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.

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.

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.

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.

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.

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.

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.

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.

Chip-scale gas chromatography:From injection through detection

Miniaturized gas chromatography(μGC)systems hold potential for the rapid analysis of volatile organic compounds(VOCs)in an extremely compact and low-power enabled platform.Here,we utilize microfabrication technology to demonstrate the single chip integration of the key components of aμGC system in a two-step planar fabrication process.The 1.5×3 cm microfluidic platform includes a sample injection unit,a micromachined semi-packed separation column(μSC)and a micro-helium discharge photoionization detector(μDPID).The sample injection unit consists of a T-shaped channel operated with an equally simple setup involving a single three-way fluidic valve,a micropump for sample loading and a carrier gas supply for subsequent analysis of the VOCs.The innovative sample injection technique described herein requires a loading time of only a few seconds and produces sharp and repeatable sample pulses(full width at half maximum of approximately 200 ms)at a carrier gas flow rate that is compatible with efficient chromatographic separation.Furthermore,our comprehensive characterization of the chip reveals that a wide variety of VOCs with boiling points in the range of 110–216℃ can be analyzed in less than 1 min by optimizing the flow and temperature programming conditions.Moreover,the analysis of four VOCs at the concentration level of one part per million in an aqueous sample(which corresponds to a headspace concentration in the lower parts-per-billion regime)was performed with a sampling time of only 6 s.The μDPID has demonstrated a linear dynamic range over three orders of magnitude.The system presented here could potentially be used to monitor hazardous VOCs in real time in industrial workplaces and residential settings.

An Optimised Surface Structure for Passive, Unidirectional Fluid Transport Bioinspired by True Bugs

Some true bug species use droplet-shaped,open-capillary structures for passive,unidirectional fluid transport on their body surface in order to spread a defensive fluid to protect themselves against enemies.In this paper we investigated if the shape of the structures found on bugs(bug-structure)could be optimised with regard to better performance in unidirectional fluid transportation.Furthermore,to use this kind of surface structure in technical applications where fluid surface interaction occurs,it is necessary to adapt the structure geometry to the contact angle between fluid and surface.Based on the principal of operation of the droplet-shaped structures,we optimised the structure shape for better performance in targeted fluid flow and increase in flexibility in design of the structure geometry.To adapt the structure geometry and the structure spacing to the contact angle,we implemented an equilibrium simulation of the,the structure surrounding,fluid.In order to verify the functionality of the optimised structure,we designed and manufactured a prototype.By testing this prototype with pure water used as fluid,the functionality of the optimised structure and the simulation could be proved.This kind of structure may be used on technical surfaces where targeted fluid transport is needed,e.g.evacuation of condensate in order to prevent the surface from mold growth,microfluidics,lab-on-a-chip applications and on microneedles for efficient drug/vaccine coating.

自动芯片实验室平台

Agilent公司的5100 Automated Lab-on-a-chip Platform，一个完全自动的电泳工作流操作，每个流程允许无人值守分析多达3，840DNA和蛋白样本。使用样本和试剂的量最小，减少有害废物和每个样本的费用。基于它的自动和内部访问标准，5100Automated Lab-on-a-chip Platform提供重现性的，可比较的数据。