Research 01 November Open Access. Research 29 October Open Access. Single-cell proteomics is an emerging technology but protein coverage, throughput and quantitation accuracy are often still insufficient.
Here, the authors develop a nested nanowell chip that improves protein recovery, throughput and robustness of isobaric labeling-based quantitative single-cell proteomics.
Research 26 October Open Access. Chronic desynchronization between physiological and behavioral rhythms has been linked to the onset of metabolic diseases. Here the authors control the cyclic metabolic signals in a microfluidic device to study the effects of the timing, period and frequency of glucose and insulin on the transcriptome of cultured fibroblasts.
Correspondence 13 October A microwell chip facilitates the differentiation of aggregates of human induced pluripotent stem cells into pancreatic-duct-like organoids and the characterization of the differentiation process at the single-cell level.
For genome-wide screens and other applications that require the processing of a large number of cells, the immunomagnetic sorting of cells on a microfluidic chip is a scalable, rapid and cost-efficient alternative to fluorescence-activated cell sorting. Research Highlights 27 June Early lab-on-a-chip research also focused on cell biology.
This is not surprising when considering that the microchannels were the same scale size as cells. These advances allowed scientists to easily perform operations at the single cell level for the first time. Much research has been done on the miniaturization of genomic biochemical operations such as PCR, electrophoresis, DNA microarray, pretreatment step, cell lysis, etc. Eventually, researchers began to integrate all the required steps from sample collection to final analysis onto the same chip, showing the real potential of lab-on-a-chip technologies.
Military agencies such as the DARPA and the DGA were soon interested in lab-on-a-chip technologies since such advancements would allow them to detect biological threats towards troops and civilians as soon as possible. About 30 years before with semiconductors and space exploration programs, these agencies invested a lot of money in advancing research on lab-on-a-chip. For some applications, lab-on-a-chip not only shows the capacity of integration and parallelization, but also demonstrates superior performance compared to conventional technologies.
Much research has been conducted on lab-on-a-chip. Here are some examples of applications where lab-on-a-chip shows great promises. Since DNA amplification using PCR relies on thermal cycles, the ability to perform high-speed thermal shifts at the microscale explains why lab-on-a-chip became the fastest way of doing PCR. The first human genome projects took years and required the work of hundreds of researchers to sequence.
Today, using lab-on-a-chip to integrate an array of DNA probes, we are able to sequence genomes thousands of times faster. Moreover, nanopore technologies, which still need to be optimized, hold great potential in the future for being much faster for genome sequencing than actual lab-on-a-chip using an array of DNA probes. All the biomolecular operations done in labs-on-a-chip show great potential for ultra-fast bacteria and virus detection, but also for disease biomarker identification DNA and RNA.
Additionally, labs-on-a-chip solutions hold enormous possibilities for immunoassays, which can be done in tens of seconds instead of ten minutes as when using macroscopic technologies.
In the field of molecular separation too, labs-on-a-chip demonstrate more efficient separation than with conventional systems. In the field of proteomics, lab-on-a-chip provides the opportunity to perform protein analysis while integrating all the steps within the same chip: extraction from the cell, separation by electrophoresis, digestion and analysis using mass spectrometry.
These integrated processes show the ability to greatly shorten protein analysis from hours, with macroscopic system, to a few minutes with lab-on-a-chip devices. They also show great potential for protein crystallization which is an important research field that reveals the 3D structure of a protein. Using lab-on-a-chip, researchers are able to control simultaneously and in the fastest way possible all the parameters enabling the crystallization of a given protein.
It is then possible to greatly parallelize crystallization conditions in order to speed up the discovery of these conditions for unknown proteins and study their structures using X-ray diffraction. Since microchannels are the same typical size as cells, lab-on-a-chip research soon focused on cell biology.
Lab-on-a-chip demonstrates the ability to control cells at the single-cell level while dealing with a large number of them in seconds. At the microscale level, flow switch can be very fast and goes down to just tens of milliseconds. For example, For example, one can detect and isolate a given cell, such as cancerous cell made fluorescent using antibodies with high throughput. There are several other applications for lab-on-a-chip in cell biology , including micro patch clamp, control of stem cell differentiation, high-speed flow cytometry , sperm sorting and more generally cell sorting.
The ability to perform fast heating and cooling at the microscale allows for higher efficiency in some chemical reactions. Therefore, much research has been conducted on using labs-on-a-chip as microsized and highly parallelized micro chemical reactors. Lab-on-a-chip devices can also be of interest when dealing with dangerous and explosive compounds in that they contain risks by dealing with smaller volumes at a time. Lab-on-a-chip uses the most common microfluidic device manufacturing technologies , and depending on their applications, various polymers.
Such technologies enable the integration of microchannels with micrometer scale sizes. PDMS polydimethylsiloxane is a transparent and flexible elastomer that is widely used because it is very easy and cheap to fabricate PDMS labs-on-a-chip by casting.
Moreover, labs-on-a-chip made of PDMS take advantage of, the easy integration of quake microvalves for fast flow switch and, permeability of air for cell culture and studies. Widely used for lab-on-a-chip prototyping, PDMS shows severe limitations for industrial production.
Finally, PDMS is not compatible with high throughput chip fabrication process such as hot embossing or injection molding. Even if it is a little bit trickier and more expensive to implement than PDMS, thermoplastics are good candidates for the fabrication of labs-on-a-chip since they are transparent, compatible with micrometer-sized lithography and are more chemically inert than PDMS.
