Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

All biological processes use or produce heat.Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes.Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters,resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips.Here we present a new,versatile,and robust microcalorimetric differential design based on the integration of heat flux sensors on top of microfluidic channels.We show the design,modeling,calibration,and experimental verification of this system by utilizing Escherichia coli growth and the exothermic base catalyzed hydrolysis of methyl paraben as use cases.The system consists of a Polydimethylsiloxane based flow-through microfluidic chip with two 46µl chambers and two integrated heat flux sensors.The differential compensation of thermal power measurements allows for the measurement of bacterial growth with a limit of detection of 1707 W/m^(3),corresponding to 0.021OD(2·10^(7) bacteria).We also extracted the thermal power of a single Escherichia coli of between 1.3 and 4.5 pW,comparable to values measured by industrial microcalorimeters.Our system opens the possibility for expanding already existing microfluidic systems,such as drug testing lab-on-chip platforms,with measurements of metabolic changes of cell populations in form of heat output,without modifying the analyte and minimal interference with the microfluidic channel itself.

Fluorescence and SEM correlative microscopy for nanomanipulation of subcellular structures

Nanomanipulation under scanning electron microscopy(SEM)enables direct interactions of a tool with a sample.We recently developed a nanomanipulation technique for the extraction and identification of DNA contained within sub-nuclear locations of a single cell nucleus.In nanomanipulation of sub-cellular structures,a key step is to identify targets of interest through correlating fluorescence and SEM images.The DNA extraction task must be conducted with low accelerating voltages resulting in low imaging resolutions.This is imposed by the necessity of preserving the biochemical integrity of the sample.Such poor imaging conditions make the identification of nanometer-sized fiducial marks difficult.This paper presents an affine scale-invariant feature transform(ASIFT)based method for correlating SEM images and fluorescence microscopy images.The performance of the image correlation approach under different noise levels and imaging magnifications was quantitatively evaluated.The optimal mean absolute error(MAE)of correlation results is 68634 nm under standard conditions.Compared with manual correlation by skilled operators,the automated correlation approach demonstrates a speed that is higher by an order of magnitude.With the SEM-fluorescence image correlation approach,targeted DNA was successfully extracted via nanomanipulation under SEM conditions.

Vertical integration of microchips by magnetic assembly and edge wire bonding

The out-of-plane integration of microfabricated planar microchips into functional three-dimensional(3D)devices is a challenge in various emerging MEMS applications such as advanced biosensors and flow sensors.However,no conventional approach currently provides a versatile solution to vertically assemble sensitive or fragile microchips into a separate receiving substrate and to create electrical connections.In this study,we present a method to realize vertical magnetic-field-assisted assembly of discrete silicon microchips into a target receiving substrate and subsequent electrical contacting of the microchips by edge wire bonding,to create interconnections between the receiving substrate and the vertically oriented microchips.Vertical assembly is achieved by combining carefully designed microchip geometries for shape matching and striped patterns of the ferromagnetic material(nickel)on the backside of the microchips,enabling controlled vertical lifting directionality independently of the microchip’s aspect ratio.To form electrical connections between the receiving substrate and a vertically assembled microchip,featuring standard metallic contact electrodes only on its frontside,an edge wire bonding process was developed to realize ball bonds on the top sidewall of the vertically placed microchip.The top sidewall features silicon trenches in correspondence to the frontside electrodes,which induce deformation of the free air balls and result in both mechanical ball bond fixation and around-the-edge metallic connections.The edge wire bonds are realized at room temperature and show minimal contact resistance(<0.2Ω)and excellent mechanical robustness(>168 mN in pull tests).In our approach,the microchips and the receiving substrate are independently manufactured using standard silicon micromachining processes and materials,with a subsequent heterogeneous integration of the components.Thus,this integration technology potentially enables emerging MEMS applications that require 3D out-of-plane assembly of microchips.

