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Lab-on-Chip devices allow faster and cheaper DNA sequencing and biochemical detection to chemical synthesis

Lab-on-chip  is an integrated miniaturized device  that  allows researchers to perform all the operations  from sample collection to final analysis onto the same chip. Theoretically, LOC technology has the potential to carry out almost any laboratory procedure on a miniaturized scale. This could range from DNA sequencing and biochemical detection to chemical synthesis, clinical diagnostics and biomarker validation. The basis of the lab-on-a-chip dream is to integrate onto a single micro-process chip thousands of biochemical operations that could be done by splitting a single drop of blood collected from the patient in order to get a precise diagnosis of potential diseases.


Lab-on-a-chip devices are a subset of microelectromechanical systems (MEMS) devices and sometimes called “micro total analysis systems” (µTAS). Lab-on-a-chip technology essential comprises devices which have an element that is millimeter to centimeter sizes which encapsulate more than one laboratory processes into a singular device. LOCs may use microfluidics, the physics, manipulation and study of minute amounts of fluids. LOCs can handle extremely small fluid volumes down to less than pico-liters.


In the case of LOC technology, microfluidics relates to the study of the behavior of fluids through micro-channels and the manufacturing of miniaturized devices containing chambers and tunnels through which liquids flow. Such devices typically comprise microfluidic elements for fluid handling and additional components for fluid control, processing and some detection capability. LOC might include biosensors/electrochemical/optochemical sensors that have been developed in recent years.

Lab-on-Chip Breakthroughs allow them to detect faster, cheaper and less invasively | International Defense Security & Technology Inc.

Microfluidic devices can integrate sample preparation and detection on microassays, scaling down different laboratory functions onto one chip. For instance, in cell biology, researchers are able to culture their cells within a microfluidic device with the possibility to inject drugs and see live the response of the sample at a cellular basis. In this regard, the possibility to have complete control over the surrounding environment has been deeply explored. This approach can be a game changer in applications  ranging from cancer research to defense against chemical agents, and it holds the promise of providing orders of magnitude advantage in speed and cost.


Several labs-on-a-chip have been commercialized for some key applications such as glucose monitoring, HIV detection or heart attack diagnostics. The challenge for industrial research will be to incorporate on the same lab-on-a-chip the maximum amount of individual operations in order to decrease costs and increase ergonomics as well as the speed of diagnosis. At the moment, technologies are not unified and nobody can say which technologies and which materials will be the most promising for high throughput diagnostics. For example, in February 2016, researchers at the University of Kansas developed a new chip laboratory diagnostic device that adjusted the
liquid biopsy principle to detect cancer using plasma or blood drops quickly.


Military agencies such as the DARPA and the DGA have also invested a lot of money in advancing research on lab-on-a-chip technologies since such advancements would allow them to detect biological threats towards troops and civilians as soon as possible.

Laboratory-on-a-chip Advantages

Miniaturization of biochemical operations normally handled in a laboratory has numerous advantages, such as cost efficiency, parallelization, ergonomy, diagnostic speed and sensitivity.  LOC technology enables the use of small fluid volumes which helps cut costs and the analysis of reagents and response time. It also allows greater control over sample concentrations as well as interactions to reduce the quantity of chemical waste.


Thanks to its capacity for integrating microchannels, lab-on-a-chip technology will allow tens or hundreds of analysis 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.


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).


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.


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. 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.


In a near future, lab-on-a-chip devices, with their ability to perform complete diagnosis of a patient during the time of a consultation, will change our way of practicing medicine. Diagnosis will be done by people with lower qualifications, thus enabling doctors to focus only on treatment. Real time diagnosis will increase the chances of survival for patients in emergency services and will allow the appropriate treatment to be given to each patient.


Current Challenges and Research

However, LOC is an emerging technology and has a few disadvantages. The physical and chemical effects such as surface roughness, capillary forces, and chemical interactions between materials are more significant at the microscale level. This can often result in complications during LOC experiments which would not be expected with traditional lab equipment.


