Microfluidic-based nucleic acid testing (NAT) has been proven as an alternative approach for in-situ and rapid NA detection. However, these on-chip methods still require complex peripherals, which contradict the purpose of point-of-care (POC) applications. One of the major challenges is the integration of NA purification and amplification in a miniaturized setup with high mass and heat transfer efficiency. Here, we propose a hand-held in-situ nucleic acid detection device featuring a dual-functional GHz acoustofluidic resonator. The device is designed to utilize GHz acoustic streaming and acoustothermal effects to address both liquid mixing and heating issues, ensuring uniform reaction conditions and consistent thermal management in the microfluidic channel. By replacing traditional magnetic beads with polystyrene beads as matrix for solid-phase microextraction, the redundant washing and elution steps are eliminated, thereby simplifying the NA extraction process. The mixing and heating functions can be seamlessly switched by adjusting the applied power, thereby enhancing NA processing without the need for additional peripherals. The developed hand-held NAT apparatus achieved a detection limit of 10³ copies per milliliter in complex plasma samples within 35 min. Our method simplifies workflows, improves NA retention, and is suitable for processing complex biological samples, making it ideal for POC and in-field testing applications.
Supramolecules are considered as promising materials for volatile organic compounds (VOCs) sensing applications. The proper understanding of the sorption process taking place in host-guest interactions is critical in improving the pattern recognition of supramolecules-based sensing arrays. Here, we report a novel approach to investigate the dynamic host-guest recognition process by employing a bulk acoustic wave (BAW) resonator capable of producing multiple oscillation amplitudes and simultaneously recording multiple responses to VOCs. Self-assembled monolayers (SAMs) of β-cyclodextrin (β-CD) were modified on four BAW sensors to demonstrate the gas-surface interactions regarding oscillation amplitude and SAM length. Based on the method, a virtual sensor array (VSA) type electronic nose (e-nose) can be realized by pattern recognition of multiple responses at different oscillation amplitudes of a single sensor. VOCs analysis was realized respectively by using principal component analysis (PCA) for individual VOC identification and linear discriminant analysis (LDA) for VOCs mixtures classification.
Multiplexed flow cytometry, known for its powerful high-throughput identification capability, is widely applied across various biomedical and clinical fields. However, classical flow cytometry relies on multichannel lasers and detectors, which are significant in cost and size, limiting their application in miniaturized assays. Herein, we developed an acoustic streaming-based flow cytometry technique that focuses on multisized microbeads flowing sheathlessly. This method enables the discrimination of particle types and the quantification of target protein concentrations using only a single detector. Microbeads of different sizes exhibit distinct behaviors in the continuous acoustic streaming tunnel, leading to an increased velocity difference during their transition under the laser spot. Consequently, a size detection method based on "velocity stretching" has been established. A multiplex assay of three proteins: cardiac troponin I, creatine kinase-MB and myoglobin, in acute myocardial infarction is performed to validate the feasibility and evaluate the performance of the system. This new multiplexed flow cytometry strategy is expected to enable low-cost and onsite detection of multiple biomarkers.
Lab-on-a-chip systems (LOCs), characterized by their high sensitivity, low sample consumption, and portability, have significantly advanced the field of on-site testing. Despite the evolution of integrated LOCs from qualitative to quantitative analyses, on-chip full integration of sample preparation, purification, and multiplexed detection remains a challenge. Here, we propose a strategy for the heterogeneous integration of a set of complementary metal oxide semiconductor-compatible devices including acoustic resonator, thin-film resistors, and temperature/photosensors as a new type of LOC for nucleic acid testing (NAT). Programmed acoustic streaming-based particles and fluid manipulations largely simplify the nucleic acid extraction process including cell lysis, nucleic acid capture, and elution. The design of the acoustic microextraction module and extraction process was thoroughly studied. Benefitted by the microelectromechanical system approach, the conventional mechanical actions and complex flow control are avoided, which enables a compact hand-held NAT instrument without complicated peripherals. Validation experiments conducted on plasma-harboring mutations in the epidermal growth factor receptor (EGFR) gene confirmed the robustness of the system, achieving an impressive nucleic acid (NA) extraction efficiency of approximately 90% within 5 min and a limit of detection of the target NA in the plasma of 1 copy/μL.