Manufacture and characterization of graphene membranes with suspended silicon proof masses for MEMS and NEMS applications

Graphene’s unparalleled strength,chemical stability,ultimate surface-to-volume ratio and excellent electronic properties make it an ideal candidate as a material for membranes in micro-and nanoelectromechanical systems(MEMS and NEMS).However,the integration of graphene into MEMS or NEMS devices and suspended structures such as proof masses on graphene membranes raises several technological challenges,including collapse and rupture of the graphene.We have developed a robust route for realizing membranes made of double-layer CVD graphene and suspending large silicon proof masses on membranes with high yields.We have demonstrated the manufacture of square graphene membranes with side lengths from 7µm to 110µm,and suspended proof masses consisting of solid silicon cubes that are from 5µm×5µm×16.4µm to 100µm×100µm×16.4µm in size.Our approach is compatible with wafer-scale MEMS and semiconductor manufacturing technologies,and the manufacturing yields of the graphene membranes with suspended proof masses were>90%,with>70%of the graphene membranes having>90%graphene area without visible defects.The measured resonance frequencies of the realized structures ranged from tens to hundreds of kHz,with quality factors ranging from 63 to 148.The graphene membranes with suspended proof masses were extremely robust,and were able to withstand indentation forces from an atomic force microscope(AFM)tip of up to~7000nN.The proposed approach for the reliable and large-scale manufacture of graphene membranes with suspended proof masses will enable the development and study of innovative NEMS devices with new functionalities and improved performances.

Integrating MEMS and ICs

The majority of microelectromechanical system(MEMS)devices must be combined with integrated circuits(ICs)for operation in larger electronic systems.While MEMS transducers sense or control physical,optical or chemical quantities,ICs typically provide functionalities related to the signals of these transducers,such as analog-to-digital conversion,amplification,filtering and information processing as well as communication between the MEMS transducer and the outside world.Thus,the vast majority of commercial MEMS products,such as accelerometers,gyroscopes and micro-mirror arrays,are integrated and packaged together with ICs.There are a variety of possible methods of integrating and packaging MEMS and IC components,and the technology of choice strongly depends on the device,the field of application and the commercial requirements.In this review paper,traditional as well as innovative and emerging approaches to MEMS and IC integration are reviewed.These include approaches based on the hybrid integration of multiple chips(multi-chip solutions)as well as system-on-chip solutions based on wafer-level monolithic integration and heterogeneous integration techniques.These are important technological building blocks for the‘More-Than-Moore’paradigm described in the International Technology Roadmap for Semiconductors.In this paper,the various approaches are categorized in a coherent manner,their merits are discussed,and suitable application areas and implementations are critically investigated.The implications of the different MEMS and IC integration approaches for packaging,testing and final system costs are reviewed.

Capillary pumping independent of the liquid surface energy and viscosity

Capillary pumping is an attractive means of liquid actuation because it is a passive mechanism,i.e.,it does not rely on an external energy supply during operation.The capillary flow rate generally depends on the liquid sample viscosity and surface energy.This poses a problem for capillary-driven systems that rely on a predictable flow rate and for which the sample viscosity or surface energy are not precisely known.Here,we introduce the capillary pumping of sample liquids with a flow rate that is constant in time and independent of the sample viscosity and sample surface energy.These features are enabled by a design in which a well-characterized pump liquid is capillarily imbibed into the downstream section of the pump and thereby pulls the unknown sample liquid into the upstream pump section.The downstream pump geometry is designed to exert a Laplace pressure and fluidic resistance that are substantially larger than those exerted by the upstream pump geometry on the sample liquid.Hence,the influence of the unknown sample liquid on the flow rate is negligible.We experimentally tested pumps of the new design with a variety of sample liquids,including water,different samples of whole blood,different samples of urine,isopropanol,mineral oil,and glycerol.The capillary filling speeds of these liquids vary by more than a factor 1000 when imbibed to a standard constant cross-section glass capillary.In our new pump design,20 filling tests involving these liquid samples with vastly different properties resulted in a constant volumetric flow rate in the range of 20.96–24.76μL/min.We expect this novel capillary design to have immediate applications in lab-on-a-chip systems and diagnostic devices.

Micro 3D printing of a functional MEMS accelerometer

Microelectromechanical system(MEMS)devices,such as accelerometers,are widely used across industries,including the automotive,consumer electronics,and medical industries.MEMS are efficiently produced at very high volumes using large-scale semiconductor manufacturing techniques.However,these techniques are not viable for the costefficient manufacturing of specialized MEMS devices at low-and medium-scale volumes.Thus,applications that require custom-designed MEMS devices for markets with low-and medium-scale volumes of below 5000–10,000 components per year are extremely difficult to address efficiently.The 3D printing of MEMS devices could enable the efficient realization and production of MEMS devices at these low-and medium-scale volumes.However,current micro-3D printing technologies have limited capabilities for printing functional MEMS.Herein,we demonstrate a functional 3D-printed MEMS accelerometer using 3D printing by two-photon polymerization in combination with the deposition of a strain gauge transducer by metal evaporation.We characterized the responsivity,resonance frequency,and stability over time of the MEMS accelerometer.Our results demonstrate that the 3D printing of functional MEMS is a viable approach that could enable the efficient realization of a variety of custom-designed MEMS devices,addressing new application areas that are difficult or impossible to address using conventional MEMS manufacturing.

