Optical Properties of Tetrahedral Amorphous Carbon Films and Their Potential for Lab-on-a-Chip

In this study, tetrahedral amorphous carbon (ta-C) films with thicknesses between several 100 nm and several micrometers have been deposited onto polished tungsten carbide and steel substrates by pulsed laser deposition (PLD) using an excimer laser (248 nm wavelength). We investigate the optical properties (e.g. the refractive index (n) and extinction coefficient (k) in the visible and near-infrared wavelength range) of these layers in dependence of the used laser ablation fluence on the target. It is shown that n of ~2000 nm thick ta-C films can be tuned, depending on the sp3-content, between n = 2.5 and 2.8 at a wavelength of 632 nm. Besides of this k reduces with the sp3-content and is as low as 0.03 at sp3-contents of more than 75%. We proof that this gives the opportunity to prepare coating with tailored optical properties. Furthermore, it is shown that the ta-C films have low background fluorescence in the wavelengths range of 380 - 750 nm, which make this thin films attractive for certain optical, medical and biotechnological applications. We present for the first time that one possible application is the use in Lab-on-a-Chip-systems (LOC). Within these systems, the ultrasensitive detection of fluorescence markers and dyes is a challenge. In order to increase the signal-to-noise-ratio, a setup was developed, that used the specific optical properties of ta-C films produced by PLD. We used the ta-C film as an integrated reflector that combined low background fluorescence, a low reflectivity at the excitation wavelength and the high reflectivity at the emission wavelength. We prove that this setup improves the detection of fluorescence photons.

Additive nanomanufacturing of lab-on-a-chip fluorescent peptide nanoparticle arrays for Alzheimer＇s disease diagnosis

This paper proposes an additive nanomanufacturing approach to fabricate a personalized lab-on-a-chip fluorescent peptide nanoparticles （f-PNPs） array for simultaneous multi-biomarker detection that can be used in Alzheimer＇s disease （AD） diagnosis. We will discuss optimization techniques for the additive nanomanufacturing process in terms of reliability, yield and manufacturing efficiency. One contribution of this paper lies in utilization of additive nanomanufacturing techniques to fabricate a patient-specific customize-designed lab-on-a-chip device for personalized AD diagnosis, which remains a major challenge for biomedical engineering. Through the integrated bio-design and bio-manufacturing process, doctor＇s check- up and computer-aided customized design are integrated into the lab-on-a-chip array for patient-specific AD diagnosis. In addition, f-PNPs with targeting moieties for personalized AD biomarkers will be self-assembled onto the customized lab-on-a- chip through the additive nanomanufacturing process, which has not been done before. Another contribution of this research is the personalized lab-on-a-chip f-PNPs array for AD diagnosis utilizing limited human blood. Blood-based AD assessment has been described as ＂the holy grail＂ of early AD detection. This research created the computer-aided design, fabrication through additive nanomanufacturing, and validation of the f-PNPs array for AD diagnosis. This is a highly interdisciplinary research contributing to nanotechnology, biomaterials, and biomedical engineering for neurodegenerative disease. The conceptual work is preliminary with intent to introduce novel techniques to the application. Large-scale manufacturing based on the proposed framework requires extensive validation and optimization.

A Smart Procedure for the Femtosecond Laser-Based Fabrication of a Polymeric Lab-on-a-Chip for Capturing Tumor Cell

Rapid prototyping methods for the design and fabrication of polymeric labs-on-a-chip are on the rise,as they allow high degrees of precision and flexibility.For example,a microfluidic platform may require an optimization phase in which it could be necessary to continuously modify the architecture and geometry;however,this is only possible if easy,controllable fabrication methods and low-cost materials are available.In this paper,we describe the realization process of a microfluidic tool,from the computer-aided design(CAD)to the proof-of-concept application as a capture device for circulating tumor cells(CTCs).The entire platform was realized in polymethyl methacrylate(PMMA),combining femtosecond(fs)laser and micromilling fabrication technologies.The multilayer device was assembled through a facile and low-cost solvent-assisted method.A serpentine microchannel was then directly biofunctionalized by immobilizing capture probes able to distinguish cancer from non-cancer cells without labeling.The low material costs,customizable methods,and biological application of the realized platform make it a suitable model for industrial exploitation and applications at the point of care.