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. For some applications miniaturization can result in a low signal/noise ratio and as a result, lab-on-a-chip provides poorer results than conventional techniques.


Another challenges is the increase in the maximum number of biological operations able to be integrated on the same chip and the increase in parallelization to achieve the detection of hundreds of pathogens in the same microfluidic cartridge.  Fundamental research on certain technologies with a high potential impact, such as DNA reading through nanopore, which requires more investigation in order to be applicable.


However, to date very few devices have attained commercial success. This challenges relate to the commercialization of lab-on-a-chip technology from fundamental research to mass manufacturing.  This includes the adaptation of fabrication processes, the design of specific surface treatments, flow control system … etc…To date, the main roadblock to the widespread use and development of LOC devices has been the successful design and fabrication of functional, cost-effective systems. Most lab-on-a-chip technologies are not yet ready for industrialization and commercial use.


Optical Diagnostic Platform Detects Multiple Viruses reported in Jan 2021

University of Rochester researchers are developing an optical chip on a disposable card that is capable of detecting exposure to multiple viruses, within a minute and from a single drop of blood. “This is a completely new diagnostic platform,” said Miller, Dean’s Professor of Dermatology and a professor of biomedical engineering, optics, and biochemistry and biophysics. “We think this is going to be valuable in very broad applications for clinical diagnostics, not just COVID-19.”


The core of the technology is an optical chip no larger than a grain of rice. Proteins associated with eight different viruses, including SARS-CoV-2, are contained in separate sensor areas of the chip. If the sample is positive for any of the viruses, antibodies to those viruses in the blood sample will be drawn to the proteins and detectable. The technology may allow clinicians to better understand potential relationships between COVID-19 infection and immunity to other respiratory viruses, including circulating coronaviruses that cause the common cold.


The researchers plan to use blood drawn from 100 consenting convalescent COVID-19 patients to test the device’s effectiveness. Once the prototype has been completed and validated, the researchers will be eligible to apply for further funding to move the technology closer to commercial availability.


Breakthrough ‘Lab-On-A-Chip’ Detects Cancer Faster, Cheaper and Less Invasively reported in Feb 2019

A new ultrasensitive diagnostic device invented by researchers at the University of Kansas, The University of Kansas Cancer Center and KU Medical Center could allow doctors to detect cancer quickly from a droplet of blood or plasma, leading to timelier interventions and better outcomes for patients.

Breakthrough 'lab-on-a-chip' detects cancer faster, cheaper and less invasively | The University of Kansas

The “lab-on-a-chip” for “liquid biopsy” analysis, reported in Nature Biomedical Engineering in Feb 2019, detects exosomes — tiny parcels of biological information produced by tumor cells to stimulate tumor growth or metastasize.


“Historically, people thought exosomes were like ‘trash bags’ that cells could use to dump unwanted cellular contents,” said lead author Yong Zeng, Docking Family Scholar and associate professor of chemistry at KU. “But in the past decade, scientists realized they were quite useful for sending messages to recipient cells and communicating molecular information important in many biological functions. Basically, tumors send out exosomes packaging active molecules that mirror the biological features of the parental cells. While all cells produce exosomes, tumor cells are really active compared to normal cells.”


The new lab-on-a-chip’s key innovation is a 3D nanoengineering method that mixes and senses biological elements based on a herringbone pattern commonly found in nature, pushing exosomes into contact with the chip’s sensing surface much more efficiently in a process called “mass transfer.”

“People have developed smart ideas to improve mass transfer in microscale channels, but when particles are moving closer to the sensor surface, they’re separated by a small gap of liquid that creates increasing hydrodynamic resistance,” Zeng said. “Here, we developed a 3D nanoporous herringbone structure that can drain the liquid in that gap to bring the particles in hard contact with the surface where probes can recognize and capture them.”