Micro gas chromatography (& mu;GC) using microfabricated silicon columns has been developed in response to the requirement for portable on-site gas analysis. Although different stationary phases have been de-veloped, repeatable and reliable surface coatings in these rather small microcolumns remains a challenge. Herein, a new stationary phase coating strategy using magnetic beads (MBs) as carriers for micro col-umn is presented. MBs modified with organopolysiloxane (MBs@OV-1) and a metal organic framework (MBs@HKUST-1) are deposited in on-chip microcolumns assisted with a magnetic field with an opti-mized modification process. MBs@OV-1 column showed a minimum HETP of 0.074 cm (1351 plates/m) of 62 cm/s. Mixtures of volatile organic compounds are successfully separated using MBs carried stationary phase which demonstrates that this technique has good chromatographic column efficiency. This method not only provides a novel coating process, washing and characterization of the stationary phases but also establishes a straightforward strategy for testing new absorbent materials for & mu;GC systems.& COPY; 2023 Elsevier B.V. All rights reserved.
Small-sized, high-sensitivity, and low-cost sensors are required for gas-sensing applications because of their critical role in environmental monitoring, clinic diagnosis, process control, and anti-terrorism. Given the rapid developments in micro-fabrication and microelectromechanical system (MEMS) technologies, film bulk acoustic resonator (FBAR) gas sensors have received increased research attention because of their improved working frequency and reliability. This chapter discusses the state-of-the-art and recent developments in FBAR gas sensors. The sensing mechanism and limitations of these sensors are summarized. Recent progress in the development of four major aspects of FBAR gas sensors, namely, FBAR gas sensors using different sensing materials, FBAR gas sensors used in electronic noses, system integration of FBAR gas sensors, and FBAR gas sensors used as micro-GC detectors, is reviewed. The potential future of FBAR sensors used in flexible electronics is also discussed.
Viral particles bind to receptors through multivalent protein interactions. Such high avidity interactions on sensor surfaces are less studied. In this work, three polyelectrolytes that can form biosensing surfaces with different interfacial characteristics in probe density and spatial arrangement were designed. Quartz crystal microbalance, interferometry and atomic force microscopy were used to study their surface density and binding behaviors with proteins and virus particles. A multivalent adsorption kinetic model was developed to estimate the number of bonds from the viral particles bound to the polyelectrolyte surfaces. Experimental results show that the heterogeneous 3D surface with jagged forest-like structure enhances the virus capture ability by maximizing the multivalent interactions. As a proof of concept, specific coronavirus detection was achieved in spiked swab samples. These results indicate the importance of both probe density and their spatial arrangement on the sensing performance, which could be used as a guideline for rational biosensing surface design.
Nanochannel-based resistive pulse sensing (nano-RPS) system is widely used for the high-sensitive measurement and characterization of nanoscale biological particles and biomolecules due to its high surface to volume ratio. However, the geometric dimensions and surface properties of nanochannel are usually fixed, which limit the detections within particular ranges or types of nanoparticles. In order to improve the flexibility of nano-RPS system, it is of great significance to develop nanochannels with tunable dimensions and surface properties. In this work, we proposed a novel multi-module self-assembly (MS) strategy which allows to shrink the geometric dimensions and tune surface properties of the nanochannels simultaneously. The MS-tuned nano-RPS device exhibits an enhanced signal-to-noise ratio (SNR) for nanoparticle detections after shrunk the geometric dimensions by MS strategy. Meanwhile, by tuning the surface charge, an enhanced resolution for viral particles detection was achieved with the MS-tuned nano-RPS devices by analyzing the variation of pulse width due the tuned surface charge. The proposed MS strategy is versatile for various types of surface materials and can be potentially applied for nanoscale surface reconfiguration in various nanofluidic devices.
