Conformal electronic devices on freeform surface play a critical role in the emerging smart robotics, smart skins, and integrated sensing systems. However, their functional structures such as circuits tend to tear-off, break, or crack under mechanical or thermal influence when in service, thus limiting the application reliability of conformal electronics. Herein, inspired by the tree root system, template-confined additive (TCA) printing technology was presented for reliable fabrication of robust circuits. TCA printing technology involves the penetration of adhesive into the functional material, thereby enhancing the mechanical robustness of the circuits, allowing them to maintain their electrical performance despite the presence of external damaging factors such as scratching, abrasion, folding, and high temperatures. For example, herein, the circuits could withstand mechanical abrasion at temperatures as high as 350 °C without compromising electrical properties. Benefiting from the confines of template, the printed circuits achieved resolutions of up to 300 nm, suitable for various materials such as P(VDF-TrFE), MWCNTs, and AgNPs, which enabled the multi-material self-aligned fabrication. Furthermore, the versatility of TCA printing was presented by fabricating circuits on arbitrary substrates, and realizing various devices, such as conformal temperature/humidity sensing system and epidermal ultra-thin energy storage system. These applications present the significant potential of TCA printing in fabricating intelligent devices.
{"title":"Root-inspired, template-confined additive printing for fabricating high-robust conformal electronics.","authors":"Guifang Liu, Xiangming Li, Yangfan Qiu, Chuanhang Zeng, Xinkai Zhu, Chao Wang, Xiaoliang Chen, Chunhui Wang, Hongmiao Tian, Jinyou Shao","doi":"10.1038/s41378-024-00840-z","DOIUrl":"10.1038/s41378-024-00840-z","url":null,"abstract":"<p><p>Conformal electronic devices on freeform surface play a critical role in the emerging smart robotics, smart skins, and integrated sensing systems. However, their functional structures such as circuits tend to tear-off, break, or crack under mechanical or thermal influence when in service, thus limiting the application reliability of conformal electronics. Herein, inspired by the tree root system, template-confined additive (TCA) printing technology was presented for reliable fabrication of robust circuits. TCA printing technology involves the penetration of adhesive into the functional material, thereby enhancing the mechanical robustness of the circuits, allowing them to maintain their electrical performance despite the presence of external damaging factors such as scratching, abrasion, folding, and high temperatures. For example, herein, the circuits could withstand mechanical abrasion at temperatures as high as 350 °C without compromising electrical properties. Benefiting from the confines of template, the printed circuits achieved resolutions of up to 300 nm, suitable for various materials such as P(VDF-TrFE), MWCNTs, and AgNPs, which enabled the multi-material self-aligned fabrication. Furthermore, the versatility of TCA printing was presented by fabricating circuits on arbitrary substrates, and realizing various devices, such as conformal temperature/humidity sensing system and epidermal ultra-thin energy storage system. These applications present the significant potential of TCA printing in fabricating intelligent devices.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"191"},"PeriodicalIF":7.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-14DOI: 10.1038/s41378-024-00829-8
Yuna Jung, Daniel Gulick, Jennifer Blain Christen
Hydrocephalus is characterized by the accumulation of excess cerebrospinal fluid (CSF) in the cranium due to an imbalance between production and absorption of CSF. The standard treatment involves the implantation of a shunt to divert excess CSF into the peritoneal cavity, but these shunts exhibit high failure rates over time. In pursuit of improved reliability and performance, this study proposes a miniaturized valve designed to mimic the natural one-way valve function of the arachnoid granulations and thereby replace the shunts. A benchtop testing setup was employed to characterize the behavior of the fabricated valve. Additionally, an animal study was conducted to assess the valve's in vivo performance. This involved the injection of saline into the lateral ventricle to elevate intracranial pressure (ICP), followed by the drainage of the saline through the valve inserted into the cisterna magna (CM) to reduce pressure. Our prototype features a silicone duckbill valve design combined with a silicone tube as an inlet. Through benchtop testing, the valve exhibited unidirectional flow with negligible reverse leakage, revealing that critical parameters such as the width of the fluid channel (W) and bill length (L) could be controlled to optimize valve performance. Notably, the valve configuration with W= 0.8mm and L < 0.5mm achieved the lowest cracking pressure (2.22 ± 0.07 mmHg) and outflow resistance (22.00 ± 0.70 mmHg/mL/min) within the low cracking pressure range of conventional shunts. Our observations of the in vivo test demonstrated that when untreated states, pressure differences from baseline to peak exceeded 20 mmHg due to the absence of drainage, resulting in sustained pressure elevation. Conversely, upon treating states by removing the clamp, pressure differences from baseline to peak remained below 5 mmHg, indicating effective drainage of injected saline through the valve. These promising results highlight the potential of the miniaturized duckbill valve as an alternative for ICP management in hydrocephalus, offering improved control and reliability compared to conventional shunting systems. Further research is required to evaluate the valve's performance as a chronic implant.