Operando investigation of particle re-entrainment mechanism in electrostatic capture process on the lab-on-a-chip

Inhalable particle is a harmful air pollutant that causes a significant threat to people's health and ecological environments,which should be removed to purify air,but there exists limited removal efficiency due to particle re-entrainment.Here,Operando observation system based on microscopic visualization method is developed to make in situ test of particle migration,deposition and re-entrainment characteristics on a lab-on-a-chip to achieve the investigation in micro-level scale.The deposition evolution of charged particles is recorded in electric field region intuitively,which confirms the fracture of particle chain occurs during the growth process of deposited particles.It captures the instantaneous process that a larger particle with micron size due to the coagulation of submicron particles fractures from main body of the particle chain for the first time.The analysis of migration behavior of a single submicron particle near electrode surface demonstrates the direct influence of drag force on the fracture of particle chain.This work is the first-time visualization of dynamic process and mechanism elucidation of particle re-entrainment at the micron level,and the findings will provide the theory support for the particle re-entrainment mechanism and bring inspires of enhancing capture efficiency of inhalable particle.

Artificial intelligence-motivated in-situ imaging for visualization investigation of submicron particles deposition in electric-flow coupled fields

This study delves into the intricate deposition dynamics of submicron particles within electric-flow coupled fields,underscoring the unique challenges posed by their minuscule size,aggregation tendencies,and biological reactivity.Employing an operando investigation system that synergizes microfluidic technology with advanced micro-visualization techniques within a lab-on-a-chip framework enables a meticulous examination of the dynamic deposition phenomena.The incorporation of object detection and deep learning methodologies in image processing streamlines the automatic identification and swift extraction of crucial data,effectively tackling the complexities associated with capturing and mitigating these hazardous particles.Combined with the analysis of the growth behavior of particle chain under different applied voltages,it established that a linear relationship exists between the applied voltage and θ.And there is a negative correlation between the average particle chain length and electric field strength at the collection electrode surface(4.2×10^(5)to 1.6×10^(6)V·m^(-1)).The morphology of the deposited particle agglomerate at different electric field strengths is proposed:dendritic agglomerate,long chain agglomerate,and short chain agglomerate.

Biomimetic Infiltrating Surface Construction Based on Micro and Nano Structures

Microfluidic chips hold significant potential for applications in various fields, such as biological analysis, chemical separation, and drug screening. Here, we draw inspiration from the natural ability of aquatic plants to capture different substances in streams, focusing on the design and fabrication of surfaces with micron and nano-scale structures to mimic the wetting phenomenon observed in nature, thereby achieving the capture and separation of specific substances. This paper reports on the self-assembly of magnetic nanoparticles, the preparation of flexible magnetic nano-chains, and the modification of microfluidic chip surfaces, providing a novel perspective and approach to microfluidic chip technology.

生物芯片──二十一世纪革命性的技术

Biochip is a kind of minimized and integrated analyzer for molecular biology and biochemistry. Advances in biochip technology enable massive parallel mining of biological data, with biochips providing hybridizationbased expression monitoring, polymorphism detection and genotyping on a genomic scale. Microarrays may soon permit the expression analysis of the entire human genome in a single reaction. These ’genome chips’ will provide access to key areas of human health, including disease diagnosis, drug discovery, toxicology, etc. Microarray technology is rapidly becoming a central platform for functional genomics. Development of biochips is to immigrate the eatire analysis process of biochemical reactions and establish the micro total analytical system or lab-on-a-chip.