Virus infections remain one of the principal causes of morbidity and mortality worldwide. The current gold standard approach for diagnosing pathogens requires access to reverse transcription-polymerase chain reaction (RT-PCR) technology. However, separation and enrichment of the targets from complex and diluted samples remains a major challenge. In this work, we proposed a micromotor-based sample preparation concept for the efficient separation and concentration of target viral particles before PCR. The micromotors are functionalized with antibodies with a 3D polymer linker and are capable of self-propulsion by the catalytic generation of oxygen bubbles for selective and positive virus enrichment. This strategy significantly improves the enrichment efficiency and recovery rate of virus (up to 80% at 104 tu mL-1 in a 1 mL volume within just 6 min) without external mixing equipment. The method allows the Ct value in regular PCR tests to appear 6-7 cycles earlier and a detection limit of 1 tu mL-1 for the target virus from swap samples. A point-of-need test kit is designed based on the micromotors which can be readily applied to pretreat a large volume of samples.
This work demonstrates a gas flow rate sensor based on the curvature change of a micro quartz resonator (MQR). We explored the relationship between the resonant frequency shift and gas flow rate theoretically and experimentally. The sensing performance was evaluated by exposing the device to nitrogen gas at different flow rates. Experimental results indicate that the response time is less than 2 s with a sensitivity of 0.16 Hz/(mL·min −l ) in the gas flow ranging from 100 to 800 mL/min. Compared to the conventional gas sensors, our method has many advantages including low temperature drift, rapid response time, and great reproducibility, and provides a multifunctional sensing platform to measure the concentration and flow rate successfully. To the best of our knowledge, this is the first paper about gas flow rate sensing using the mechanical bending effect of an MQR.
With the rapid spread and multigeneration variation of coronavirus, rapid drug development has become imperative. A major obstacle to addressing this issue is adequately constructing the cell membrane at the molecular level, which enables in vitro observation of the cell response to virus and drug molecules quantitatively, shortening the drug experiment cycle. Herein, we propose a rapid and label-free supported lipid bilayer-based lab-on-a-chip biosensor for the screening of effective inhibition drugs. An extended gate electrode was prepared and functionalized by an angiotensin-converting enzyme II (ACE2) receptor-incorporated supported lipid bilayer (SLB). Such an integrated system can convert the interactions of targets and membrane receptors into real-time charge signals. The platform can simulate the cell membrane microenvironment in vitro and accurately capture the interaction signal between the target and the cell membrane with minimized interference, thus observing the drug action pathway quantitatively and realizing drug screening effectively. Due to these label-free, low-cost, convenient, and integrated advantages, it is a suitable candidate method for the rapid drug screening for the early treatment and prevention of worldwide spread of coronavirus.
Carbon nanotube (CNT)-based chemiresistors are promising gas detectors for gas chromatography (GC) due to their intrinsic nanoscale porosity and excellent electrical conductivity. However, fabrication reproducibility, long desorption time, limited sensitivity, and low dynamic range limit their usage in real applications. This paper reports a novel on-chip monolithic integrated multimode CNT sensor, where a micro-electro-mechanical system-based bulk acoustic wave (BAW) resonator is embedded underneath a CNT chemiresistor. The device fabrication repeatability was improved by on-site monitoring of CNT deposition using BAW. We found that the acoustic stimulation can accelerate the gas desorption rate from the CNT surface, which solves the slow desorption issue. Due to the different sensing mechanisms, the multimode CNT sensor provides complementary responses to targets with improved sensitivity and dynamic range compared to a single mode detector. A prototype of a chromatographic system using the multimode CNT sensor was prepared by dedicated design of the connection between the device and the separation column. Such a GC system is used for the quantitative identification of a gas mixture at different GC conditions, which proves the feasibility of the multimode CNT detector for chromatographic analysis. The as-developed CMOS compatible multimode CNT sensor offers high sensing performance, miniaturized size, and low power consumption, which are critical for developing portable GC.