{"title":"Fabrication and in vivo testing of a sub-mm duckbill valve for hydrocephalus treatment.","authors":"Yuna Jung, Daniel Gulick, Jennifer Blain Christen","doi":"10.1038/s41378-024-00829-8","DOIUrl":"10.1038/s41378-024-00829-8","url":null,"abstract":"<p><p>Hydrocephalus is characterized by the accumulation of excess cerebrospinal fluid (CSF) in the cranium due to an imbalance between production and absorption of CSF. The standard treatment involves the implantation of a shunt to divert excess CSF into the peritoneal cavity, but these shunts exhibit high failure rates over time. In pursuit of improved reliability and performance, this study proposes a miniaturized valve designed to mimic the natural one-way valve function of the arachnoid granulations and thereby replace the shunts. A benchtop testing setup was employed to characterize the behavior of the fabricated valve. Additionally, an animal study was conducted to assess the valve's in vivo performance. This involved the injection of saline into the lateral ventricle to elevate intracranial pressure (ICP), followed by the drainage of the saline through the valve inserted into the cisterna magna (CM) to reduce pressure. Our prototype features a silicone duckbill valve design combined with a silicone tube as an inlet. Through benchtop testing, the valve exhibited unidirectional flow with negligible reverse leakage, revealing that critical parameters such as the width of the fluid channel (W) and bill length (L) could be controlled to optimize valve performance. Notably, the valve configuration with W= 0.8mm and L < 0.5mm achieved the lowest cracking pressure (2.22 ± 0.07 mmHg) and outflow resistance (22.00 ± 0.70 mmHg/mL/min) within the low cracking pressure range of conventional shunts. Our observations of the in vivo test demonstrated that when untreated states, pressure differences from baseline to peak exceeded 20 mmHg due to the absence of drainage, resulting in sustained pressure elevation. Conversely, upon treating states by removing the clamp, pressure differences from baseline to peak remained below 5 mmHg, indicating effective drainage of injected saline through the valve. These promising results highlight the potential of the miniaturized duckbill valve as an alternative for ICP management in hydrocephalus, offering improved control and reliability compared to conventional shunting systems. Further research is required to evaluate the valve's performance as a chronic implant.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"190"},"PeriodicalIF":7.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1038/s41378-024-00824-z
Neng-Zhi Yao, Bin Wang, Hao Wang, Chen-Long Wu, Tien-Mo Shih, Xuesheng Wang
The possibility of freely manipulating flow in accordance with humans will remain indispensable for breakthroughs in fields such as microfluidics, nanoengineering, and biomedicines, as well as for realizing zero-drag hydrodynamics, which is essential for alleviating the global energy crisis. However, persistent challenges arise from the D'Alembert paradox and the unresolved Navier-Stokes solutions, known as the Millennium Problem. These obstacles also complicate the development of hydrodynamic zero-drag cloaks across diverse Reynolds numbers. Our research introduces a paradigm for such cloaks, relying exclusively on isotropic and homogeneous viscosity. Through experimental and numerical validations, our cloaks exhibit zero-drag properties, effectively resolving the D'Alembert paradox in viscous potential flows. Moreover, they possess the capability to activate or deactivate hydrodynamic concealment at will. Our analysis emphasizes the critical role of vorticity manipulation in realizing cloaking effects and drag-reduction technology. Therefore, controlling vorticity emerges as a pivotal aspect for future active hydrodynamic zero-drag cloak designs. In conclusion, our study challenges the prevailing belief in the impossibility of zero drag, offering valuable insights into invisibility characteristics in fluid mechanics with implications for microfluidics, biofluidics demanding the drug release or biomolecules transportation accurately and timely, and hypervelocity technologies.
