheimer's disease (AD), Parkinson's disease (PD) and glaucoma are all regarded as neurodegenerative diseases (neuro-DDs) because these diseases are highly related to the degeneration loss of functions and death of neurons with aging. The conventional diagnostic methods such as neuroimaging for these diseases are not only expensive but also time-consuming, resulting in significant financial burdens for patients and public health challenge for nations around the world. Hence early detection of neuro-DDs in a cost-effective and rapid manner is critically needed. For the past decades, some chip-based detection technologies have been developed to address this challenge, showing great potential in achieving point-of-care (POC) diagnostics of neuro-DDs. In this review, chip-based detection of neuro-DDs' biomarkers enabled by different transducing mechanisms is evaluated. [ABSTRACT FROM AUTHOR]