Search

Common buckwheat (Fagopyrum esculentum M.) is an important traditional miscellaneous grain crop. However, seed-shattering is a significant problem in common buckwheat. To investigate the genetic architecture and genetic regulation of seed-shattering in common buckwheat, we constructed a genetic linkage map using the F2 population of Gr (green-flower mutant and shattering resistance) and UD (white flower and susceptible to shattering), which included eight linkage groups with 174 loci, and detected seven QTLs of pedicel strength. RNA-seq analysis of pedicel in two parents revealed 214 differentially expressed genes DEGs that play roles in phenylpropanoid biosynthesis, vitamin B6 metabolism, and flavonoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) was performed and screened out 19 core hub genes. Untargeted GC-MS analysis detected 138 different metabolites and conjoint analysis screened out 11 DEGs, which were significantly associated with differential metabolites. Furthermore, we identified 43 genes in the QTLs, of which six genes had high expression levels in the pedicel of common buckwheat. Finally, 21 candidate genes were screened out based on the above analysis and gene function. Our results provided additional knowledge for the identification and functions of causal candidate genes responsible for the variation in seed-shattering and would be an invaluable resource for the genetic dissection of common buckwheat resistance-shattering molecular breeding.

Background: There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied. Purpose: To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism. Methods: Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway. Results: Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn’t toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway. Conclusion: BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.

High-precision isolation of small extracellular vesicles (sEVs) from biofluids is essential toward developing next-generation liquid biopsies and regenerative therapies. However, current methods of sEV separation require specialized equipment and time-consuming protocols and have difficulties producing highly pure subpopulations of sEVs. Here, we present Acoustic Nanoscale Separation via Wave-pillar Excitation Resonance (ANSWER), which allows single-step, rapid (96% small exosomes, >80% exomeres) fractionation of sEV subpopulations from biofluids without the need for any sample preprocessing. Particles are iteratively deflected in a size-selective manner via an excitation resonance. This previously unidentified phenomenon generates patterns of virtual, tunable, pillar-like acoustic field in a fluid using surface acoustic waves. Highly precise sEV fractionation without the need for sample preprocessing or complex nanofabrication methods has been demonstrated using ANSWER, showing potential as a powerful tool that will enable more in-depth studies into the complexity, heterogeneity, and functionality of sEV subpopulations.

High-molecular-weight polymeric nanoparticles are critical to increasing the loading efficacy and tuning the release profile of targeted molecules for medical diagnosis, imaging, and therapeutics. Although a number of microfluidic approaches have attained reproducible nanoparticle synthesis, it is still challenging to fabricate nanoparticles from high-molecular-weight polymers in a size and structure-controlled manner. In this work, an acoustofluidic platform is developed to synthesize size-tunable, high-molecular-weight (>45 kDa) poly (lactic-co-glycolic acid)-b-poly (ethylene glycol) (PLGA-PEG) nanoparticles without polymer aggregation by exploiting the characteristics of complete and ultrafast mixing. Moreover, the acoustofluidic approach achieves two features that have not been achieved by existing microfluidic approaches: (1) multi-step (≥2) sequential nanoprecipitation in a single device, and (2) synthesis of core-shell structured PLGA-PEG/lipid nanoparticles with high molecular weights. The developed platform expands microfluidic potential in nanomaterial synthesis, where high-molecular-weight polymers, multiple reagents, or sequential nanoprecipitations are needed. An acoustofluidic platform is developed to synthesize high-molecular-weight polymeric nanoparticles in a size- and structure-controlled manner, while eliminating polymer aggregation within the microchannel. S. Zhao, P.H. Huang, H. Zhang, J. Rich, H. Bachman, J. Ye, W. Zhang, C. Chen, Z. Xie, Z. Tian, P. Kang, H. Fu, T. J. Huang

In this research, bismuth and tellurium based thermoelectric materials are studied and electrodeposition method was adapted to fabricate the devices. To improve the thermoelectric performance, the thickness of the patterned films was attempted to be increased up to 30 µm. Film properties, such as morphology, composition, resistivity and thermoelectric output, of p-type Cu-added Bi-Sb-Te films were investigated. It was found that the thermoelectric properties were improved with an increase in the film thickness. An annealed buffer layer was created as substrate to control the morphology of Bi-Sb-Te films to be more compact and denser. Finally, 30 µm thick p-type Bi-Sb-Te patterned-films were successfully fabricated, indicating the applicability to micro-thermoelectric devices.