A large-area single-filament infrared emitter and its application in a spectroscopic ethanol gas sensing system

Nondispersive infrared(NDIR)spectroscopy is an important technology for highly accurate and maintenance-free sensing of gases,such as ethanol and carbon dioxide.However,NDIR spectroscopy systems are currently too expensive,e.g.,for consumer and automotive applications,as the infrared(IR)emitter is a critical but costly component of these systems.Here,we report on a low-cost large-area IR emitter featuring a broadband emission spectrum suitable for small NDIR gas spectroscopy systems.The infrared emitter utilizes Joule heating of a Kanthal(FeCrAI)filament that is integrated in the base substrate using an automated high-speed wire bonding process,enabling simple and rapid formation of a long meander-shaped filament.We describe the critical infrared emitter characteristics,including the effective infrared emission spectrum,thermal frequency response,and power consumption.Finally,we integrate the emitter into a handheld breath alcohol analyzer and show its operation in both laboratory and real-world settings,thereby demonstrating the potential of the emitter for future low-cost optical gas sensor applications.

Integrated silicon ohotonic MEMS

Silicon photonics has emerged as a mature technology that is expected to play a key role in critical emerging applications,including very high data rate optical communications,distance sensing for autonomous vehicles,photonic-accelerated computing,and quantum information processing.The success of silicon photonics has been enabled by the unique combination of performance,high yield,and high-volume capacity that can only be achieved by standardizing manufacturing technology.Today,standardized silicon photonics technology platforms implemented by foundries provide access to optimized library components,including low-loss optical routing,fast modulation,continuous tuning,high-speed germanium photodiodes,and high-effciency optical and electrical interfaces.However,silicon's relatively weak electro-optic effects result in modulators with a significant footprint and thermo-optic tuning devices that require high power consumption,which are substantial impediments for very large-scale integration in silicon photonics.Microelectromechanical systems(MEMS)technology can enhance silicon photonics with building blocks that are compact,low-loss,broadband,fast and require very low power consumption.Here,we introduce a silicon photonic MEMS platform consisting of high-performance nano-opto-electromechanical devices fully integrated alongside standard silicon photonics foundry components,with wafer-level sealing for long-term reliability,flip-chip bonding to redistribution interposers,and fibre-array attachment for high port count optical and electrical interfacing.Our experimental demonstration of fundamental silicon photonic MEMS circuit elements,including power couplers,phase shifters and wavelength-division multiplexing devices using standardized technology lifts previous impediments to enable scaling to very large photonic integrated circuits for applications in telecommunications,neuromorphic computing,sensing,programmable photonics,and quantum computing.

Nanoelectromechanical Sensors Based on Suspended 2D Materials

The unique properties and atomic thickness of two-dimensional(2D)materials enable smaller and better nanoelectromechanical sensors with novel functionalities.During the last decade,many studies have successfully shown the feasibility of using suspended membranes of 2D materials in pressure sensors,microphones,accelerometers,and mass and gas sensors.In this review,we explain the different sensing concepts and give an overview of the relevant material properties,fabrication routes,and device operation principles.Finally,we discuss sensor readout and integration methods and provide comparisons against the state of the art to show both the challenges and promises of 2D material-based nanoelectromechanical sensing.

Efficient DNA-assisted synthesis of trans-membrane gold nanowires

Whereas electric circuits and surface-based(bio)chemical sensors are mostly constructed in-plane due to ease of manufacturing,3D microscale and nanoscale structures allow denser integration of electronic components and improved mass transport of the analyte to(bio)chemical sensor surfaces.This work reports the first out-of-plane metallic nanowire formation based on stretching of DNA through a porous membrane.We use rolling circle amplification(RCA)to generate long single-stranded DNA concatemers with one end anchored to the surface.The DNA strands are stretched through the pores in the membrane during liquid removal by forced convection.Because the liquid–air interface movement across the membrane occurs in every pore,DNA stretching across the membrane is highly efficient.The stretched DNA molecules are transformed into trans-membrane gold nanowires through gold nanoparticle hybridization and gold enhancement chemistry.A 50 fM oligonucleotide concentration,a value two orders of magnitude lower than previously reported for flat surface-based nanowire formation,was sufficient for nanowire formation.We observed nanowires in up to 2.7% of the membrane pores,leading to an across-membrane electrical conductivity reduction from open circuit to <20Ω.The simple electrical read-out offers a high signal-to-noise ratio and can also be extended for use as a biosensor due to the high specificity and scope for multiplexing offered by RCA.