Zeng compared the chip’s nanopores to a million little kitchen sinks: “If you have a sink filled with water and many balls floating on the surface, how do you get all the balls in contact with the bottom of the sink where sensors could analyze them? The easiest way is to drain the water.”


Researchers Develop ‘Lab On A Chip’ For Personalized Drug Efficacy Monitoring reported in Nov 2019

UCI researchers and collaborators have developed a “lab on a chip” platform to facilitate continuous, inexpensive, rapid and personalized drug screening. The technology is capable of evaluating the effectiveness of treatments on cancer cells without bulky readout equipment or requiring the shipment of samples to labs.


The lab-on-a-chip technology employs advanced electrical and electrochemical techniques to precisely manipulate cancer cells of interest in parallel with the continuous characterization of the potential effectiveness of therapeutic agents custom-made for patients. The end result should greatly reduce the time and cost associated with treating cancer.

Researchers develop 'lab on a chip' for personalized drug efficacy monitoring | UCI News | UCI

“There is an ever-present need for simplified and low-cost identification of a patient’s personal cancer resistance and medication efficacy before and throughout treatment,” said senior author Rahim Esfandyarpour, UCI assistant professor of electrical engineering & computer science, as well as biomedical engineering. “We envision our work as another step toward potentially enabling the personalized screening of drug efficacy on individual patients’ samples, possibly leading us to a better understanding of drug resistance and the optimization of patients’ treatments.” He said that most current approaches to drug efficacy testing require expensive imaging, lab work and large-scale cell culture experiments.

Scientists develop ‘lab on a chip’ that costs 1 cent to make reported in 2017

Researchers at the Stanford University School of Medicine have developed a way to produce a cheap and reusable diagnostic “lab on a chip” with the help of an ordinary inkjet printer. “Enabling early detection of diseases is one of the greatest opportunities we have for developing effective treatments,” Esfandyarpour said. “Maybe $1 in the U.S. doesn’t count that much, but somewhere in the developing world, it’s a lot of money.

Scientists develop 'lab on a chip' that costs 1 cent to make | News Center | Stanford Medicine

A combination of microfluidics, electronics and inkjet printing technology, the lab-on-a-chip is a two-part system: A clear silicone microfluidic chamber for housing cells sits on top of a reusable electronic strip. A regular inkjet printer that can be used to print the electronic strip onto a flexible sheet of polyester using commercially available conductive nanoparticle ink.


Designed as a multifunctional platform, one of its applications is that it allows users to analyze different cell types without using fluorescent or magnetic labels that are typically required to track cells. Instead, the chip separates cells based on their intrinsic electrical properties: When an electric potential is applied across the inkjet-printed strip, cells loaded into the microfluidic chamber get pulled in different directions depending on their “polarizability” in a process called dielectrophoresis. This label-free method to analyze cells greatly improves precision and cuts lengthy labeling processes.


The tool is designed to handle small-volume samples for a variety of assays. The researchers showed the device can help capture single cells from a mix, isolate rare cells and count cells based on cell types.


The low cost of the chips could democratize diagnostics similar to how low-cost sequencing created a revolution in health care and personalized medicine, Davis said. Inexpensive sequencing technology allows clinicians to sequence tumor DNA to identify specific mutations and recommend personalized treatment plans. In the same way, the lab on a chip has the potential to diagnose cancer early by detecting tumor cells that circulate in the bloodstream. “The genome project has changed the way an awful lot of medicine is done, and we want to continue that with all sorts of other technology that are just really inexpensive and accessible,” Davis said.


The technology has the potential to not only advance health care, but also to accelerate basic and applied research. It would allow scientists and clinicians to potentially analyze more cells in shorter time periods, manipulate stem cells to achieve efficient gene transfer and develop cost-effective ways to diagnose diseases, Esfandyarpour said. The team hopes the chip will create a transformation in how people use instruments in the lab. “I’m pretty sure it will open a window for researchers because it makes life much easier for them — just print it and use it,” he said.