Acoustic-based techniques can manipulate particles in a label-free, contact-free, and biocompatible manner. However, most previous work in acoustic manipulation has been constrained by axisymmetric patterns of pressure nodes and antinodes. Acoustic holography is an emerging technique that offers the potential to generate arbitrary pressure distributions which can be applied to particle manipulation with higher degrees of freedom. However, since current acoustic holography techniques rely on acoustic radiation forces, which decrease dramatically when the target particle size decreases, they have difficulty manipulating particles in the micro/nanoscale. Here, we introduce a holography technique that leverages both an arbitrary acoustic field and controllable fluid motion to offer an effective approach for manipulating micro/nano particles. Our approach, termed acoustofluidic holography (AFH), can manipulate a variety of materials, including cells, polymers, and metals, across sizes ranging from hundreds of micrometers to tens of nanometers.

Separation of nano/micro particles based on surface acoustic waves (SAWs) has shown great promise for biological, chemical, and medical applications ranging from sample purification to cancer diagnosis. However, the permanent bonding of a microchannel onto relatively expensive piezoelectric substrates and excitation transducers renders the SAW separation devices non-disposable. This limitation not only requires cumbersome cleaning and increased labor and material costs, but also leads to cross-contamination, preventing its implementation in many biological, chemical, and medical applications. Here, we demonstrate a high-performance, disposable acoustofluidic platform for nano/micro particle separation. Leveraging unidirectional interdigital transducers (IDT), a hybrid channel design with hard/soft materials, and the tilted-angle standing SAW (taSSAW), our disposable acoustofluidic devices achieve acoustic radiation forces comparable to those generated by existing permanently bonded, non-disposable devices. Our disposable devices can separate not only microparticles but also nanoparticles. Moreover, it can differentiate bacteria from human red blood cells (RBCs) with a purity of up to 96%. Altogether, we developed a unidirectional IDT-based, disposable acoustofluidic platform for micro/nano particle separation that can achieve high separation efficiency, versatility, and biocompatibility.

Previous efforts to evaluate the detection of human papilloma viral (HPV) DNA in whole saliva as a diagnostic measure for HPV-associated oropharyngeal cancer (HPV-OPC) have not shown sufficient clinical performance. We hypothesize that salivary exosomes are packaged with HPV-associated biomarkers, and efficient enrichment of salivary exosomes through isolation can enhance diagnostic and prognostic performance for HPV-OPC. In this study, an acoustofluidic (the fusion of acoustics and microfluidics) platform was developed to perform size-based isolation of salivary exosomes. These data showed that this platform is capable of consistently isolating exosomes from saliva samples, regardless of viscosity variation and collection method. Compared with the current gold standard, differential centrifugation, droplet digital RT-PCR analysis showed that the average yield of salivary exosomal small RNA from the acoustofluidic platform is 15 times higher. With this high-yield exosome isolation platform, we show that HPV16 DNA could be detected in isolated exosomes from the saliva of HPV-associated OPC patients at 80% concordance with tissues/biopsies positive for HPV16. Overall, these data demonstrated that the acoustofluidic platform can achieve high-purity and high-yield salivary exosome isolation for downstream salivary exosome–based liquid biopsy applications. Additionally, HPV16 DNA sequences in HPV-OPC patients are packaged in salivary exosomes and their isolation will enhance the detection of HPV16 DNA.

In this era of artificial intelligence (AI), the Internet of things (IoT) with the capability of connecting a great number of heterogeneous terminals and the popularity of mobile devices, which makes more devices available as another pair of eyes for people, such as video surveillance and smart navigation. As image enhancement is assisting people to better work together and helping people live a smarter life, it is therefore becoming increasingly important. Nevertheless, many vision systems are sensitive to factors like the scattering of light or motion which may cause blur. This paper promotes an image enhancement method and is dedicated to reduce the adverse effects of blurred images on vision systems. We first researched the theory of indented frame over fusion (IFOF) and presented an automatic screening function. Then subtly combined color reversal, registration and transformation. Lastly, we tested two examples with this method and gained good results. Image processed by this method, facing strong scattering of light environment, has improved its quality and visual effects. With the development of this kind of technology, there will be more practical and intelligent applications in our lives, such as license plate numbers recognition in bad weather and important items search on fire scenes.

