499 research outputs found
Hybrid Microfluidic Devices For On-Demand Manipulation and Screening of Neurons and Organs of Small Model Organisms
Caenorhabditis elegans and Drosophila melanogaster are widely used model organisms for neurological and cardiac studies due to their simple neuronal and cardiac systems, genome similarity to humans, and ease of maintenance in laboratories. However, their 50m-1mm sizes and continuous mobility impede their precise spatiotemporal manipulation, thereby, reducing the throughput of biological assays. By integrating glass capillaries into microfluidic devices and using 3D-printed fixtures for precise control, we have developed hybrid lab-on-a-chip devices to facilitate the processes of animal manipulation and stimuli control, using modules for single-organism selection, orientation, imaging and chemical stimulation. These microdevices enabled us to manipulate organisms individually and to orient them at any desired direction for imaging purposes. The applications of these hybrid microdevices were demonstrated in the optical and fluorescent imaging of C. elegans cells as well as cardiac screening of Drosophila larvae. This technique can be applied in fundamental biology, toxicology, and drug discovery
Microfluidic technologies for accelerating the clinical translation of nanoparticles
Using nanoparticles for therapy and imaging holds tremendous promise for the treatment of major diseases such as cancer. However, their translation into the clinic has been slow because it remains difficult to produce nanoparticles that are consistent 'batch-to-batch', and in sufficient quantities for clinical research. Moreover, platforms for rapid screening of nanoparticles are still lacking. Recent microfluidic technologies can tackle some of these issues, and offer a way to accelerate the clinical translation of nanoparticles. In this Progress Article, we highlight the advances in microfluidic systems that can synthesize libraries of nanoparticles in a well-controlled, reproducible and high-throughput manner. We also discuss the use of microfluidics for rapidly evaluating nanoparticles in vitro under microenvironments that mimic the in vivo conditions. Furthermore, we highlight some systems that can manipulate small organisms, which could be used for evaluating the in vivo toxicity of nanoparticles or for drug screening. We conclude with a critical assessment of the near- and long-term impact of microfluidics in the field of nanomedicine.Prostate Cancer Foundation (Award in Nanotherapeutics)MIT-Harvard Center for Cancer Nanotechnology Excellence (U54-CA151884)National Heart, Lung, and Blood Institute (Programs of Excellence in Nanotechnology (HHSN268201000045C))National Science Foundation (U.S.) (Graduate Research Fellowship
Small
Screening functional phenotypes in small animals is important for genetics and drug discovery. Multiphase microfluidics has great potential for enhancing throughput but has been hampered by inefficient animal encapsulation and limited control over the animal's environment in droplets. Here, a highly efficient single-animal encapsulation unit, a liquid exchanger system for controlling the droplet chemical environment dynamically, and an automation scheme for the programming and robust execution of complex protocols are demonstrated. By careful use of interfacial forces, the liquid exchanger unit allows for adding and removing chemicals from a droplet and, therefore, generating chemical gradients inaccessible in previous multiphase systems. Using Caenorhabditis elegans as an example, it is demonstrated that these advances can serve to analyze dynamic phenotyping, such as behavior and neuronal activity, perform forward genetic screen, and are scalable to manipulate animals of different sizes. This platform paves the way for large-scale screens of complex dynamic phenotypes in small animals.P40 OD010440/CD/ODCDC CDC HHSUnited States/P40 OD010440/OD/NIH HHSUnited States/R01 AG056436/AG/NIA NIH HHSUnited States/R01NS096581/National Institute of Health/R01AG056436/National Institute of Health/ECCS-1542174/National Science Foundation/National Nanotechnology Coordinated Infrastructure/R01 NS096581/NS/NINDS NIH HHSUnited States/NIH R21NS117066/National Institute of Health/R21 NS117066/NS/NINDS NIH HHSUnited States
Recommended from our members
Microfluidic devices for the rapid and automated processing of sample populations
Microfluidic devices for the rapid and automated processing of sample populations are provided. Described are multiplexer microfluidic devices configured to serially deliver a plurality of distinct sample populations to a sample processing element rapidly and automatically, without cross-contaminating the distinct sample populations. Also provided are microfluidic sample processing elements that can be used to rapidly and automatically manipulate and/or interrogate members of a sample population. The microfluidic devices can be used to improve the throughput and quality of experiments involving model organisms, such as C. elegans.Board of Regents, University of Texas Syste
Micro-electro-opto-fluidic systems for biomedical drug screening and electromagnetic filtering and cloaking applications
Microfluidic is a multidisciplinary field that deals with the flow of liquid inside micro-meter size channels. In order to be considered as microfluidics, at least one dimension of the channel should be in the range of one micrometer or sub-millimeter. Microfluidic technology includes designing, manufacturing, formulating devices and processing the liquid. As numerous bio-science and engineering techniques have utilized microfluidics and highly integrated with this remarkable technology, the microfluidic platform technology has extended to several sub-techs: micro-scale analysis, soft-lithography fabrication, polymer science and processing, on-chip sensing and micro-scale fluid manipulation. Those sub-techs have been developed rapidly along with the booming microfluidics.