{"title":"On-demand zero-drag hydrodynamic cloaks resolve D'Alembert paradox in viscous potential flows.","authors":"Neng-Zhi Yao, Bin Wang, Hao Wang, Chen-Long Wu, Tien-Mo Shih, Xuesheng Wang","doi":"10.1038/s41378-024-00824-z","DOIUrl":"10.1038/s41378-024-00824-z","url":null,"abstract":"<p><p>The possibility of freely manipulating flow in accordance with humans will remain indispensable for breakthroughs in fields such as microfluidics, nanoengineering, and biomedicines, as well as for realizing zero-drag hydrodynamics, which is essential for alleviating the global energy crisis. However, persistent challenges arise from the D'Alembert paradox and the unresolved Navier-Stokes solutions, known as the Millennium Problem. These obstacles also complicate the development of hydrodynamic zero-drag cloaks across diverse Reynolds numbers. Our research introduces a paradigm for such cloaks, relying exclusively on isotropic and homogeneous viscosity. Through experimental and numerical validations, our cloaks exhibit zero-drag properties, effectively resolving the D'Alembert paradox in viscous potential flows. Moreover, they possess the capability to activate or deactivate hydrodynamic concealment at will. Our analysis emphasizes the critical role of vorticity manipulation in realizing cloaking effects and drag-reduction technology. Therefore, controlling vorticity emerges as a pivotal aspect for future active hydrodynamic zero-drag cloak designs. In conclusion, our study challenges the prevailing belief in the impossibility of zero drag, offering valuable insights into invisibility characteristics in fluid mechanics with implications for microfluidics, biofluidics demanding the drug release or biomolecules transportation accurately and timely, and hypervelocity technologies.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"188"},"PeriodicalIF":7.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1038/s41378-024-00836-9
Yang Gao, Anwar Elhadad, Seokheun Choi
We introduce a groundbreaking proof-of-concept for a novel glucose monitoring transducing mechanism, marking the first demonstration of a spore-forming microbial whole-cell sensing platform. The approach uses selective and sensitive germination of Bacillus subtilis spores in response to glucose in potassium-rich bodily fluids such as sweat. As the rate of germination and the number of metabolically active germinating cells are directly proportional to glucose concentration, the electrogenic activity of these cells-manifested as electricity-serves as a self-powered transducing signal for glucose detection. Within a microengineered, paper-based microbial fuel cell (MFC), these electrical power outputs are measurable and can be visually displayed through a compact interface, providing real-time alerts. The dormant spores extend shelf-life, and the self-replicating bacteria ensure robustness. The MFC demonstrated a remarkable sensitivity of 2.246 µW·(log mM)-1·cm-2 to glucose concentrations ranging from 0.2 to 10 mM, with a notably lower limit of detection at ~0.07 mM. The sensor exhibited exceptional selectivity, accurately detecting glucose even in the presence of various interferents. Comparative analyses revealed that, unlike conventional enzymatic biosensors whose performance degrades significantly through time even when inactive, the spore-based MFC is stable for extended periods and promptly regains functionality when needed. This preliminary investigation indicates that the spore-forming microbial whole-cell sensing strategy holds considerable promise for efficient diabetes management and can be extended toward noninvasive wearable monitoring, overcoming critical challenges of current technologies and paving the way for advanced biosensing applications.