Contact-free manipulation of small objects (e.g., cells, tissues, and droplets) using acoustic waves eliminates physical contact with structures and undesired surface adsorption. Pioneering acoustic-based, contact-free manipulation techniques (e.g., acoustic levitation) enable programmable manipulation but are limited by evaporation, bulky transducers, and inefficient acoustic coupling in air. Herein, we report an acoustofluidic mechanism for the contactless manipulation of small objects on water. A hollow-square-shaped interdigital transducer (IDT) is fabricated on lithium niobate (LiNbO(3)), immersed in water and used as a sound source to generate acoustic waves and as a micropump to pump fluid in the ± x and ± y orthogonal directions. As a result, objects which float adjacent to the excited IDT can be pushed unidirectionally (horizontally) in ± x and ± y following the directed acoustic wave propagation. A fluidic processor was developed by patterning IDT units in a 6-by-6 array. We demonstrate contactless, programmable manipulation on water of oil droplets and Zebrafish larvae. This acoustofluidic-based manipulation opens avenues for the contactless, programmable processing of materials and small biosamples.

In this article, we demonstrate an acoustofluidic device for cell lysis using the acoustic streaming effects induced by acoustically oscillating sharp-edged structures. The acoustic streaming locally generates high shear forces that can mechanically rupture cell membranes. With the acoustic-streaming-derived shear forces, our acoustofluidic device can perform cell lysis in a continuous, reagent-free manner, with a lysis efficiency of more than 90% over a range of sample flow rates. We demonstrate that our acoustofluidic lysis device works well on both adherent and non-adherent cells. We also validate it using clinically relevant samples such as red blood cells infected with malarial parasites. Additionally, the unique capability of our acoustofluidic device was demonstrated by performing downstream protein analysis and gene profiling without additional washing steps post-lysis. Our device is simple to fabricate and operate while consuming a relatively low volume of samples. These advantages and other features including the reagent-free nature and controllable lysis efficiency make our platform valuable for many biological and biomedical applications, particularly for the development of point-of-care platforms.

Controllable, precise, and stable rotational manipulation of model organisms is valuable in many biomedical, bioengineering, and biophysics applications. We present an acoustofluidic chip capable of rotating Caenorhabditis elegans (C. elegans) in both static and continuous flow in a controllable manner. Rotational manipulation was achieved by exposing C. elegans to a surface acoustic wave (SAW) field that generated a vortex distribution inside a microchannel. By selectively activating interdigital transducers, we achieved bidirectional rotation of C. elegans, namely counterclockwise and clockwise, with on-demand switching of rotation direction in a single chip. In addition to continuous rotation, we also rotated C. elegans in a step-wise fashion with a step angle as small as 4° by pulsing the signal duration of SAW from a continuous signal to a pulsed signal down to 1.5 ms. Using this device, we have clearly imaged the dopaminergic neurons of C. elegans with pdat-1:GFP expression, as well as the vulval muscles and muscle fibers of the worm with myo-3::GFP fusion protein expression in different orientations and three dimensions. These achievements are difficult to realize through conventional (i.e., non-confocal) microscopy. The SAW manipulations did not detectably affect the health of the model organisms. With its precision, controllability, and simplicity in fabrication and operation, our acoustofluidic devices will be well-suited for model organism studies.

The boom of plant phenotype highlights the need to measure the physiological characteristics of an individual plant. However, continuous real‐time monitoring of a plant's internal physiological status remains challenging using traditional silicon‐based sensor technology, due to the fundamental mismatch between rigid sensors and soft and curved plant surfaces. Here, the first flexible electronic sensing device is reported that can harmlessly cohabitate with the plant and continuously monitor its stem sap flow, a critical plant physiological characteristic for analyzing plant health, water consumption, and nutrient distribution. Due to a special design and the materials chosen, the realized plant‐wearable sensor is thin, soft, lightweight, air/water/light‐permeable, and shows excellent biocompatibility, therefore enabling the sap flow detection in a continuous and non‐destructive manner. The sensor can serve as a noninvasive, high‐throughput, low‐cost toolbox, and holds excellent potentials in phenotyping. Furthermore, the real‐time investigation on stem flow insides watermelon reveals a previously unknown day/night shift pattern of water allocation between fruit and its adjacent branch, which has not been reported before., A plant‐wearable sensor in situ reveals water transport inside a plant. Due to a special design and the materials chosen, the realized plant‐wearable sensor is thin, soft, lightweight, air/water/light‐permeable, and shows excellent biocompatibility, therefore enabling detection in a continuous and non‐destructive manner.

Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae. This enables multispectral imaging of the zebrafish body and internal organs from different viewing perspectives. Moreover, we develop a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation of basic morphological characteristics and advanced combinations of metrics. With its contactless nature and advantages in speed and automation, our acoustofluidic rotational tweezing system has the potential to be a valuable asset in numerous fields, especially for developmental biology, small molecule screening in biochemistry, and pre-clinical drug development in pharmacology., Existing methods of zebrafish phenotyping rely on contact-based processes. Here the authors report on an acoustofluidic-based platform which performs contactless specimen rotation, that results in multispectral images for rapid morphological phenotyping of zebrafish larvae.

The ability to precisely manipulate nano-objects on a large scale can enable the fabrication of materials and devices with tunable optical, electromagnetic, and mechanical properties. However, the dynamic, parallel manipulation of nanoscale colloids and materials remains a significant challenge. Here, we demonstrate acoustoelectronic nanotweezers, which combine the precision and robustness afforded by electronic tweezers with versatility and large-field dynamic control granted by acoustic tweezing techniques, to enable the massively parallel manipulation of sub-100 nm objects with excellent versatility and controllability. Using this approach, we demonstrated the complex patterning of various nanoparticles (e.g., DNAs, exosomes, ~3 nm graphene flakes, ~6 nm quantum dots, ~3.5 nm proteins, and ~1.4 nm dextran), fabricated macroscopic materials with nano-textures, and performed high-resolution, single nanoparticle manipulation. Various nanomanipulation functions, including transportation, concentration, orientation, pattern-overlaying, and sorting, have also been achieved using a simple device configuration. Altogether, acoustoelectronic nanotweezers overcome existing limitations in nano-manipulation and hold great potential for a variety of applications in the fields of electronics, optics, condensed matter physics, metamaterials, and biomedicine., Precise and dynamic manipulation of nano-objects on a large scale has been challenging. Here, the authors introduce acoustoelectronic nanotweezers, combining precision of electronic tweezers with large-field dynamic control of acoustic tweezers, demonstrating complex patterning of sub-100 nm objects.

Effectively isolating and categorizing large quantities of Caenorhabditis elegans (C. elegans) based on different phenotypes is important for most worm research, especially genetics. Here we present an integrated acoustofluidic chip capable of identifying worms of interest based on expression of a fluorescent protein in a continuous flow and then separate them accordingly in a high-throughput manner. Utilizing planar fiber optics as the detection unit, our acoustofluidic device requires no temporary immobilization of worms for interrogation/detection, thereby improving the throughput. Implementing surface acoustic waves (SAW) as the sorting unit, our device provides a contact-free method to move worms of interest to the desired outlet, thus ensuring the biocompatibility for our chip. Our device can sort worms of different developmental stages (L3 and L4 stage worms) at high throughput and accuracy. For example, L3 worms can be processed at a throughput of around 70 worms per min with a sample purity over 99%, which remains over 90% when the throughput is increased to around 115 worms per min. In our acoustofluidic chip, the time period to complete the detection and sorting of one worm is only 50 ms, which outperforms nearly all existing microfluidics-based worm sorting devices and may be further reduced to achieve higher throughput.

