Showing papers on "Biochip published in 2022"

Plasmonic nanomaterials with responsive polymer hydrogels for sensing and actuation

Abstract: Plasmonic nanomaterials have become an integral part of numerous technologies, where they provide important functionalities spanning from extraction and harvesting of light in thin film optical devices to probing of molecular species and their interactions on biochip surfaces. More recently, we witness increasing research efforts devoted to a new class of plasmonic nanomaterials that allow for on-demand tuning of their properties by combining metallic nanostructures and responsive hydrogels. This review addresses this recently emerged vibrant field, which holds potential to expand the spectrum of possible applications and deliver functions that cannot be achieved by separate research in each of the respective fields. It aims at providing an overview of key principles, design rules, and current implementations of both responsive hydrogels and metallic nanostructures. We discuss important aspects that capitalize on the combination of responsive polymer networks with plasmonic nanostructures to perform rapid mechanical actuation and actively controlled nanoscale confinement of light associated with resonant amplification of its intensity. The latest advances towards the implementation of such responsive plasmonic nanomaterials are presented, particularly covering the field of plasmonic biosensing that utilizes refractometric measurements as well as plasmon-enhanced optical spectroscopy readout, optically driven miniature soft actuators, and light-fueled micromachines operating in an environment resembling biological systems.

Highly sensitive and selective surface plasmon resonance biosensor for the detection of SARS-CoV-2 spike S1 protein.

Abstract: The reality that the coronavirus disease 2019 (COVID-19) is still raging around the world and making a comeback with a strong presence has highlighted the need for rapid and sensitive quantitative detection methods of viral RNA, antibody and antigen for widespread tracking and screening applications. Surface plasmon resonance (SPR) detection technology has achieved rapid development and become a standard measurement method in the fields of biosensing, biomedicine, biochemistry and biopharmaceuticals due to its advantages of high sensitivity, fast response and no need for labelling. Here, we report a sandwiched structure-based SPR biosensor for detecting a specific viral antigen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1 protein. The sensor combines a Ti3C2-MXene nanosheet modified sensing platform and polydopamine (PDA)-Ag nanoparticle (AgNP)/anti-SARS-CoV-2 spike S1 protein nanoconjugate signal enhancers, exhibiting a wide linear range of 0.0001 to 1000 ng mL-1 with a low detection limit of 12 fg mL-1 (S/N = 3). In the analysis of artificial saliva and human serum samples, the proposed SPR biosensor exhibits good reproducibility and high specificity, which indicates its potential for application in complex bodily fluids. The exploitation of the MXene-based SPR biochip for recognizing the SARS-CoV-2 antigen provides an accessible and rapid way for COVID-19 diagnosis, and promotes the application of 2D nanomaterial-based sensing chips in clinical diagnosis and disease screening. Significantly, the proposed method possesses general applicability that can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available.

A dielectrophoresis-based microfluidic system having double-sided optimized 3D electrodes for label-free cancer cell separation with preserving cell viability

Abstract: Early detection of circulating tumor cells (CTCs) in a patient's blood is essential to accurate prognosis and effective cancer treatment monitoring. The methods used to detect and separate CTCs should have a high recovery rate and ensure cells viability for post-processing operations, such as cell culture and genetic analysis. In this paper, a novel dielectrophoresis (DEP)-based microfluidic system is presented for separating MDA-MB-231 cancer cells from various subtypes of WBCs with the practical cell viability approach. Three configurations for the sidewall electrodes are investigated to evaluate the separation performance. The simulation results based on the finite-element method show that semi-circular electrodes have the best performance with a recovery rate of nearly 95% under the same operational and geometric conditions. In this configuration, the maximum applied electric field (1.11 × 105 V/m) to separate MDA-MB-231 is lower than the threshold value for cell electroporation. Also, the Joule heating study in this configuration shows that the cells are not damaged in the fluid temperature gradient (equal to 1 K). We hope that such a complete and step-by-step design is suitable to achieve DEP-based applicable cell separation biochips.

Lys-AuNPs@MoS2 Nanocomposite Self-Assembled Microfluidic Immunoassay Biochip for Ultrasensitive Detection of Multiplex Biomarkers for Cardiovascular Diseases.