3D printed microfluidic devices:a review focused on four fundamental manufacturing approaches and implications on the field of healthcare

In the last fewyears,3D printing has emerged as a promising alternative for the fabrication ofmicrofluidic devices,overcoming some of the limitations associated with conventional soft-lithography.Stereolithography(SLA),extrusion-based technology,and inkjet 3D printing are three of the widely used 3D printing technologies owing to their accessibility and affordability.Microfluidic devices can be 3D printed by employing a manufacturing approach from four fundamental manufacturing approaches classified as(1)direct printing approach,(2)mold-based approach,(3)modular approach,and(4)hybrid approach.To evaluate the feasibility of 3D printing technologies for fabricating microfluidic devices,a review focused on 3D printing fundamental manufacturing approaches has been presented.Using a broad spectrum of additive manufacturing materials,3D printed microfluidic devices have been implemented in various fields,including biological,chemical,and material synthesis.However,some crucial challenges are associated with the same,including low resolution,low optical transparency,cytotoxicity,high surface roughness,autofluorescence,non-compatibility with conventional sterilization methods,and low gas permeability.The recent research progress in materials related to additive manufacturing has aided in overcoming some of these challenges.Lastly,we outline possible implications of 3D printed microfluidics on the various fields of healthcare such as in vitro disease modeling and organ modeling,novel drug development,personalized treatment for cancer,and cancer drug screening by discussing the current state and future outlook of 3D printed‘organs-on-chips,’and 3D printed‘tumor-on-chips.’We conclude the review by highlighting future research directions in this field.

Progress of Microfluidics for Biology and Medicine

Microfluidics has been considered as a potential technology to miniaturize the conventional equipments and technologies. It offers advantages in terms of small volume, low cost, short reaction time and highthroughput. The applications in biology and medicine research and related areas are almost the most extensive and profound. With the appropriate scale that matches the scales of cells, microfluidics is well positioned to contribute significantly to cell biology. Cell culture, fusion and apoptosis were successfully performed in microfluidics. Microfluidics provides unique opportunities for rare circulating tumor cells isolation and detection from the blood of patients, which furthers the discovery of cancer stem cell biomarkers and expands the understanding of the biology of metastasis. Nucleic acid amplification in microfluidics has extended to single-molecule, high-throughput and integration treatment in one chip. DNA computer which is based on the computational model of DNA biochemical reaction will come into practice from concept in the future. In addition, microfluidics offers a versatile platform for protein-protein interactions, protein crystallization and high-throughput screening. Although microfluidics is still in its infancy, its great potential has already been demonstrated and will provide novel solutions to the high-throughput applications.

Photoic crystal nanobeam cavity devices for on-chip integrated silicon photonics

Integrated circuit(IC)industry has fully considered the fact that the Moore’s Law is slowing down or ending.Alternative solutions are highly and urgently desired to break the physical size limits in the More-than-Moore era.Integrated silicon photonics technology exhibits distinguished potential to achieve faster operation speed,less power dissipation,and lower cost in IC industry,because their COMS compatibility,fast response,and high monolithic integration capability.Particularly,compared with other on-chip resonators(e.g.microrings,2D photonic crystal cavities)silicon-on-insulator(SOI)-based photonic crystal nanobeam cavity(PCNC)has emerged as a promising platform for on-chip integration,due to their attractive properties of ultra-high Q/V,ultra-compact footprints and convenient integration with silicon bus-waveguides.In this paper,we present a comprehensive review on recent progress of on-chip PCNC devices for lasing,modulation,switching/filting and label-free sensing,etc.

Design of interdigitated transducers for acoustofluidic applications

Interdigitated transducers(IDTs)were originally designed as delay lines for radars.Half a century later,they have found new life as actuators for microfluidic systems.By generating strong acoustic fields,they trigger nonlinear effects that enable pumping and mixing of fluids,and moving particles without contact.However,the transition from signal processing to actuators comes with a range of challenges concerning power density and spatial resolution that have spurred exciting developments in solid-state acoustics and especially in IDT design.Assuming some familiarity with acoustofluidics,this paper aims to provide a tutorial for IDT design and characterization for the purpose of acoustofluidic actuation.It is targeted at a diverse audience of researchers in various fields,including fluid mechanics,acoustics,and microelectronics.