{"title":"Revolutionary self-powered transducing mechanism for long-lasting and stable glucose monitoring: achieving selective and sensitive bacterial endospore germination in microengineered paper-based platforms.","authors":"Yang Gao, Anwar Elhadad, Seokheun Choi","doi":"10.1038/s41378-024-00836-9","DOIUrl":"10.1038/s41378-024-00836-9","url":null,"abstract":"<p><p>We introduce a groundbreaking proof-of-concept for a novel glucose monitoring transducing mechanism, marking the first demonstration of a spore-forming microbial whole-cell sensing platform. The approach uses selective and sensitive germination of Bacillus subtilis spores in response to glucose in potassium-rich bodily fluids such as sweat. As the rate of germination and the number of metabolically active germinating cells are directly proportional to glucose concentration, the electrogenic activity of these cells-manifested as electricity-serves as a self-powered transducing signal for glucose detection. Within a microengineered, paper-based microbial fuel cell (MFC), these electrical power outputs are measurable and can be visually displayed through a compact interface, providing real-time alerts. The dormant spores extend shelf-life, and the self-replicating bacteria ensure robustness. The MFC demonstrated a remarkable sensitivity of 2.246 µW·(log mM)<sup>-1</sup>·cm<sup>-2</sup> to glucose concentrations ranging from 0.2 to 10 mM, with a notably lower limit of detection at ~0.07 mM. The sensor exhibited exceptional selectivity, accurately detecting glucose even in the presence of various interferents. Comparative analyses revealed that, unlike conventional enzymatic biosensors whose performance degrades significantly through time even when inactive, the spore-based MFC is stable for extended periods and promptly regains functionality when needed. This preliminary investigation indicates that the spore-forming microbial whole-cell sensing strategy holds considerable promise for efficient diabetes management and can be extended toward noninvasive wearable monitoring, overcoming critical challenges of current technologies and paving the way for advanced biosensing applications.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"187"},"PeriodicalIF":7.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-11DOI: 10.1038/s41378-024-00843-w
Gihyun Lee, Soo Jee Kim, Yejin Choi, Jongho Park, Je-Kyun Park
Microextrusion printing is widely used to precisely manufacture microdevices, microphysiological systems, and biological constructs that feature micropatterns and microstructures consisting of various materials. This method is particularly useful for creating biological models that recapitulate in vivo-like cellular microenvironments. Although there is a recent demand for high-throughput data from a single in vitro system, it remains challenging to fabricate multiple models with a small volume of bioinks in a stable and precise manner due to the spreading and evaporation issues of the extruded hydrogel. As printing time increases, the extruded bioink spreads and evaporates, leading to technical problems that decrease printing resolution and stability, as well as biological problems that affect 3D culture space and cell viability. In this study, we describe a novel microextrusion bioprinting technique to stably fabricate a multi-composition array consisting of massive and nanoliter-scale hydrogel dots by using multi-bioink printing and aerosol-based crosslinking techniques to prevent spreading and evaporation issues. We confirmed that the crosslinking aerosol effectively prevented spreading and evaporation by analyzing the morphological changes of the extruded hydrogel. By adjusting the extruding ratio of the bioinks, we were able to print a multi-composition array. This stable and massive array printing technique allowed us to improve the replicates of biological models and provide various data from a single culture system. The array printing technique was applied to recapitulate the intra-tumor heterogeneity of glioblastoma and assess temozolomide efficacy on the array model.