Abstract: The progression of cardiovascular diseases is accompanied by myocardial injury and necrosis, heart failure, and inflammatory response. Accordingly, ultrasensitive and rapid detection of multiple biomarkers plays a vital role in clinical diagnosis and timely treatment. Here, we developed a novel Lys-AuNPs@MoS2 nanocomposite self-assembled microfluidic immunoassay biochip with digital signal output and applied it to the simultaneous detection of multiple serum biomarkers including inflammatory factors and cardiovascular biomarkers, PCT, CRP, IL6, cTnI, cTnT, and NT-BNP, with high throughput and sensitivity. The digital output signal was collected in the solid phase on the chip surface with two-dimensional distribution of targets. Lys-AuNPs@MoS2 nanocomposites self-assembled biochips could simultaneously detect all six biomarkers in 60 samples in 40 min with detection limit of a few to tens of pg/mL for all serum biomarkers. The microfluidic biochip based on Lys-AuNPs@MoS2 nanocomposites provides a promising method in applications for clinical diagnosis.

Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation

Abstract: Recent technological advances in nanoscience and material designing have led to the development of point-of-care devices for biomolecule sensing and cancer diagnosis. In situ and portable sensing devices for bedside, diagnosis can effectively improve the patient's clinical outcomes and reduce the mortality rate. Detection of exosomal RNAs by immuno-biochip with increased sensitivity and specificity to diagnose cancer has raised the understanding of the tumor microenvironment and many other technology-based biosensing devices hold great promise for clinical innovations to conquer the unbeatable fort of cancer metastasis. Electrochemical biosensors are the most sensitive category of biomolecule detection sensors with significantly low concentrations down to the atomic level. In this sense, this review addresses the recent advances in cancer detection and diagnosis by developing significant biological sensing devices that are believed to have better sensing potential than existing facilities.

Fluorescent on-site detection of multiple pathogens using smartphone-based portable device with paper-based isothermal amplification chip

Abstract: The development of cost-effective, portable, and ease-of-use sensing system for on-site genetic diagnostics is highly desirable for pathogen screening and infectious disease diagnosis. This study develops (1) a paper-based biochip which is able to integrate the loop-mediated isothermal amplification (LAMP) protocols for simultaneous detection of Escherichia coli O157:H7, Salmonella spp., and Staphylococcus aureus, and (2) a stand-alone smartphone-based portable device which can control exactly 65 °C for isothermal amplification as well as collect and analyze the thus generated fluorescence signals. The reported sensing system has been successfully demonstrated for foodborne pathogen detection with a limit of detection of 2.8 × 10-5 ng μL-1. Spiked milk samples with concentration as low as 10 CFU mL-1 were successfully determined within 4 h, demonstrating the practicality of the reported sensing system in the fields. The reported sensing system featuring simplicity and reliability is ideally suited for genetic diagnostics in low resource settings.

Rapid and High‐Throughput SARS‐CoV‐2 RNA Detection without RNA Extraction and Amplification by Using a Microfluidic Biochip

Abstract: Abstract The ongoing outbreak of the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) has spread globally and poses a threat to public health and National economic development. Rapid and high‐throughput SARS‐CoV‐2 RNA detection without the need of RNA extraction and amplification remain a key challenge. In this study, a new SARS‐CoV‐2 RNA detection strategy using a microfluidic biochip for the rapid and ultrasensitive detection of SARS‐CoV‐2 without RNA extraction and amplification was developed. This new strategy takes advantage of the specific SARS‐CoV‐2 RNA and probe DNA reaction in the microfluidic channel, fluorescence signal regulation by nanomaterials, and accurate sample control by the microfluidic chip. It presents an ultralow limit of detection of 600 copies mL−1 in a large linear detection regime from 1 aM to 100 fM. Fifteen samples were simultaneously detected in 40 min without the need for RNA purification and amplification. The detection accuracy of the strategy was validated through quantitative reverse transcription polymerase chain reaction (qRT‐PCR), with a recovery of 99–113 %. Therefore, the SARS‐CoV‐2 RNA detection strategy proposed in this study can potentially be used for the quantitative diagnosis of viral infectious diseases.