The application of metal and metal-oxide nanowires in functional electronic nanodevices requires the precise control of the composition and surface alignment of the nanowires. Herein, a facile route for fabricating highly ordered Pt, In2O3, and Pt/In2O3 hybrid nanowire arrays from their acid/salt precursors by nanoscale solution printing is reported. The resulting nanowire arrays are continuous and periodic with sub-100 nm dimensions and aligned in parallel on a silicon substrate. With the prepared metal/metal-oxide nanowire arrays, two types of hydrogen sensors were fabricated. The sensors fabricated with the hybrid Pt/In2O3 nanowire array show better H-2 detection performance than the sensors fabricated with the pure Pt nanowire array with regard to the response amplitude (50 times higher) and the detection limit of the sensor. The improvement of the Pt/In2O3-based sensor compared to the Pt-based sensor indicates the occurrence of an additional enhancing mechanism through the chemical sensitization of the Pt/In2O3-based sensors. Moreover, the sensors were integrated into a compact hydrogen detection system with remote hydrogen (H-2) monitoring and gas leakage warning functions. As the developed approach can be adapted for different materials by simply adjusting the ratio of precursor solutions, it offers a promising straightforward method to fabricate composition-tunable hybrid nanowire arrays for low-cost, scalable, and high-quality nanoscale sensors.
Self-contained microfluidic platforms with on-chip integration of flow control units, microreactors, (bio)sensors, etc. are ideal systems for point-of-care (POC) testing. However, current approaches such as micropumps and microvalves, increase the cost and the control system, and it is rather difficult to integrate into a single chip. Herein, we demonstrated a versatile acoustofluidic platform actuated by a Lamb wave resonator (LWR) array, in which pumping, mixing, fluidic switching, and particle trapping are all achieved on a single chip. The high-speed microscale acoustic streaming triggered by the LWR in the confined microchannel can be utilized to realize a flow resistor and switch. Variable unidirectional pumping was realized by regulating the relative position of the LWR in various custom-designed microfluidic structures and adoption of different geometric parameters for the microchannel. In addition, to realize quantitative biomarker detection, the on-chip flow resistor, micropump, micromixer and particle trapper were also integrated with a CMOS photo sensor and electronic driver circuit, resulting in an automated handheld microfluidic system with no moving parts. Finally, the acoustofluidic platform was tested for prostate-specific antigen (PSA) sensing, which demonstrates the biocompatibility and applied potency of this proposed self-contained system in POC biomedical applications.
Gas separation and detection technology is closely related to people's daily production and life. With the emergence of various detection equipment, it has made remarkable progress in recent decades. Gas sensing materials play an important role in the process of gas separation and detection. Compared with traditional gas sensing materials, metal-organic frameworks (MOFs), as a new type of porous materials, has ultra-large surface area, extremely high porosity, regular pore structure and adjustable pore size. These unique advantages make MOFs particularly suitable as promising candidates for the gas pre-concentration, pre-separation and detection, so as to realize the collection and enhancement of low concentration gas, the separation of complex gas mixtures, and the reliable detection of trace target gases. The detection ability and separation efficiency are greatly improved eventually. Therefore, MOFs are expected to surpass the traditional materials, and their application in gas separation and detection deserves the attention of both academia and industry.