{"title":"Bioprinting of a multi-composition array to mimic intra-tumor heterogeneity of glioblastoma for drug evaluation.","authors":"Gihyun Lee, Soo Jee Kim, Yejin Choi, Jongho Park, Je-Kyun Park","doi":"10.1038/s41378-024-00843-w","DOIUrl":"10.1038/s41378-024-00843-w","url":null,"abstract":"<p><p>Microextrusion printing is widely used to precisely manufacture microdevices, microphysiological systems, and biological constructs that feature micropatterns and microstructures consisting of various materials. This method is particularly useful for creating biological models that recapitulate in vivo-like cellular microenvironments. Although there is a recent demand for high-throughput data from a single in vitro system, it remains challenging to fabricate multiple models with a small volume of bioinks in a stable and precise manner due to the spreading and evaporation issues of the extruded hydrogel. As printing time increases, the extruded bioink spreads and evaporates, leading to technical problems that decrease printing resolution and stability, as well as biological problems that affect 3D culture space and cell viability. In this study, we describe a novel microextrusion bioprinting technique to stably fabricate a multi-composition array consisting of massive and nanoliter-scale hydrogel dots by using multi-bioink printing and aerosol-based crosslinking techniques to prevent spreading and evaporation issues. We confirmed that the crosslinking aerosol effectively prevented spreading and evaporation by analyzing the morphological changes of the extruded hydrogel. By adjusting the extruding ratio of the bioinks, we were able to print a multi-composition array. This stable and massive array printing technique allowed us to improve the replicates of biological models and provide various data from a single culture system. The array printing technique was applied to recapitulate the intra-tumor heterogeneity of glioblastoma and assess temozolomide efficacy on the array model.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"186"},"PeriodicalIF":7.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-10DOI: 10.1038/s41378-024-00800-7
Jufeng Deng, Chong Liu, Marc Madou
Carbon nanofibers show the advantages of scale effects on electrical and mechanical properties for applications such as aerospace1,2, automotive3,4, and energy5,6, but have to confront the challenge of maximizing the role of scale effects. Here, a method of additive nanostructuring and carbonization of polyacrylonitrile (PAN) jetting for the nano-forming of carbon fibers is developed by understanding the electrostatic submicro-initiation of a PAN jetting, altering the microstructure of PAN-based jetting fibers at the nanoscale and implementing subsequent carbonization of PAN jetting nanofiber. Using this method of additive nanostructuring and carbonization in combination with the radial distribution pattern of shear stress, we find that the conformation of some molecular chains inside the PAN nanofibers is transformed into the zigzag conformation. The ability to materialize and carbonize such PAN nanofibers with various conformational structures in the form of arrays on diverse micro-structures and macro-substrates enables the forming of continuous carbon nanofibers with a diameter of ~20 nm and allows the tensile strength of carbon fibers to be enhanced to 212 GPa through the combination of zigzag conformation and nanoscale effects. These advantages create opportunities for the application of maximizing nanoscale effects that have not previously been technically possible.