Acoustofluidic centrifugation enables the spinning of a fluidic droplet and nanoparticle enrichment and separation., Liquid droplets have been studied for decades and have recently experienced renewed attention as a simplified model for numerous fascinating physical phenomena occurring on size scales from the cell nucleus to stellar black holes. Here, we present an acoustofluidic centrifugation technique that leverages an entanglement of acoustic wave actuation and the spin of a fluidic droplet to enable nanoparticle enrichment and separation. By combining acoustic streaming and droplet spinning, rapid (

Whether reagents and samples need to be combined to achieve a desired reaction, or precise concentrations of solutions need to be mixed and delivered downstream, thorough mixing remains a critical step in many microfluidics-based biological and chemical assays and analyses. To achieve complete mixing of fluids in microfluidic devices, researchers have utilized novel channel designs or active intervention to facilitate mass transport and exchange of fluids. However, many of these solutions have a major limitation: their design inherently limits their operational throughput; that is, different designs work at specific flow rates, whether that be low or high ranges, but have difficulties outside of their tailored design regimes. In this work, we present an acoustofluidic mixer that is capable of achieving efficient, thorough mixing across a broad range of flow rates (20–2000 μL min(−1)) using a single device. Our mixer combines active acoustofluidic mixing, which is responsible for mixing fluids at lower flow rates, with passive hydrodynamic mixing, which accounts for mixing fluids at higher flow rates. The mechanism, functionality, and performance of our acoustofluidic device are both numerically and experimentally validated. Additionally, the real-world potential of our device is demonstrated by synthesizing polymeric nanoparticles with comparable sizes over a two-order-of-magnitude wide range of flow rates. This device can be valuable in many biochemical, biological, and biomedical applications. For example, using our platform, one may synthesize nanoparticles/nanomaterials at lower flow rates to first identify optimal synthesis conditions without having to waste significant amounts of reagents, and then increase the flow rate to perform high-throughput synthesis using the optimal conditions, all using the same single device and maintaining performance.

For decades, scientists have pursued the goal of performing automated reactions in a compact fluid processor with minimal human intervention. Most advanced fluidic handling technologies (e.g., microfluidic chips and micro-well plates) lack fluid rewritability, and the associated benefits of multi-path routing and re-programmability, due to surface-adsorption-induced contamination on contacting structures. This limits their processing speed and the complexity of reaction test matrices. We present a contactless droplet transport and processing technique called digital acoustofluidics which dynamically manipulates droplets with volumes from 1 nL to 100 µL along any planar axis via acoustic-streaming-induced hydrodynamic traps, all in a contamination-free (lower than 10−10% diffusion into the fluorinated carrier oil layer) and biocompatible (99.2% cell viability) manner. Hence, digital acoustofluidics can execute reactions on overlapping, non-contaminated, fluidic paths and can scale to perform massive interaction matrices within a single device., Contamination is an obstacle to the functioning of microfluidic devices. Here the authors exploit acoustic streaming to manipulate droplets which float on a layer of immiscible oil. This prevents contamination and enables rewritability by which different fluids can be used on the same substrate.

Acoustic streaming has been widely used in microfluidics to manipulate various micro-/nano-objects. In this work, acoustic streaming activated by interdigital transducers (IDT) immersed in highly viscous oil is studied numerically and experimentally. In particular, we developed a modeling strategy termed the “slip velocity method” that enables a 3D simulation of surface acoustic wave microfluidics in a large domain (4×4×2 mm(3)) and at a high frequency (23.9 MHz). The experimental and numerical results both show that on top of the oil, all the acoustic streamlines converge at two horizontal stagnation points above the two symmetric sides of the IDT. At these two stagnation points, water droplets floating on the oil can be trapped. Based on these characteristics of the acoustic streaming field, we designed a surface acoustic wave microfluidic device with an integrated IDT array fabricated on a 128°YX LiNbO(3) substrate to perform programmable, contactless droplet manipulation. By activating IDTs accordingly, the water droplets on the oil can be moved to the corresponding traps. With its excellent capability for manipulating droplets in a highly programmable, controllable manner, our surface acoustic wave microfluidic devices are valuable for on-chip contactless sample handling and chemical reactions.

