Heterogeneous Integration of Acoustic Microextraction with an Optoelectronic Sensor on Glass for Nucleic Acid Testing.

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.

Microfluidic confined acoustic streaming vortex for liposome synthesis.

Liposomes have garnered significant attention owing to their favorable characteristics as promising carriers. Microfluidic based hydrodynamic flow focusing, or micro-mixing approaches enable precise control of liposome size during their synthesis due to the comparable size scale. However, current microfluidic approaches still have issues such as high flow rate dependency, complex chip structures, and ease of clogging. Herein, we present a novel microfluidic platform for size-tunable liposome synthesis based on an ultra-high-frequency acoustic resonator. By designing the shape and orientation of the acoustic resonator in the three-phase laminar flow, it combined the features of both hydrodynamic flow focusing and rapid micro-mixing. The distribution of lipid precursor solution in laminar flow and the mixing conditions could be regulated by the confined acoustic streaming vortex. We successfully synthesize liposomes with adjustable sizes and narrow size distributions. Notably, this platform regulates the product size by adjusting only the input power, which is less dependent on the flow rate. Furthermore, the vortex-like fluid flow generated along the device edge effectively prevents precipitation due to excessive lipid concentration or contact with the wall.

Rapid purification and enrichment of viral particles using self-propelled micromotors.

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.

On-Chip Monolithic Integrated Multimode Carbon Nanotube Sensor for a Gas Chromatography Detector.

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.

A portable nucleic acid extraction system based on gigahertz acoustic tweezers.

In this study, a portable and compatible system for extraction of DNA based on gigahertz acoustic was proposed and verified. The system is based on tunable multiple acoustic tweezers which can switch between the mixing and separation mode to enable the efficient DNA extraction with a relatively small and portable setup. Using this system, we extracted DNA from the rat's whole blood and achieved about 80% recovery. By combining with real-time qPCR, this proposed detection method was able to detect adenovirus (ADV) DNA as low as 102 IU/mL.Clinical Relevance-The whole system is only in centimeter scale and can be applied for portable DNA extraction. There is great potential application in molecular diagnostics and point of care test (POCT).

A novel design for passive misscromixers based on topology optimization method.

In this paper, a series of novel passive micromixers, called topological micromixers with reversed flow (TMRFX), are proposed. The reversed flow in the microchannels can enhance chaotic advection and produce better mixing performance. Therefore the maximum of reversed flow is chosen as the objective function of the topology optimization problem. Because the square-wave unit is easier to fabricate and have better mixing performance than many other serpentine micromixers, square-wave structure becomes the original geometry structure. By simulating analysis, the series of TMRFX, namely TMRF, TMRF0.75, TMRF0.5, TMRF0.25, mix better than the square-wave micromixer at various Reynolds numbers (Re), but pressure drops of TMRFX are much higher. Lots of intensive numerical simulations are conducted to prove that TMRF and TMRF0.75 have remarkable advantages on mixing over other micromixers at various Re. The mixing performance of TMRF0.75 is similar to TMRF's. What's more, TMRF have a larger pressure drop than TMRF0.75, which means that TMRF have taken more energy than TMRF0.75. For a wide range of Re (Re ≤ 0.1 and Re ≥ 10), TMRF0.75 delivers a great performance and the mixing efficiency is greater than 95 %. Even in the range of 0.1-10 for the Re, the mixing efficiency of TMRF0.75 is higher than 85 %.

PMMA microreactor for chemiluminescence detection of Cu (II) based on 1,10-Phenanthroline-hydrogen peroxide reaction.

A microreactor for the chemiluminescence detection of copper (II) in water samples, based on the measurement of light emitted from the copper (II) catalysed oxidation of 1,10-phenanthroline by hydrogen peroxide in basic aqueous solution, is presented. Polymethyl methacrylate (PMMA) was chose as material for fabricating the microreactor with mill and hot bonding method. Optimized reagents conditions were found to be 6.3 × 10(-5)mol/L 1,10-phenanthroline, 1.5 × 10(-3)mol/L hydrogen peroxide, 7.0 × 10(-2)mol/L sodium hydroxide and 2.4 × 10(-5)mol/L Hexadecyl trimethyl ammonium Bromide (CTMAB). In the continuous flow injection mode the system can perform fully automated detection with a reagent consumption of only 3.5 µL each time. The linear range of the Cu (II) ions concentration was 1.5 × 10(-8) mol/L to 1.0 × 10(-4) mol/L, and the detection limit was 9.4 × 10(-9)mol/L with the S/N ratio of 4. The relative standard deviation was 3.0 % for 2.0 × 10(-6) mol/L Cu (II) ions (n = 10). The most obvious features of the detection method are simplicity, rapidity and easy fabrication of the microreactor.