Microfluidics:Emerging prospects for anti-cancer drug screening

Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.

Micro Flow-Through Thermocycler with Simple Meandering Channel with Symmetric Temperature Zones for Disposable PCR-Devices in Microscope Slide Format

Chip-based flow-through PCR implements the PCR as a continuous process for nucleic acid analytics. The sample is transported in a winding channel through temperature zones required for denaturation, annealing and extension. Main fields of application are the monitoring of continuous processes for rapid identification of contaminants and quality control as well as high throughput screening of cells or microorganisms. A modular arrangement with five heating zones for flow-through PCR is discussed and evaluated. The special heater arrangement allows the implementation of up to 40 cycles on the footprint of a microscope slide, which is placed on top ofa 5 zones heating plate. Liquid/liquid two phase flow of PCR reaction mixture and mineral oil have been applied to create a segmented flow process scheme. In that way, the developed system may provide flow-through PCR as a unit operation for the droplet based microfluidics platform. The single use of disposable devices is commonly preferred due to the sensitivity of the PCR process to contaminations. All-glass microfluidic chips and disposable chip devices, made from polycarbonate as a replication with identically geometry, have been fabricated and tested. For the first time, microchannel geometries with nearly circular profile developed by all-glass technology have been transferred to mass fabrication by injection compression molding. Both devices have been successfully applied for the detection of the tumor suppressor gene p53. Although product yield and selectivity of the amplification process do not depend on the chip material, a well defined, reliable segmented flow regime could only be realized in the all-glass chip.

DETECTION AND APPLICATION OF MICROFLUIDIC ISOTHERMAL AMPLIFICATION ON CHIP

Loop-mediated isothermal amplification(LAMP)is a novel nucleic acid amplification method.Compared with the widely utilized polymerase chain reaction(PCR),LAMP has higher speed and efficiency as well as lower requirement for system temperature control because the whole amplification process is isothermal and no efforts are needed to switch between different temperatures.In this paper,we designed and fabricated different kinds of polycarbonate(PC)microfluid chips,explored appropriate reaction condition for LAMP in microenvironment(1 nL→10μL),and developed a microfluidic isothermal amplification detection system.The DNA optimal amplification temperature is obtained;the starting time of exponential amplification of DNA is put forward farther.The optimal condition of DNA amplification in microenvironment,with a little reaction materials and early starting exponential amplification time of DNA are very important for clinic DNA detection and the application of Lab-on-a-Chip.

Advances in micropillar arrays in cellular biomechanics detectionand tissue engineering

Cellular biomechanical features contributed to the occurrence and development of various physiological andpathological phenomena. Micropillar arrays have emerged as an important tool for both the assessment andmanipulation of cellular biomechanical characteristics. This comprehensive review provides an in-depthunderstanding of the fabrication methodologies of micropillar arrays and their applications in deciphering and finetuning cellular biomechanical properties and the innovative experimental platforms including organ-on-a-chip andorganoids-on-a-chip. This review provides novel insights into the potential of micropillar technology, poised toupdate the landscape of stem cell research and tissue engineering.

Endowing a plain fluidic chip with micro-optics: a holographic microscope slide

Lab-on-a-Chip(LoC)devices are extremely promising in that they enable diagnostic functions at the point-of-care.Within this scope,an important goal is to design imaging schemes that can be used out of the laboratory.In this paper,we introduce and test a pocket holographic slide that allows digital holography microscopy to be performed without an interferometer setup.Instead,a commercial off-the-shelf plastic chip is engineered and functionalized with this aim.The microfluidic chip is endowed with micro-optics,that is,a diffraction grating and polymeric lenses,to build an interferometer directly on the chip,avoiding the need for a reference arm and external bulky optical components.Thanks to the single-beam scheme,the system is completely integrated and robust against vibrations,sharing the useful features of any common path interferometer.Hence,it becomes possible to bring holographic functionalities out of the lab,moving complexity from the external optical apparatus to the chip itself.Label-free imaging and quantitative phase contrast mapping of live samples are demonstrated,along with flexible refocusing capabilities.Thus,a liquid volume can be analyzed in one single shot with no need for mechanical scanning systems.