Flow-Based Microfluidic Biochips With Distributed Channel Storage: Synthesis, Physical Design, and Wash Optimization

Abstract: System-architecture design optimization of flow-based microfluidic biochips has been extensively investigated over the past decade. Most of the prior work, however, is still based on chip architectures with dedicated storage units and this, not only limits the performance of biochips, but also increases their fabrication cost. To overcome this limitation, a distributed channel-storage architecture can be implemented, where fluid samples can be cached temporarily in flow channels instead of using a dedicated storage. This new concept of fluid storage, however, requires a careful arrangement of fluid samples to enable the channels to fulfill the dual functions of transportation and caching. Moreover, to avoid cross-contamination between different fluidic flows, wash operations are necessary to remove the residue left in flow channels. In this article, we formulate the first practical system level design and wash optimization problem for microfluidic biochips with distributed channel storage architecture, considering high-level synthesis, physical design, and wash optimization simultaneously, and present a top-down design flow to solve this problem systematically. Given the protocol of a biochemical application and the corresponding design requirements, our goal is to generate a chip architecture with low fabrication cost. Meanwhile the biochemical application can be executed efficiently with an optimized wash scheme. Experimental results on multiple benchmarks confirm that our approach leads to short completion time of biochemical applications, low chip cost, as well as high wash efficiency.

Adaptive Droplet Routing for MEDA Biochips via Deep Reinforcement Learning

Abstract: Digital microfluidic biochips (DMFBs) based on a micro-electrode-dot-array (MEDA) architecture provide fine-grained control and sensing of droplets in real-time. However, excessive actuation of microelectrodes in MEDA biochips can lead to charge trapping during bioassay execution, causing the failure of microelectrodes and erroneous bioassay outcomes. A recently proposed enhancement to MEDA allows run-time measurement of microelectrode health information, thereby enabling synthesis of adaptive routing strategies for droplets. However, existing synthesis solutions are computationally infeasible for large MEDA biochips that have been commercialized. In this paper, we propose a synthesis framework for adaptive droplet routing in MEDA biochips via deep reinforcement learning (DRL). The framework utilizes the real-time microelectrode health feedback to synthesize droplet routes that proactively minimize the likelihood of charge trapping. We show how the adaptive routing strategies can be synthesized using DRL. We implement the DRL agent, the MEDA simulation environment, and the bioassay scheduler using the OpenAI Gym environment. Our framework obtains adaptive routing policies efficiently for COVID-19 testing protocols on large arrays that reflect the sizes of commercial MEDA biochips available in the marketplace, significantly increasing probabilities of successful bioassay completion compared to existing methods.

Uniform Tumor Spheroids on Surface-Optimized Microfluidic Biochips for Reproducible Drug Screening and Personalized Medicine

Abstract: Spheroids are recognized for resembling the important characteristics of natural tumors in cancer research. However, the lack of controllability of the spheroid size, form, and density in conventional spheroid culture methods reduces the reproducibility and precision of bioassay results and the assessment of drug-dose responses in spheroids. Nonetheless, the accurate prediction of cellular responses to drug compounds is crucial for developing new efficient therapeutic agents and optimizing existing therapeutic strategies for personalized medicine. We developed a surface-optimized PDMS microfluidic biochip to produce uniform and homogenous multicellular spheroids in a reproducible manner. This platform is surface optimized with 10% bovine serum albumin (BSA) to provide cell-repellent properties. Therefore, weak cell-surface interactions lead to the promotion of cell self-aggregations and the production of compact and uniform spheroids. We used a lung cancer cell line (A549), a co-culture model of lung cancer cells (A549) with (primary human osteoblasts, and patient-derived spine metastases cells (BML, bone metastasis secondary to lung). We observed that the behavior of cells cultured in three-dimensional (3D) spheroids within this biochip platform more closely reflects in vivo-like cellular responses to a chemotherapeutic drug, Doxorubicin, rather than on 24-well plates (two-dimensional (2D) model). It was also observed that the co-culture and patient-derived spheroids exhibited resistance to anti-cancer drugs more than the mono-culture spheroids. The repeatability of drug test results in this optimized platform is the hallmark of the reproducibility of uniform spheroids on a chip. This surface-optimized biochip can be a reliable platform to generate homogenous and uniform spheroids to study and monitor the tumor microenvironment and for drug screening.