Lab-on-chips Market

The size of the global lab on a chip market is expected to reach 9.06 billion by 2025, growing at a CAGR of 8.9% between 2020 to 2025.
Lab-on-a-Chip has several laboratory functions in a single integrated chip. Lab-on-achip is fabricated through a process called photolithography. This is superior in consuming low fluid and works efficiently with a faster response time. Point of care testing devices is highly dependent on these integrated chips to provide adequate healthcare. This technology is based on a complex biosensor system and uses a small metal layer embedded in a microchip to eliminate the cumbersome and complicated optics used in diagnostic laboratories.


Biochips are increasingly used in the fields of biomedical and biotechnology research. Advances in technology in the medical field are increasing the adoption rate of biochips in proteomics (such as microarrays). The advantages of protein biochips include low sample consumption and a tendency to miniaturize. For example, protein microarrays can display multiple proteins simultaneously, and these properties translate into the ability to process thousands of samples in parallel. This feature of microarrays is important for proteomewide analysis. Proteomics is widely used for biomarker and drug discovery.


Market Drivers

In Lab On a Chip Market, the increasing adoption of personalized medicine, increasing research in drug discovery and life sciences, and the need for rapid diagnostics are factors driving the development of chip labs. R&D investment growth in developing countries is expected to provide significant opportunities for crucial lab on a chip market participant throughout the forecast period


The rise in the incidences of many health disorders is accelerating the demand of the Lab on a Chip Market. Increasing support from the semiconductor industry in launching innovative circuits for the medical sector is propelling the market’s need.  Other factors drive the development of the chip lab and microarray (biochip) markets, including increased use of biochips in cancer treatment and diagnosis, the demand for personalized medicine, and rapid advances in biochip technology.


Lab Chip devices are influencing the Laboratory Testing market where trace samples are to be analysed in the field if medical examination. Being handy, portable, and easy to use these devices are extensively used in hospitals and various surgical centres as well, thus promising the growth of global Lab Chip Devices Market in the near future.


Market Restraints

However, the high cost of equipment for installation and maintenance is restraining the demand of the market. The government’s stringent rules and regulations have remained a challenging factor for the global lab on a chip market. The costs and low commercial acceptance due to a shortage of skilled workers are also hindering the market.


Diagnostics will hold the largest segment globally, because of the growing demand for diagnostics with high speed, efficiency, and sensitivity of results with accuracy. Diagnostics segment is expected to expand at the highest CAGR of 11.3% over the period from 2018 to 2026. Day by day increasing global population is continuously increasing the number of patients with diseases and thus the demand for microfluidic systems for diagnosis, treatment, and monitoring of these diseases. The Lab on chips contributes to the rise in personalized medicine, drug discovery and life science research, and growing need for high speed diagnostics. These factors will lead the diagnostics segment across different regions of the world.


Regionally, North America is accounted for holding the largest shares of the market due to the quick adoption of the latest technological developments and innovative products in favor of the end-users. The Asia Pacific and Europe are next to North America to lead with
the highest shares of the market with the rise in the government’s investments in hospitals. The Middle East and Africa are to have a significant growth rate in foreseen years.


In North America, market players are developing advanced microfluidic products continuously. The U.K. holds highest share in Europe market with a significant growth. Whereas in APAC, the demand is mainly concentrated in China and India, due to the increasing population and popularity of conventional biological laboratories.


Some of the key players in the global lab-on-chips application market areare Becton Dickinson and Company, PerkinElmer, Inc., Danaher Corporation, Bio-Rad Laboratories, Thermo Fisher Scientific, F. Hoffmann-La Roche AG, Agilent Technologies, Inc., Abbott Laboratories, Fluidigm Corporation, RainDance Technologies, Inc. , IDEX Corporation,  EMD Millipore, Life Technologies Corporation, Abbott Laboratories, Roche Diagnostics, and Siemens Healthcare.




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