Prostate cancer is one of the most common male malignancies, and MiR-21 plays an important role in the pathogenesis of this cancer. The treatment of microRNAs has proven to be a viable strategy for tumor therapy. However, the delivery of genes remains a major challenge because of the lack of efficient carriers. In this study, a diblock copolymer PEG–PAsp(DETA) of biocompatible polyethylene glycol (PEG) and biodegradable poly(L-aspartic acid) grafted with diethylenetriamine (PAsp(DETA)) was introduced as a delivery vector for an miR-21 inhibitor (i.e. antisense oligonucleotides for miR-21). Using in vitro and in vivo animal experiments, we studied the transfection efficiency and mechanism of action of the PEG–PAsp(DETA)/miR-21 inhibitor towards prostate cancer PC-3 cells. The biodegradable polymer mPEG–PAsp(DETA) was successfully used as a gene carrier to effectively transport the miR-21 inhibitor into PC-3 cells, which resulted in miR-21 silencing, upregulation of PDCD4 gene expression, and induced apoptosis in PC-3 prostate cancer. Meanwhile, the cytotoxicity of biodegradable carriers is very low. This study demonstrates the potential of our novel nucleic acid nanomedicine for the effective treatment of prostate cancer.

The switching of acoustic streaming vortices allows the contactless gating and routing of microliter droplets with scalability., Advances in lab-on-a-chip technologies are driven by the pursuit of programmable microscale bioreactors or fluidic processors that mimic electronic functionality, scalability, and convenience. However, few fluidic mechanisms allow for basic logic operations on rewritable fluidic paths due to cross-contamination, which leads to random interference between “fluidic bits” or droplets. Here, we introduce a mechanism that allows for contact-free gating of individual droplets based on the scalable features of acoustic streaming vortices (ASVs). By shifting the hydrodynamic equilibrium positions inside interconnected ASVs with multitonal electrical signals, different functions such as controlling the routing and gating of droplets on rewritable fluidic paths are demonstrated with minimal biochemical cross-contamination. Electrical control of this ASV-based mechanism allows for unidirectional routing and active gating behaviors, which can potentially be scaled to functional fluidic processors that can regulate the flow of droplets in a manner similar to the current in transistor arrays.

Synthesis of nanoparticles and particulate nanomaterials with tailored properties is a central step toward many applications ranging from energy conversion and imaging/display to biosensing and nanomedicine. While existing microfluidics‐based synthesis methods offer precise control over the synthesis process, most of them rely on passive, partial mixing of reagents, which limits their applicability and potentially, adversely alter the properties of synthesized products. Here, an acoustofluidic (i.e., the fusion of acoustic and microfluidics) synthesis platform is reported to synthesize nanoparticles and nanomaterials in a controllable, reproducible manner through acoustic‐streaming‐based active mixing of reagents. The acoustofluidic strategy allows for the dynamic control of the reaction conditions simply by adjusting the strength of the acoustic streaming. With this platform, the synthesis of versatile nanoparticles/nanomaterials is demonstrated including the synthesis of polymeric nanoparticles, chitosan nanoparticles, organic–inorganic hybrid nanomaterials, metal–organic framework biocomposites, and lipid‐DNA complexes. The acoustofluidic synthesis platform, when incorporated with varying flow rates, compositions, or concentrations of reagents, will lend itself unprecedented flexibility in establishing various reaction conditions and thus enable the synthesis of versatile nanoparticles and nanomaterials with prescribed properties.

Previous efforts to evaluate the detection of human papilloma viral (HPV) DNA in whole saliva as a diagnostic measure for HPV-associated oropharyngeal cancer (HPV-OPC) have not shown sufficient clinical performance. We hypothesize that salivary exosomes are packaged with HPV-associated biomarkers, and efficient enrichment of salivary exosomes through isolation can enhance diagnostic and prognostic performance for HPV-OPC. In this study, an acoustofluidic (the fusion of acoustics and microfluidics) platform was developed to perform size-based isolation of salivary exosomes. These data showed that this platform is capable of consistently isolating exosomes from saliva samples, regardless of viscosity variation and collection method. Compared with the current gold standard, differential centrifugation, droplet digital RT-PCR analysis showed that the average yield of salivary exosomal small RNA from the acoustofluidic platform is 15 times higher. With this high-yield exosome isolation platform, we show that HPV16 DNA could be detected in isolated exosomes from the saliva of HPV-associated OPC patients at 80% concordance with tissues/biopsies positive for HPV16. Overall, these data demonstrated that the acoustofluidic platform can achieve high-purity and high-yield salivary exosome isolation for downstream salivary exosome–based liquid biopsy applications. Additionally, HPV16 DNA sequences in HPV-OPC patients are packaged in salivary exosomes and their isolation will enhance the detection of HPV16 DNA.