Lab-on-a-Chip Technology: Innovations, Applications, and Future Trends

Lab-on-a-chip (LOC) is Lab-on-Chip technology implies those techniques that perform various laboratory operations on  a  miniaturized  scale  such  as  chemical  synthesis  and  analysis  on  a single  chip  leading  to  a  handheld  and  portable  device.  Thus, LoC is the device that can translate the one or several functions of the laboratory into a chip. The size of the chip varies from millimetres to a few square centimetres. It is applied in areas such as diagnostics, biotechnology, environmental and bioremediation, and drug discovery. LOC devices are employed for point of care testing, diagnostics for diseases like diabetes, infectious diseases, and cancers among them. LOC systems are able to differentiate toxins, pollutants, or pathogens in water, air or soil and samples taken from such. The claim involving decreased time and cost in drug discovery is coupled with the use of miniaturized platforms for the portrayal of drugs and cellular responses in the pursuit.

• Miniaturization: Reducing the analysed processes to microscale which results in the faster rates of the reaction and smaller quantities of samples needed.
• Automation: The extent to which repetitive sequences in laboratories can be minimized within automation systems.
• Integration: Combining different operations (sample preparation, reaction, detection) on one chip in order to ease up the process.
• Portability: Compactness allows these devices to be portable, offering field-based applications for diagnostics or environmental analysis.

The technology has its roots back in microfabrication processes utilized for microelectronics, during the 1950s and 1960, where photolithography was employed to produce micro-scale transistors. The first real LOC was built in the mid 1970’s at Stanford University for gas chromatography, however more work into LOC did not emerge until the late 1980’s with the advent of micro fluidics and soft lithography. Its importance increased in the 1990s when researchers downsized biochemical operations and initiated the micro total analysis system (µTAS), encapsulating each stage of a laboratory procedure on a chip. It also provided the capabilities of doing operation as single cell analysis, making its application in cell biology and diagnostics.

Today, enhanced LOC devices are employed in point of care, diagnostics, pharmaceutical research, genomics and environmental control. Changes for fabrication include soft lithography and stand alone fabrication stations also make it possible for labs to build LOC systems on demand without having to access expensive clean room facilities making the LOC technology accessible for research and use practically the world over.

Technologies in Lab-on-a-Chip (LOC)

Microfluidics

Microfluidics is the main technology that allows manipulation and controlling of small volume of fluids (from microliters to picoliters) inside microchannels that are integrated into the chip. The size of the LOC systems, make fluids in the systems to flow in a laminar manner as opposed to the turbulent nature of fluids in larger systems.

• Microchannels:Microfluidic networks consisting of thin and deep features on the chip that transport small volume of liquids from microliters to even picolitre’s.
• Capillary Action: The process of fluid transport through microscale conduits without a requirement for external pumping.
• Pressure-driven Flow:The movement of fluids through a chip may be done by external pumps, a pressure or vacuum system.
• Electrokinetic Flow:Methods like electrophoresis and electroosmosis that help in the manipulating the motion of fluids or particles in microchannels by applying an electric field.

Microfabrication Techniques

LOC devices are made using a set of microfabrication techniques adopted from integrated circuit technologies. These include:

• Photolithography: A technology in which the control of light waves guides a material (normally silicon or glass) to deposit a patterned surface. It is one of the fundamental steps to formulate microfluidic channels and other features in the chip.
• Soft Lithography: A reusable, inexpensive technology for microfabrication based on the material polydimethylsiloxane (PDMS). Soft lithography results in the formation of easy to fabricate flexible LOC devices and is the most widely used fabrication technique in LOC research.
• Injection Molding: This equipment is employed in mass production of LOC devices derived from thermoplastic polymers, including polycarbonate and PMMA.
• 3D Printing: Rising as a versatile fabrication technique for constructing LOC devices with complicated features and structures.

Microelectronics and Sensors

LOC devices allow for the use of different types of sensors and electronics for analyte reactions on the chip level. These include:

• Optical Sensors: The major choice in fluorescence or absorbance detection, which enables kinetic control over chemical and biological processes.
• Electrical Sensors: Analytical electrochemical sensors can either be used to monitor a change in the chemical environment or for a quantitative determination of the concentration of analytes using electrical signals.
• Thermal Sensors: Used to check on temperature sensitive reactions such as Polymerase Chain Reaction (PCR) for the amplification of DNA.
• Magnetic Sensors: Helpful in devices where magnetophoretic is employed player to separate particles for instance, magnetic bead-based assays).