On-chip wireless silicon photonics: from reconfigurable interconnects to lab-on-chip devices

Photonic integrated circuits are developing as key enabling components for high-performance computing and advanced networkon-chip,as well as other emerging technologies such as lab-on-chip sensors,with relevant applications in areas from medicine and biotechnology to aerospace.These demanding applications will require novel features,such as dynamically reconfigurable light pathways,obtained by properly harnessing on-chip optical radiation.In this paper,we introduce a broadband,high directivity(4150),low loss and reconfigurable silicon photonics nanoantenna that fully enables on-chip radiation control.We propose the use of these nanoantennas as versatile building blocks to develop wireless(unguided)silicon photonic devices,which considerably enhance the range of achievable integrated photonic functionalities.As examples of applications,we demonstrate 160 Gbit s−1 data transmission over mm-scale wireless interconnects,a compact low-crosstalk 12-port crossing and electrically reconfigurable pathways via optical beam steering.Moreover,the realization of a flow micro-cytometer for particle characterization demonstrates the smart system integration potential of our approach as lab-on-chip devices.

Characterization of Leaf-Inspired Microfluidic Chips for Pumpless Fluid Transport

Microfluidic networks are extensively used in miniaturized lab-on-a-chip systems. However, most of the existing micro- channels are simply designed and the corresponding microfluidic systems commonly require external pumps to achieve effec- tive fluid transport. Here we employed microfabrication techniques to replicate naturally-optimized leaf venations into synthetic hydrogels for the fabrication of pumpless microfluidic chips. The unique properties of leaf-inspired microfluidic network in convectively transporting fluid were characterized at different inclination angles. Flow velocity inside these microfluidic net- works was quantitatively measured with Particle Image Velocimetry （PIV）. Mass diffusion from biomimetic microfluidic network to surrounding bulk hydrogels was investigated. The results demonstrate that the leaf-inspired microfluidic network can not only effectively transport fluid without the use of external pumps, but also facilitate rapid mass diffusion within bulk hy- drogel chips. These leaf-inspired microfluidic networks could be potentially used to engineer complex pumpless or- gan-on-a-chip systems.

Superior LSPR substrates based on electromagnetic decoupling for on-a-chip high-throughput label-free biosensing

Localized surface plasmon resonance(LSPR)biosensing based on supported metal nanoparticles offers unparalleled possibilities for high-end miniaturization,multiplexing and high-throughput label-free molecular interaction analysis in real time when integrated within an opto-fluidic environment.However,such LSPR-sensing devices typically contain extremely large regions of dielectric materials that are open to molecular adsorption,which must be carefully blocked to avoid compromising the device readings.To address this issue,we made the support essentially invisible to the LSPR by carefully removing the dielectric material overlapping with the localized plasmonic fields through optimized wet-etching.The resulting LSPR substrate,which consists of gold nanodisks centered on narrow SiO2 pillars,exhibits markedly reduced vulnerability to nonspecific substrate adsorption,thus allowing,in an ideal case,the implementation of thicker and more efficient passivation layers.We demonstrate that this approach is effective and fully compatible with state-of-the-art multiplexed real-time biosensing technology and thus represents the ideal substrate design for high-throughput label-free biosensing systems with minimal sample consumption.

Application of microfluidic technologies on COVID-19 diagnosis and drug discovery

The ongoing coronavirus disease 2019(COVID-19) pandemic has boosted the development of antiviral research.Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) diagnosis and drug discovery.In this review,we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design.We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid,antibodies,and antigens.We highlight the contribution of lab-on-a-chip to manufacturing point-ofcare equipment of accurate,sensitive,low-cost,and user-friendly virus-detection devices.We then investigate the efforts in organ-on-a-chip and lipid nanoparticles(LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation.Microfluidic technologies contribute to the ongoing SARSCoV-2 research efforts and provide tools for future viral outbreaks.