Uniformity of spheroid-on-chip by surface treatment of PDMS microfluidic platforms

Abstract: Spheroids have emerged as a more reliable model for drug screening when compared with 2D culture models. Microfluidic based biochips have many advantages over other 3D cell culture models for drug testing on spheroids, including precise control of the cellular microenvironment. The control of the cell adhesion to the surface is one of the most important challenges affecting the size and the geometry of the spheroids which could be controlled by appropriate surface engineering methods. We have studied the modification of the PDMS surface properties treated by applying different concentrations of the two anti-fouling coatings (BSA and Pluronic F-68). The desired treatment of PDMS surface effectively inhibits cell adhesion to the surface and promotes cells self-aggregations to form more uniform and healthy spheroids for a longer period of time. The microscopic observations with qualitative and quantitate data revealed that surface properties drastically affect the number of the spheroids formed on-chip and their geometry. We used human breast cancer cell line (MDA-MB-231-GFP) while the concentration of the chemical coatings and incubation time were adjusted. Proper repellent PDMS surfaces were provided with minimum cell attachment and facilitated spheroid formation when compared with non-treated PDMS. The results demonstrate fundamental and helpful patterns for microfluidic based cell culture applications to improve the quantity and quality of spheroid formation on-chip which are strongly manipulated by surface properties (i.e., morphology, roughness, wettability and etc.)

Early Predictor Tool of Disease Using Label-Free Liquid Biopsy-Based Platforms for Patient-Centric Healthcare

Abstract: Simple Summary We proposed a comprehensive early prediction tool based on liquid biopsy for the label-free phenotypic analysis of cell clusters from clinical samples (n = 31). Our custom algorithm analysis, combined with a microfluidic-based tumor model, was designed to assess and stratify cancer patients in a label-free, cost-effective, and user-friendly way. Multiple quantitative phenotypic parameters (cluster size, thickness, roughness, and thickness per area) were derived from the profiling of the patient-derived cell clusters. Our platform could distinguish healthy donors from pretreatment cancer patients with high sensitivity (91.16 ± 1.56%) and specificity (71.01 ± 9.95%). In addition, the ratio of normalized gray value to cluster size (RGVS) parameter was significantly correlated to treatment duration and cancer stage. In conclusion, our patient-centric, early prediction tool will allow the prognosis of patients in a relatively less invasive manner, which can help clinicians identify diseases or indicate the need for new treatment strategies. Abstract Cancer cells undergo phenotypic changes or mutations during treatment, making detecting protein-based or gene-based biomarkers challenging. Here, we used algorithmic analysis combined with patient-derived tumor models to derive an early prediction tool using patient-derived cell clusters from liquid biopsy (LIQBP) for cancer prognosis in a label-free manner. The LIQBP platform incorporated a customized microfluidic biochip that mimicked the tumor microenvironment to establish patient clusters, and extracted physical parameters from images of each sample, including size, thickness, roughness, and thickness per area (n = 31). Samples from healthy volunteers (n = 5) and cancer patients (pretreatment; n = 4) could be easily distinguished with high sensitivity (91.16 ± 1.56%) and specificity (71.01 ± 9.95%). Furthermore, we demonstrated that the multiple unique quantitative parameters reflected patient responses. Among these, the ratio of normalized gray value to cluster size (RGVS) was the most significant parameter correlated with cancer stage and treatment duration. Overall, our work presented a novel and less invasive approach for the label-free prediction of disease prognosis to identify patients who require adjustments to their treatment regime. We envisioned that such efforts would promote the management of personalized patient care conveniently and cost effectively.

Free-access optomechanical liquid probes using a twin-microbottle resonator

Abstract: Cavity optomechanics provides high-performance sensor technology, and the scheme is also applicable to liquid samples for biological and rheological applications. However, previously reported methods using fluidic capillary channels and liquid droplets are based on fixed-by-design structures and therefore do not allow an active free access to the samples. Here, we demonstrate an alternate technique using a probe-based architecture with a twin-microbottle resonator. The probe consists of two microbottle optomechanical resonators, where one bottle (for detection) is immersed in liquid and the other bottle (for readout) is placed in air, which retains excellent detection performance through the high optical Q (~107) of the readout bottle. The scheme allows the detection of thermomechanical motion of the detection bottle as well as optomechanical drive and frequency tracking with a phase-locked loop. This technique could lead to in situ metrology at the target location in arbitrary media and could be extended to ultrasensitive biochips and rheometers.