The advance of those techniques has promoted microfluidic system diverse and widespread applications. Some examples that employ this technology include on-chip drug screening, micro-scale analysis, flexible electronics, biochemical assays. Many engineering field, such as optics, electronics, chemicals and electromagnetics, have been integrated with the microfluidic system to form a completed system for sensing, analyzing or realizing some specific applications.
Through the fusion of those technologies with microfluidics, many emerging technologies are well initiated, such as optofluidics and electrofluidics. Despite of rapid advancement of each parent technology field, those intersected technologies are still in their infancy and many technological elements and even some fundamental concepts are just now being developed. Thus, it provides great opportunity to explore more about those emerging technologies. Some particular areas that mainly interest researchers including cost deduction, effective fabrication, highly integration, portability and applicability. Due to the wide and diversity nature of the microfluidic technology and numerous combinations from the integration with other fields, it is very difficult to choose a single aspect or particular subject to research. Hence, we would like to focus on the application orientated microfluidic techniques that integrated with other engineering areas, in particular optics and electronics. Correspondingly, I will present four microfluidic platforms that integrated with optics, electronics for different application purpose.
First of all, fiber-optics was integrated into a microfluidic device to detect muscular force generation of microscopic nematodes. The integrated opto-fluidic device is capable of measuring the muscular force of nematode worms normal to the translational movement direction with high sensitivity, high data reliability, and simple device structure. The ability to quantify the muscular forces of small nematode worms will provide a new approach for screening mutants at single animal resolution.
Secondly, electronic grids were integrated into a microfluidic chip to realize on-chip tracking of nematode locomotion. The micro-electro-fluidic approach is capable of real-time lens-less and image-sensor-less monitoring of the locomotion of microscopic nematodes. The technology showed promise for overcoming the constraint of the limited field of view of conventional optical microscopy, with relatively low cost, good spatial resolution, and high portability.
Thirdly, electromagnetic spit ring resonator (SRR) structure was adopted as microfluidic channel filled with liquid metal to fabricate a tunable microfluidic microwave electronics called meta-atom. The presented meta-atom is capable of tuning its electromagnetic (EM) response characteristics over a broad frequency range via simple mechanical stretching. The meta-atom in this study presents a simple but effective building block for realizing mechanically tunable metamaterials.
Finally, based on the meta-atom we previously developed, an array of electromagnetic SRR shaped microfluidic channels filled with liquid metal to form a flexible metamaterial-based microwave electronic “skin” or meta-skin. When stretched, the meta-skin performs as a tunable frequency selective surface with a wide resonance frequency tuning range. When wrapped around a curved dielectric material, the meta-skin functions as a flexible “cloaking” surface to significantly suppress scattering from the surface of the dielectric material along different directions.