For certain applications, some research teams obtained very good results with thermoplastic labs-on-a-chip, and since it is possible to integrate microelectrodes into them, thermoplastic materials can be good candidates for the industrialization of some labs-on-a-chip. Glass : Transparent, compatible with micrometer sized machining, chemically inert, with a wide range of well-known chemical surface treatments and reproducible electrode integration, glass is a very good candidate for the industrialization of labs-on-a-chip.
From a research point of view, the fabrication of glass labs-on-a-chip requires clean rooms and researchers with a strong knowledge of microfabrication. Thus, glass lab-on-a-chip are not available to all research labs. Silicon : The first lab-on-a-chip was made of silicon , and it seems like a normal choice since microtechnologies are based on the microfabrication of silicon chips.
Nowadays researchers do not often use silicon for labs-on-a-chip, mainly because silicon is expensive, not optically transparent except for IR and requires a clean room as well as a strong knowledge of microfabrication. Moreover, the electrical conductivity of silicon makes it impossible to use for lab-on-a-chip operations requiring high voltage like electrophoresis.
Still, even if nowadays silicon seems like an obsolete candidate for the industrialization of lab-on-a-chip, we believe it may still be a relevant choice for the industrialization of some demanding lab-on-a-chip applications. This assumption takes into account the high precision of silicon microfabrication, the maturity of the process, the investments put into the silicon industry, and the ability to integrate any kind of microelectrode and even electronics on the same chip,.
Paper : Lab-on-a-chip devices based on paper technologies may have strong outcomes for applications requiring ultra-low costs. Supported by G. Whiteside, one of the most famous microfluidic researchers, paper labs-on-a-chip may find their market in the future. We hope it will, as the idea is very seducing and could open up the field of diagnostics and make it accessible to lower-income and limited-resource populations. Picture from Wyss institute. Low cost: Microtechnologies will decrease the cost of analysis much like they decreased the cost of computed calculation.
Integration will allow numerous tests to be performed on the same chip, reducing to a negligible price the cost of each individual analysis. High parallelization: Thanks to its capacity for integrating microchannels, lab-on-a-chip technology will allow tens or hundreds of analyses to be performed simultaneously on the same chip. This will allow doctors to target specific illnesses during the time of a consultation in order to prescribe quickly and effectively the best-suited antibiotic or antiviral.
Ease of use and compactness: Lab-on-a-chip allows the integration of a large number of operations within a small volume. In the end, a chip of just a few centimeters square coupled with a machine as small as a computer will allow for analyses comparable to those conducted in full analytical laboratories. Diagnostics using lab-on-a-chip will require a lot less handling and complex operations andin most cases, they will be able to be performed on site by a nurse.
Reduction of human error: Since it will strongly reduce human handling, automatic diagnoses done using lab-on-a-chip will greatly reduce the risk of human error compared with classical analytical processes done in laboratories. Faster response time and diagnosis: At the micrometric scale, diffusion of chemicals, flow switch and diffusion of heat is faster. One can change the temperature in hundreds of ms which enables, for example, faster DNA amplification using PCR or the mixing of chemicals by diffusion in seconds to enable faster biochemical reactions, for example.
Low volume samples: Because lab-on-a-chip systems only require a small amount of blood for each analysis, this technology will decrease the cost of analysis by reducing the use of expensive chemicals. Last but not the least, it will allow to detect of a high number of illnesses without requiring large quantities of blood from patients. Real time process control, and monitoring, increase sensitivity: Thanks to fast reactivity at the microscale, one can control in real time the environment of a chemical reaction in the lab-on-a-chip, leading to more controlled results.
Expendable: Due to their low price, automation and low energy consumption, lab-on-a-chip devices will also be able to be used in outdoor environments for air and water monitoring without the need for human intervention. Share the health with everybody: Lab-on-a-chip will reduce diagnostic costs, the training of medical staff and the cost of infrastructure.
As a result, lab-on-a-chip technology will make modern medicine more accessible to developing countries at reasonable costs. In one sentence: We can clearly expect lab-on-a-chip to save numerous lives. Industrialization: Most lab-on-a-chip technologies are not yet ready for industrialization.
Regarding its core application, the ultra-multiplex diagnosis, at this time we are not certain which fabrication technologies will become the standard. Ethics and human behavior: Without regulations, real-time processing and the widespread accessibility of labs-on-a-chip may generate some fears of the untrained public diagnosing potential infections at home.
Moreover, the DNA sequencing potential of lab-on-a-chip may enable anyone to sequence the DNA of others using a drop of saliva. Lab-on-a-chip needs an external system to work: Even if lab-on-a-chip devices can be small and powerful, they require specific machinery such as electronics or flow control systems to be able to work properly.
Without a precise system to inject, split and control the positioning of samples, labs-on-a-chip are useless.
External devices increase the final size and cost of the overall system and some, particularly flow control equipment, can often pose limitations for lab-on-a-chip performance. We have a complete brand of high-precision flow control systems for lab-on-a-chip. Sens Actuators B — Google Scholar. Whitesides GM The origin and future of microfluidics. Nature — Google Scholar. Rev Mod Phys 77 3 — Google Scholar. Jose L. Garcia-Cordero 1 Antonio J. Ricco 1 1.
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