Lung-on-a-chip (LoC), also known as Lung Chips, are micro- and millifluidic organ-on-a-chip devices designed to replicate the structure and function of the human lung, mimicking the breathing motions and fluid dynamics that occur during inhalation and exhalation. [1] LoCs represent the most promising alternative to replace animal testing.
Huh et al. developed the first polydimethylsiloxane (PDMS)-based microfluidic system for culturing primary diseased small airway epithelial cells at the air-liquid interface (ALI). Despite its simplicity, this system successfully replicated crackling sounds associated with mechanical injury in the airway lumen. [2]
The first LoC, published in the June 25, 2010, issue of Science, was developed by Dan Huh and Donald E. Ingber at the Wyss Institute using a microfabrication technique called soft lithography, which was pioneered by George M. Whitesides. A typical alveolus LoC comprises two microchannels primarily lined with epithelial cells on the apical side and endothelial cells on the basal side. [3] Air is delivered to the lung lining cells, a culture medium flows in the capillary channel to mimic blood, and cyclic mechanical stretching is generated by a vacuum applied to the chambers adjacent to the cell culture channels to mimic breathing. The device is made using human lung and blood vessel cells and it can predict absorption of airborne nanoparticles and mimic the inflammatory response triggered by microbial pathogens. It can be used to test the effects of environmental toxins, absorption of aerosolized therapeutics, and the safety and efficacy of new drugs.
Since the introduction of LoCs in 2010, numerous advancements have been made to develop valid, functional, and clinically relevant models. [4]
The breathing movements in typical LoC such as Wyss platform occur in 2D, rather than the physiologically relevant three-dimensional (3D) format. Most organ-on-chip models, including LoC, are made from PDMS, which has several limitations. [5] For example, the two-compartment platform chip, similar to the Wyss chip, is at least 10-15 times thicker than its in vivo counterpart (the commercial Wyss chip has a thickness of 50 µm according to its datasheet). [6] This increased thickness is significant because it impedes the cross-talk between the two sides of the PDMS membranes.
The main issue with PDMS is its adsorption properties, which lead to unrealistic ADME and, consequently, inaccurate pharmacokinetics analysis. [5] [7] Other limitations of PDMS include biodegradation, leaching, cell delamination, and molecule absorption, all of which affect the accuracy and reliability of cell assays. [8]
Microfluidics refers to a system that manipulates a small amount of fluids using small channels with sizes of ten to hundreds of micrometres. It is a multidisciplinary field that involves molecular analysis, molecular biology, and microelectronics. It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening. Microfluidics emerged in the beginning of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies.
A surface acoustic wave (SAW) is an acoustic wave traveling along the surface of a material exhibiting elasticity, with an amplitude that typically decays exponentially with depth into the material, such that they are confined to a depth of about one wavelength.
A lab-on-a-chip (LOC) is a device that integrates one or several laboratory functions on a single integrated circuit of only millimeters to a few square centimeters to achieve automation and high-throughput screening. LOCs can handle extremely small fluid volumes down to less than pico-liters. Lab-on-a-chip devices are a subset of microelectromechanical systems (MEMS) devices and sometimes called "micro total analysis systems" (μTAS). LOCs may use microfluidics, the physics, manipulation and study of minute amounts of fluids. However, strictly regarded "lab-on-a-chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "μTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis.
Polydimethylsiloxane (PDMS), also known as dimethylpolysiloxane or dimethicone, is a silicone polymer with a wide variety of uses, from cosmetics to industrial lubrication and passive daytime radiative cooling.
Organ printing utilizes techniques similar to conventional 3D printing where a computer model is fed into a printer that lays down successive layers of plastics or wax until a 3D object is produced. In the case of organ printing, the material being used by the printer is a biocompatible plastic. The biocompatible plastic forms a scaffold that acts as the skeleton for the organ that is being printed. As the plastic is being laid down, it is also seeded with human cells from the patient's organ that is being printed for. After printing, the organ is transferred to an incubation chamber to give the cells time to grow. After a sufficient amount of time, the organ is implanted into the patient.
Plasma cleaning is the removal of impurities and contaminants from surfaces through the use of an energetic plasma or dielectric barrier discharge (DBD) plasma created from gaseous species. Gases such as argon and oxygen, as well as mixtures such as air and hydrogen/nitrogen are used. The plasma is created by using high frequency voltages to ionise the low pressure gas, although atmospheric pressure plasmas are now also common.
Alternatives to animal testing are the development and implementation of test methods that avoid the use of live animals. There is widespread agreement that a reduction in the number of animals used and the refinement of testing to reduce suffering should be important goals for the industries involved. Two major alternatives to in vivo animal testing are in vitro cell culture techniques and in silico computer simulation; however, some claim they are not true alternatives because simulations use data from prior animal experiments and cell cultures often require animal derived products, such as serum or cells. Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems.
Ali Khademhosseini is an Iranian-born Canadian-American engineer. He is the CEO of the Terasaki Institute, non-profit research organization in Los Angeles, and Omeat Inc., a cultivated-meat startup. Before taking his current CEO roles, he spent one year at Amazon Inc. Prior to that he was the Levi Knight chair and professor at the University of California-Los Angeles where he held a multi-departmental professorship in Bioengineering, Radiology, Chemical, and Biomolecular Engineering as well as the Director of Center for Minimally Invasive Therapeutics (C-MIT). From 2005 to 2017, he was a professor at Harvard Medical School, and the Wyss Institute for Biologically Inspired Engineering.