The microfluidic platform will find great applications when it integrates with other technologies. The development of such integration will greatly intersect different research areas and benefit all of the intersected technologies and fields, thus broadening the future applications
Recommended from our members
Chemistry and the Worm: Caenorhabditis elegans as a Platform for Integrating Chemical and Biological Research
This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools—biological, chemical, and physical—that are available to researchers studying the worm.Chemistry and Chemical Biolog
Multiview motion tracking based on a cartesian robot to monitor Caenorhabditis elegans in standard Petri dishes
[EN] Data from manual healthspan assays of the nematode Caenorhabditis elegans (C. elegans) can be complex to quantify. The first attempts to quantify motor performance were done manually, using the so-called thrashing or body bends assay. Some laboratories have automated these approaches using methods that help substantially to quantify these characteristic movements in small well plates. Even so, it is sometimes difficult to find differences in motor behaviour between strains, and/or between treated vs untreated worms. For this reason, we present here a new automated method that increases the resolution flexibility, in order to capture more movement details in large standard Petri dishes, in such way that those movements are less restricted. This method is based on a Cartesian robot, which enables high-resolution images capture in standard Petri dishes. Several cameras mounted strategically on the robot and working with different fields of view, capture the required C. elegans visual information. We have performed a locomotion-based healthspan experiment with several mutant strains, and we have been able to detect statistically significant differences between two strains that show very similar movement patterns.This work was supported by the research agency of the Spanish Ministry of Science and Innovation under Grant RTI2018-094312-B-I00 (European FEDER funds).Puchalt-Rodríguez, JC.; González-Rojo, JF.; Gómez-Escribano, AP.; Vázquez-Manrique, RP.; Sánchez Salmerón, AJ. (2022). Multiview motion tracking based on a cartesian robot to monitor Caenorhabditis elegans in standard Petri dishes. Scientific Reports. 12(1):1-11. https://doi.org/10.1038/s41598-022-05823-611112
Recommended from our members
Development of high-speed imaging techniques for C. elegans nervous system studies
We report high-speed imaging techniques for C. elegans nervous systems studies.
We introduce C. elegans, the main model organism in this dissertation, and neuroscientific and biomedical studies using C. elegans involving calcium imaging, nerve regeneration, and drug screening. We review technologies including confocal microscopy and microfluidic devices used in the neuroscientific and biomedical studies
We discuss development of a high-speed laser scanning confocal microscope capable of flexible control of imaging conditions, fast imaging speed, and large field-of-view. We provides the design principles used in the development of the confocal microscope including the optical, electrical, and software implementation, and the details of the confocal microscope we built based on the design principles. We present the performance characterization of the confocal microscope, then a few sample images obtained with the confocal microscope.
We present development of time-lapse volumetric confocal imaging of whole animal C. elegans Ca²⁺ dynamics. We provide the design of the time-lapse volumetric confocal imaging system including a microfluidic device to accommodate the whole animal within the field-of-view of the imaging system. We examine the feasibility of the volumetric confocal imaging of a whole animal, and demonstrate imaging of the whole animal C. elegans neurons’ response to NaCl within a 630 × 150 × 25 μm³ volume at 2 Hz rate.
We report a high-throughput automated imaging platform for C. elegans nerve regeneration study. We describe the design of the automated imaging platform and the automation flow, and characterizes the performance of the platform. The imaging platform can obtain high-resolution 3D confocal images of 20 animals in 10 minutes. We show sample images of C. elegans anterior lateral microtubule nerve regeneration examples acquired via the automated imaging platform.
We demonstrate a planar laser activated neuronal scanning platform (PLANS), a high-throughput animal examination system for drug screening. We explain the construction of PLANS involving the optics, the microfluidic device, and the electronics. The PLANS system can scan an animal in less than 5 ms with a spatial sampling resolution of 3 μm FWHM. We show sample scanning results of a Huntington’s disease model of C. elegans.
We summarize the studies discussed in this dissertation, and suggest relevant future research to follow up on the studies.Electrical and Computer Engineerin
- …