{"title":"Continuously superior-strong carbon nanofibers by additive nanostructuring and carbonization of polyacrylonitrile jetting.","authors":"Jufeng Deng, Chong Liu, Marc Madou","doi":"10.1038/s41378-024-00800-7","DOIUrl":"10.1038/s41378-024-00800-7","url":null,"abstract":"<p><p>Carbon nanofibers show the advantages of scale effects on electrical and mechanical properties for applications such as aerospace<sup>1,2</sup>, automotive<sup>3,4</sup>, and energy<sup>5,6</sup>, but have to confront the challenge of maximizing the role of scale effects. Here, a method of additive nanostructuring and carbonization of polyacrylonitrile (PAN) jetting for the nano-forming of carbon fibers is developed by understanding the electrostatic submicro-initiation of a PAN jetting, altering the microstructure of PAN-based jetting fibers at the nanoscale and implementing subsequent carbonization of PAN jetting nanofiber. Using this method of additive nanostructuring and carbonization in combination with the radial distribution pattern of shear stress, we find that the conformation of some molecular chains inside the PAN nanofibers is transformed into the zigzag conformation. The ability to materialize and carbonize such PAN nanofibers with various conformational structures in the form of arrays on diverse micro-structures and macro-substrates enables the forming of continuous carbon nanofibers with a diameter of ~20 nm and allows the tensile strength of carbon fibers to be enhanced to 212 GPa through the combination of zigzag conformation and nanoscale effects. These advantages create opportunities for the application of maximizing nanoscale effects that have not previously been technically possible.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"185"},"PeriodicalIF":7.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1038/s41378-024-00815-0
Mostafa Bakouei, Ali Kalantarifard, Indraja Sundara Raju, Tatiana Avsievich, Lauri Rannaste, Marjut Kreivi, Caglar Elbuken
The exceptional ability of liposomes to mimic a cellular lipid membrane makes them invaluable tools in biomembrane studies and bottom-up synthetic biology. Microfluidics provides a promising toolkit for creating giant liposomes in a controlled manner. Nevertheless, challenges associated with the microfluidic formation of double emulsions, as precursors to giant liposomes, limit the full exploration of this potential. In this study, we propose a PDMS-glass capillary hybrid device as a facile and versatile tool for the formation of double emulsions which not only eliminates the need for selective surface treatment, a well-known problem with PDMS formation chips, but also provides fabrication simplicity and reusability compared to the glass-capillary formation chips. These advantages make the presented device a versatile tool for forming double emulsions with varying sizes (spanning two orders of magnitude in diameter), shell thickness, number of compartments, and choice of solvents. We achieved robust thin shell double emulsion formation by operating the hybrid chip in double dripping mode without performing hydrophilic/phobic treatment a priori. In addition, as an alternative to the conventional, time-consuming density-based separation method, a tandem separation chip is developed to deliver double emulsions free of any oil droplet contamination in a continuous and rapid manner without any need for operator handling. The applicability of the device was demonstrated by forming giant liposomes using the solvent extraction method. This easy-to-replicate, flexible, and reliable microfluidic platform for the formation and separation of double emulsion templates paves the way for the high-throughput microfluidic generation of giant liposomes and synthetic cells, opening exciting avenues for biomimetic research. The presented giant liposome assembly line features a novel treatment-free hybrid chip for double emulsion formation coupled with a high throughput separation chip for sample purification.
{"title":"Facile and versatile PDMS-glass capillary double emulsion formation device coupled with rapid purification toward microfluidic giant liposome generation.","authors":"Mostafa Bakouei, Ali Kalantarifard, Indraja Sundara Raju, Tatiana Avsievich, Lauri Rannaste, Marjut Kreivi, Caglar Elbuken","doi":"10.1038/s41378-024-00815-0","DOIUrl":"10.1038/s41378-024-00815-0","url":null,"abstract":"<p><p>The exceptional ability of liposomes to mimic a cellular lipid membrane makes them invaluable tools in biomembrane studies and bottom-up synthetic biology. Microfluidics provides a promising toolkit for creating giant liposomes in a controlled manner. Nevertheless, challenges associated with the microfluidic formation of double emulsions, as precursors to giant liposomes, limit the full exploration of this potential. In this study, we propose a PDMS-glass capillary hybrid device as a facile and versatile tool for the formation of double emulsions which not only eliminates the need for selective surface treatment, a well-known problem with PDMS formation chips, but also provides fabrication simplicity and reusability compared to the glass-capillary formation chips. These advantages make the presented device a versatile tool for forming double emulsions with varying sizes (spanning two orders of magnitude in diameter), shell thickness, number of