Bio-MEMS is an abbreviation for biomedical microelectromechanical systems. Bio-MEMS have considerable overlap, and is sometimes considered synonymous, with lab-on-a-chip (LOC) and micro total analysis systems (μTAS). Bio-MEMS is typically more focused on mechanical parts and microfabrication technologies made suitable for biological applications. On the other hand, lab-on-a-chip is concerned with miniaturization and integration of laboratory processes and experiments into single chips. In this definition, lab-on-a-chip devices do not strictly have biological applications, although most do or are amenable to be adapted for biological purposes. Similarly, micro total analysis systems may not have biological applications in mind, and are usually dedicated to chemical analysis. A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions. The interdisciplinary nature of bio-MEMS combines material sciences, clinical sciences, medicine, surgery, electrical engineering, mechanical engineering, optical engineering, chemical engineering, and biomedical engineering. Some of its major applications include genomics, proteomics, molecular diagnostics, point-of-care diagnostics, tissue engineering, single cell analysis and implantable microdevices.
Donald E. Ingber is an American cell biologist and bioengineer. He is the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. He is also a member of the American Institute for Medical and Biological Engineering, the National Academy of Engineering, the National Academy of Medicine, the National Academy of Inventors, and the American Academy of Arts and Sciences.
An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture, integrated circuit (chip) that simulates the activities, mechanics and physiological response of an entire organ or an organ system. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context. By acting as a more sophisticated in vitro approximation of complex tissues than standard cell culture, they provide the potential as an alternative to animal models for drug development and toxin testing.
Microfluidics in chemical biology is the application of microfluidics in the study of chemical biology.
An off-stoichiometry thiol-ene polymer is a polymer platform comprising off-stoichiometry thiol-enes (OSTE) and off-stoichiometry thiol-ene-epoxies (OSTE+).
Microfluidic cell culture integrates knowledge from biology, biochemistry, engineering, and physics to develop devices and techniques for culturing, maintaining, analyzing, and experimenting with cells at the microscale. It merges microfluidics, a set of technologies used for the manipulation of small fluid volumes within artificially fabricated microsystems, and cell culture, which involves the maintenance and growth of cells in a controlled laboratory environment. Microfluidics has been used for cell biology studies as the dimensions of the microfluidic channels are well suited for the physical scale of cells. For example, eukaryotic cells have linear dimensions between 10 and 100 μm which falls within the range of microfluidic dimensions. A key component of microfluidic cell culture is being able to mimic the cell microenvironment which includes soluble factors that regulate cell structure, function, behavior, and growth. Another important component for the devices is the ability to produce stable gradients that are present in vivo as these gradients play a significant role in understanding chemotactic, durotactic, and haptotactic effects on cells.
Surface tension is one of the areas of interest in biomimetics research. Surface tension forces will only begin to dominate gravitational forces below length scales on the order of the fluid's capillary length, which for water is about 2 millimeters. Because of this scaling, biomimetic devices that utilize surface tension will generally be very small, however there are many ways in which such devices could be used.
Droplet-based microfluidics manipulate discrete volumes of fluids in immiscible phases with low Reynolds number and laminar flow regimes. Interest in droplet-based microfluidics systems has been growing substantially in past decades. Microdroplets offer the feasibility of handling miniature volumes of fluids conveniently, provide better mixing, encapsulation, sorting, sensing and are suitable for high throughput experiments. Two immiscible phases used for the droplet based systems are referred to as the continuous phase and dispersed phase.
Microfluidics refers to the flow of fluid in channels or networks with at least one dimension on the micron scale. In open microfluidics, also referred to as open surface microfluidics or open-space microfluidics, at least one boundary confining the fluid flow of a system is removed, exposing the fluid to air or another interface such as a second fluid.
Open microfluidics can be employed in the multidimensional culturing of cell types for various applications including organ-on-a-chip studies, oxygen-driven reactions, neurodegeneration, cell migration, and other cellular pathways.
Intestines-on-a-chip are microfluidic bioengineered 3D-models of the real organ, which better mimic physiological features than conventional 3D intestinal organoid culture. A variety of different intestine-on-a-chip models systems have been developed and refined, all holding their individual strengths and weaknesses and collectively holding great promise to the ultimate goal of establishing these systems as reliable high-throughput platforms for drug testing and personalised medicine. The intestine is a highly complex organ system performing a diverse set of vital tasks, from nutrient digestion and absorption, hormone secretion, and immunological processes to neuronal activity, which makes it particularly challenging to model in vitro.
The Wyss Institute for Biologically Inspired Engineering is a cross-disciplinary research institute at Harvard University focused on bridging the gap between academia and industry by drawing inspiration from nature's design principles to solve challenges in health care and the environment. It is focused on the field of biologically inspired engineering to be distinct from bioengineering and biomedical engineering. The institute also has a focus on applications, intellectual property generation, and commercialization.