Ultrasensitive Detection of Biomarkers in a Color‐Switchable Microcavity‐Reactor Laser

Abstract: Early detection and diagnosis are vitally important in reducing the mortality rate of fatal diseases but require highly sensitive detection of biomarkers. Presently, detection methods with the highest sensitivity require in vitro processing, while in vivo compatible fluorescence detections require a much higher concentration of biomarkers or limit of detection (LOD). In this paper, a fundamentally new strategy for ultrasensitive detection based on color‐switchable lasing with a cavity‐enhanced reduction of LOD is demonstrated, down to 1.4 × 10−16 mg ml−1 for a quantitative detection, lower than both the fluorescence method and plasmonic enhanced method. For a qualitative or a yes/no type of detection, the LOD is as low as 10–17 mg ml−1. The approach in this work is based on a dye‐embedded, in vivo compatible, polystyrene‐sphere cavity, penetrable by biomarkers. A polystyrene sphere serves the dual roles of a laser cavity and an in vivo bio‐reactor, in which dye molecules react with a biomarker, reporting biomarker information through lasing signals. The cavity‐enhanced emission and lasing with only a single biomarker molecule per cavity allow improved visual distinguishability via color changes. Furthermore, when combined with a narrow‐band filter, the color‐switchable lasers act as an “on‐off” logic signal and can be integrated into multiplexing detection assay biochips.

All-printed point-of-care immunosensing biochip for one drop blood diagnostics.

Abstract: Designing and preparing a fast and easy-to-use immunosensing biochip are of great significance for clinical diagnosis and biomedical research. In particular, sensitive, specific, and early detection of biomarkers in trace samples promotes the application of point-of-care testing (POCT). Here, we demonstrate an all-printed immunosensing biochip with the characteristics of hydrodynamic enrichment and photonic crystal-enhanced fluorescence. Direct quantitative detection of cardiac biomarkers via one drop of blood is achieved in 10 min. After simulating the hydrodynamic behavior of one droplet serum on the printed assay, creatine kinase-MB (CK-MB) has been recognized and located on the photonic crystal arrays. Benefiting from the fluorescence enhancement effect, quantitative detection of CK-MB has been demonstrated from 0.01 ng ml-1 to 100 ng ml-1, which is superior to the conventional enzyme-linked immunosorbent assay (ELISA). This strategy provides a general and easy-to-use approach for fast quantitative detection of biomarkers, which would be improved further for portable clinical diagnostics and home medical monitoring.

CMOS based capacitive sensor matrix for characterizing and tracking of biological cells

Abstract: The characterization and tracking of biological cells using biosensors are necessary for many scientific fields, specifically cell culture monitoring. Capacitive sensors offer a great solution due to their ability to extract many features such as the biological cells' position, shape, and capacitance. Through this study, a CMOS-based biochip that consists of a matrix of capacitive sensors (CSM), utilizing a ring oscillator-based pixel readout circuit (PRC), is designed and simulated to track and characterize a single biological cell based on its aforementioned different features. The proposed biochip is simulated to characterize a single Hepatocellular carcinoma cell (HCC) and a single normal liver cell (NLC). COMSOL Multiphysics was used to extract the capacitance values of the HCC and NLC and test the CSM's performance at different distances from the analyte. The PRC's ability to detect the extracted capacitance values of the HCC and NLC is evaluated using Virtuoso Analog Design Environment. A novel algorithm is developed to animate and predict the location and shape of the tested biological cell depending on CSM's capacitance readings simultaneously using MATLAB R2022a script. The results of both models, the measured capacitance from CSM and the correlated frequency from the readout circuit, show the biochip's ability to characterize and distinguish between HCC and NLC.

High-efficiency microdrilling of glass by parallel transient and selective laser processing with spatial light modulator

Abstract: To use glass as the substrate material in next-generation large-scale integrations and biochips, the high-speed fabrication of high-aspect-ratio microholes is necessary. Transient and selective laser (TSL) processing significantly reduces the processing time per hole. To further improve the processing efficiency, parallel TSL processing using a spatial light modulator is proposed in this study. Two 100-µm depth holes are successfully machined in parallel, in 50 µs. Furthermore, the process control parameters are investigated through high-speed observation and the laser irradiation conditions required for processing are clarified. Parallel processing of three or more holes and depth control of each hole is expected to be realized in future.