compartments, and choice of solvents. We achieved robust thin shell double emulsion formation by operating the hybrid chip in double dripping mode without performing hydrophilic/phobic treatment a priori. In addition, as an alternative to the conventional, time-consuming density-based separation method, a tandem separation chip is developed to deliver double emulsions free of any oil droplet contamination in a continuous and rapid manner without any need for operator handling. The applicability of the device was demonstrated by forming giant liposomes using the solvent extraction method. This easy-to-replicate, flexible, and reliable microfluidic platform for the formation and separation of double emulsion templates paves the way for the high-throughput microfluidic generation of giant liposomes and synthetic cells, opening exciting avenues for biomimetic research. The presented giant liposome assembly line features a novel treatment-free hybrid chip for double emulsion formation coupled with a high throughput separation chip for sample purification.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"183"},"PeriodicalIF":7.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1038/s41378-024-00808-z
Wangyang Zhang, Chaoshan Zhao, Haoliang Jia, Tao Liu, Jiaqian Yang, Pengfan Wu, Xiaojing Mu
Ultrasonic biochemical detection is important for biomarker detection, drug monitoring, and medical diagnosis, as it can predict disease progression and enable effective measures to be taken in a timely manner. However, the ultrasonic technology currently used for biochemical marker detection is directly modified on the surface of the device. The associated test methods are costly and unreliable while having poor repeatability; therefore, they cannot achieve low-cost rapid testing. In this study, a detection mechanism based on the Rayleigh scattering of acoustic waves caused by nanoparticles, which causes changes in the received sound pressure, was developed for the first time. The modification of antibodies on an insertable substrate decouples the functionalization step from the sensor surface and facilitates the application of capacitive micromachined ultrasonic transducers (CMUTs) in conjunction with Au nanoparticles (AuNPs) for CA19-9 cancer antigen detection. A corresponding detection theory was established, and the relevant parameters of the theoretical formula were verified using different nanoparticles. Using our fabricated CMUT chip with a resonant frequency of 1 MHz, the concentrations and substances of the CA19-9 antigen markers were successfully measured. In the concentration range of 0.1-1000 U/mL, the receiving voltage decreased with increasing concentration. Further investigations revealed that the influence of other interfering markers in the human body can be ignored, demonstrating the feasibility and robustness of biochemical detection based on CMUTs combined with nanoparticles.
{"title":"Biomarker detection based on nanoparticle-induced ultrasonic Rayleigh scattering.","authors":"Wangyang Zhang, Chaoshan Zhao, Haoliang Jia, Tao Liu, Jiaqian Yang, Pengfan Wu, Xiaojing Mu","doi":"10.1038/s41378-024-00808-z","DOIUrl":"10.1038/s41378-024-00808-z","url":null,"abstract":"<p><p>Ultrasonic biochemical detection is important for biomarker detection, drug monitoring, and medical diagnosis, as it can predict disease progression and enable effective measures to be taken in a timely manner. However, the ultrasonic technology currently used for biochemical marker detection is directly modified on the surface of the device. The associated test methods are costly and unreliable while having poor repeatability; therefore, they cannot achieve low-cost rapid testing. In this study, a detection mechanism based on the Rayleigh scattering of acoustic waves caused by nanoparticles, which causes changes in the received sound pressure, was developed for the first time. The modification of antibodies on an insertable substrate decouples the functionalization step from the sensor surface and facilitates the application of capacitive micromachined ultrasonic transducers (CMUTs) in conjunction with Au nanoparticles (AuNPs) for CA19-9 cancer antigen detection. A corresponding detection theory was established, and the relevant parameters of the theoretical formula were verified using different nanoparticles. Using our fabricated CMUT chip with a resonant frequency of 1 MHz, the concentrations and substances of the CA19-9 antigen markers were successfully measured. In the concentration range of 0.1-1000 U/mL, the receiving voltage decreased with increasing concentration. Further investigations revealed that the influence of other interfering markers in the human body can be ignored, demonstrating the feasibility and robustness of biochemical detection based on CMUTs combined with nanoparticles.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"182"},"PeriodicalIF":7.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1038/s41378-024-00817-y
Shivani Shukla, Joshua L Schwartz, Callum Walsh, Wen Mai Wong, Vrund Patel, Yu-Peng Hsieh, Chichi Onwuasoanya, Shaoming Chen, Andreas Offenhäusser, Gert Cauwenberghs, Francesca Santoro, Alysson R Muotri, Gene W Yeo, Sreekanth H Chalasani, Zeinab Jahed
The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron's action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.