The presence of chemical warfare agents (CWAs) in the environment is a serious threat to human safety, but there are many problems with the currently available detection methods for CWAs. For example, gas chromatography–mass spectrometry cannot be used for in-field detection owing to the rather large size of the equipment required, while commercial sensors have the disadvantages of low sensitivity and poor selectivity. Here, we develop a portable gas sensing instrument for CWA detection that consists of a MEMS-fabricated micro-preconcentrator (μPC) and a film bulk acoustic resonator (FBAR) gas sensor. The μPC is coated with a nanoporous metal–organic framework material to enrich the target, while the FBAR provides rapid detection without the need for extra carrier gas. Dimethyl methylphosphonate (DMMP), a simulant of the chemical warfare agent sarin, is used to test the performance of the instrument. Experimental results show that the μPC provides effective sample pretreatment, while the FBAR gas sensor has good sensitivity to DMMP vapor. The combination of μPC and FBAR in one instrument gives full play to their respective advantages, reducing the limit of detection of the analyte. Moreover, both the μPC and the FBAR are fabricated using a CMOS-compatible approach, and the prototype instrument is compact in size with high portability and thus has potential for application to in-field detection of CWAs.
Smartphone-enabled microfluidic chemiluminescence immunoassay is a promising portable system for point-of-care (POC) biosensing applications. However, due to the rather faint emitted light in such a limited sample volume, it is still difficult to reach the clinically accepted range when the smartphone serves as a standalone detector. Besides, the multiple separation and washing steps during sample preparation hinder the immunoassay's applications for POC usage. Herein, we proposed a novel acoustic streaming tweezers-enabled microfluidic immunoassay, where the probe particles' purification, reaction, and sensing were simply achieved on the same chip at continuous-flow conditions. The dedicatedly designed high-speed microscale vortexes not only enable dynamic trapping and washing of the probe particles on-demand but also enhance the capture efficiency of the heterogeneous particle-based immunoassay through active mixing during trapping. The enriched probe particles and enhanced biomarker capture capability increase the local chemiluminescent light intensity and enable direct capture of the immunobinding signal by a regular smartphone camera. The system was tested for prostate-specific antigen (PSA) sensing both in buffer and serum, where a limit of detection of 0.2 ng/mL and a large dynamic response range from 0.3 to 10 ng/mL using only 10 μL of sample were achieved in a total assay time of less than 15 min. With the advantages of on-chip integration of sample preparation and detection and high sensing performance, the developed POC platform could be applied for many on-site diagnosis applications.
Ambient suspended particulate matter (PM) (primarily with particle diameter 2.5 µm or less, i.e., PM2.5) can adversely affect ecosystems and human health. Currently, optical particle sensors based on light scattering dominate the portable PM sensing market. However, the light scattering method has poor adaptability to different-sized PM and adverse environmental conditions. Here, we design and develop a portable PM sensing microsystem that consists of a micromachined virtual impactor (VI) for particle separation, a thermophoretic deposition chip for particle collection, and an extended-gate field-effect transistor (FET) for particle analysis. This system can realize on-site separation, collection, and analysis of aerosol particles without being influenced by environmental factors. In this study, the design of the VI is thoroughly analyzed by numerical simulation, and mixtures of different-sized silicon dioxide (SiO2) particles are used in an experimental verification of the performance of the VI and FET. Considering the low cost and compact design of the whole system, the proposed PM analysis microsystem has potential for PM detection under a wide range of conditions, such as heavily polluted industrial environments and for point-of-need outdoor and indoor air quality monitoring.
In this paper, we developed a dual-transduction gas sensor by monitoring the changes of resistance and mass to detect benzene, toluene, and xylene (BTX). This gas sensor consists of a solid mounted film bulk acoustic resonator (SMR) with interdigitated electrodes (IDEs) on the resonant area. Multi-walled carbon nanotubes (MWCNTs) were sprayed onto the IDEs by Inkjet Printing methods to serve as the sensitive materials for both the resonator and chemiresistor. While the resonator is a gravimetric sensor and responsive to the added mass, the chemiresistor is an electronic sensor and responsive to the changes in resistance. Therefore, the interaction of MWCNTs to benzene, toluene, and xylene (BTX) can be measured not only by the shift of resonant frequency but also by the change of resistance. This dual-transduction mechanism shows potentials to improve the linear range and detection scopes in gas sensing.