Off-stoichiometry improves the photostructuring of thiol-enes through diffusion-induced monomer depletion

Thiol–enes are a group of alternating copolymers with highly ordered networks and are used in a wide range of applications.Here,“click”chemistry photostructuring in off-stoichiometric thiol–enes is shown to induce microscale polymeric compositional gradients due to species diffusion between non-illuminated and illuminated regions,creating two narrow zones with distinct compositions on either side of the photomask feature boundary:a densely cross-linked zone in the illuminated region and a zone with an unpolymerized highly off-stoichiometric monomer composition in the non-illuminated region.Using confocal Raman microscopy,it is here explained how species diffusion causes such intricate compositional gradients in the polymer and how offstoichiometry results in improved image transfer accuracy in thiol–ene photostructuring.Furthermore,increasing the functional group off-stoichiometry and decreasing the photomask feature size is shown to amplify the induced gradients,which potentially leads to a new methodology for microstructuring.

Soft metamaterial with programmable ferromagnetism

Magnetopolymers are of interest in smart material applications;however,changing their magnetic properties post synthesis is complicated.In this study,we introduce easily programmable polymer magnetic composites comprising 2D lattices of droplets of solid-liquid phase change material,with each droplet containing a single magnetic dipole particle.These composites are ferromagnetic with a Curie temperature defined by the rotational freedom of the particles above the droplet melting point.We demonstrate magnetopolymers combining high remanence characteristics with Curie temperatures below the composite degradation temperature.We easily reprogram the material between four states:(1)a superparamagnetic state above the melting point which,in the absence of an external magnetic field,spontaneously collapses to;(2)an artificial spin ice state,which after cooling forms either;(3)a spin glass state with low bulk remanence,or;(4)a ferromagnetic state with high bulk remanence when cooled in the presence of an external magnetic field.We observe the spontaneous emergence of 2D magnetic vortices in the spin ice and elucidate the correlation of these vortex structures with the external bulk remanence.We also demonstrate the easy programming of magnetically latching structures.

Correction to:Efficient DNA-assisted synthesis of trans-membrane gold nanowires

Figure 2 and the descriptive text in the Section“SEM characterization of synthesized nanowires”of the previously published version of this Article were erroneous.The authors would like to replace Fig.2 and section“SEM characterization of synthesized nanowires”with the figure and text below.

Wafer-level hermetically sealed silicon photonic MEMS

The emerging fields of silicon(Si) photonic micro–electromechanical systems(MEMS) and optomechanics enable a wide range of novel high-performance photonic devices with ultra-low power consumption, such as integrated optical MEMS phase shifters, tunable couplers, switches, and optomechanical resonators. In contrast to conventional SiO;-clad Si photonics, photonic MEMS and optomechanics have suspended and movable parts that need to be protected from environmental influence and contamination during operation. Wafer-level hermetic sealing can be a cost-efficient solution, but Si photonic MEMS that are hermetically sealed inside cavities with optical and electrical feedthroughs have not been demonstrated to date, to our knowledge. Here, we demonstrate wafer-level vacuum sealing of Si photonic MEMS inside cavities with ultra-thin caps featuring optical and electrical feedthroughs that connect the photonic MEMS on the inside to optical grating couplers and electrical bond pads on the outside. We used Si photonic MEMS devices built on foundry wafers from the iSiPP50G Si photonics platform of IMEC, Belgium. Vacuum confinement inside the sealed cavities was confirmed by an observed increase of the cutoff frequency of the electro-mechanical response of the encapsulated photonic MEMS phase shifters, due to reduction of air damping. The sealing caps are extremely thin, have a small footprint, and are compatible with subsequent flip-chip bonding onto interposers or printed circuit boards. Thus, our approach for sealing of integrated Si photonic MEMS clears a significant hurdle for their application in high-performance Si photonic circuits.