{"title":"Supra- and sub-threshold intracellular-like recording of 2D and 3D neuronal networks using nanopillar electrode arrays.","authors":"Shivani Shukla, Joshua L Schwartz, Callum Walsh, Wen Mai Wong, Vrund Patel, Yu-Peng Hsieh, Chichi Onwuasoanya, Shaoming Chen, Andreas Offenhäusser, Gert Cauwenberghs, Francesca Santoro, Alysson R Muotri, Gene W Yeo, Sreekanth H Chalasani, Zeinab Jahed","doi":"10.1038/s41378-024-00817-y","DOIUrl":"10.1038/s41378-024-00817-y","url":null,"abstract":"<p><p>The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron's action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"184"},"PeriodicalIF":7.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-29DOI: 10.1038/s41378-024-00822-1
George Adedokun, Gurjit Sidhu, Morteza Alipanah, Gary P Wang, Z Hugh Fan
Early and accurate diagnosis of human immunodeficiency virus (HIV) infection is essential for timely initiation of antiretroviral therapy (ART) and prevention of new infections. However, conventional nucleic-acid-based tests for HIV detection require sophisticated laboratory equipment and trained personnel, which are often unavailable at the point-of-care (POC) or unaffordable in resource-limited settings. We report our development of a low-cost, integrated platform for POC testing of HIV. The platform integrates viral nucleic acid extraction on a paper substrate and reverse transcription loop-mediated isothermal amplification (RT-LAMP) in a portable, battery-powered heating device with real-time detection. The platform does not require laboratory infrastructure such as power outlets. The assay showed a detection limit of 30 copies/mL of HIV RNA in 140 μL human serum or 4 copies/reaction using 50 μL human serum, with no cross-reactivity with hepatitis C virus (HCV). We validated the platform using both plasma samples spiked with HIV and clinical samples from HIV-positive individuals, and compared it with standard laboratory assays based on polymerase chain reaction (PCR). These results demonstrate the feasibility of our platform for HIV testing at the POC.
{"title":"A handheld HIV detection platform using paper-based sample preparation and real-time isothermal amplification.","authors":"George Adedokun, Gurjit Sidhu, Morteza Alipanah, Gary P Wang, Z Hugh Fan","doi":"10.1038/s41378-024-00822-1","DOIUrl":"10.1038/s41378-024-00822-1","url":null,"abstract":"<p><p>Early and accurate diagnosis of human immunodeficiency virus (HIV) infection is essential for timely initiation of antiretroviral therapy (ART) and prevention of new infections. However, conventional nucleic-acid-based tests for HIV detection require sophisticated laboratory equipment and trained personnel, which are often unavailable at the point-of-care (POC) or unaffordable in resource-limited settings. We report our development of a low-cost, integrated platform for POC testing of HIV. The platform integrates viral nucleic acid extraction on a paper substrate and reverse transcription loop-mediated isothermal amplification (RT-LAMP) in a portable, battery-powered heating device with real-time detection. The platform does not require laboratory infrastructure such as power outlets. The assay showed a detection limit of 30 copies/mL of HIV RNA in 140 μL human serum or 4 copies/reaction using 50 μL human serum, with no cross-reactivity with hepatitis C virus (HCV). We validated the platform using both plasma samples spiked with HIV and clinical samples from HIV-positive individuals, and compared it with standard laboratory assays based on polymerase chain reaction (PCR). These results demonstrate the feasibility of our platform for HIV testing at the POC.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"10 1","pages":"181"},"PeriodicalIF":7.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}