Polymerase Chain Reaction (PCR) on Chip

Some of the key operations, which have been incorporated in LOC devices are the miniaturized processes of the Polymerase Chain Reaction (PCR) which is utilized to amplify DNA among other processes. Technologies include:

• Thermal Cycling: LOC devices use tiny thermal cyclers that enable quick changing of temperature for the DNA samples in PCR process in a much smaller manner.
• Digital PCR: Through PCR, LOC devices are capable of determining the exact quantity of DNA together within many microfluidic compartments at the same time.

Nanotechnology

Nanotechnology is often integrated into LOC systems to enhance detection sensitivity and specificity. For labeling and increasing signal intensity in biological assays gold nanoparticles, quantum dots and magnetic nanoparticles are employed. Nanofluidics -These optimized, nanoscale paths for fluids enable separate and identify specific materials such as DNA at a molecular level, providing excellent analysis.

Advantages of Lab-on-a-Chip

• LOC devices enable samples to be processed faster because the volume of fluids, and surface area to volume ratio is high.
• The miniaturization of laboratory processes leads to a reduced use of reagents as well as operating expenses
• They are compact in size, and this characteristic allows their application in the field for diagnostic and monitoring purposes
• LOC systems have the ability to carry out multiple operations of a laboratory at one time; hence, it is possible to have minimal interference from personnel
• LOC devices use less of biological and chemicals hence can be used for species that are hard to come by or are expensive to acquire.

Norchip AS – A device for carrying out cell lysis and nucleic acid extraction

The patent (EP2160243B1) addresses the challenges encountered in methods of analysing DNA and RNA and in particular those involving diagnostic, environmental and molecular biology. Normally, nucleic acid extraction and amplification (e.g., PCR) is done manually in laboratories which has been time-consuming and error-prone since it involves the use of laboratory technicians. The conventional method is slow, multistep (isolation, purification, amplification), and non-portable, thereby severely restricting its use at the point of care.

The proposed solution consists of an advanced Lab-on-a-chip patent that encompasses an automatic nucleic acid extraction system from the fluid sample. This device has provisions for the introduction of sample, cell disruption, nucleic acid collection and washing and employing a single pump with position valves that may be set at variable positions. The integration makes it faster, accurate that makes it fit for point of care such as clinical diagnosis or in-field diagnoses. The device also reduces the amount of reagents needed and the amount of sample needed to perform a given test, making it more cost effective.

Nanjing Lanyu Biological Technology Co Ltd – Closed micro-fluidic chip

The patent (CN212142656U) addresses the gap for an improved, reliable, and non-invasive technique for identifying Covid-19 and other viruses in an efficient microfluidic platform. The prospective conventional detection methods present risks of aerosol contamination, with augmented exposure and chance of viral dispersal to the testers. Moreover, the current approach is frequently less efficient and expensive since it involves several steps. There exist a number of requirements which should be met to create a microfluidic chip including the requirement of minimizing the risk of contamination, fast, reliable and easy to operate, and finally the requirement of low cost.

The solution presented in the patent is a closed micro-fluidic chip in which all components can be sealed to minimize the risk of leaks creating an aerosol during the detection process. It has sample injection cavity, reaction chambers, waste chamber all in one which is separated by microchannel. The additional structures within the system are the check valves which do not allow backflow effects in the system and a negative pressure traveling airbag which allows a safe containment of the sample. In this design the detection accuracy is high despite the fact that the whole design is cheaper to manufacture and easier to operate as compared to the previous designs. Because of its sealed setting, it is especially appropriate for virus detection in places such as clinics and laboratories.

Osmetech Technology Inc – Fluidics devices used in medical and diagnostic equipment

The patent (US7863035B2) refers to the difficulties during sample preparation for analysis as well as difficulties in detecting and quantifying target analytes present in liquid samples such as biological molecules. Current fluidic systems can erode mixing, creation of gas bubbles, and limitation of flow as a result the laminar nature of the fluids hamper its functionality in the diagnostic application. They also affect the analysis of small volumes of fluids typical used in laboratories, such as blood, serum and plasma, especially when it comes to measuring and filtering the fluids in diagnostics tests.

The patent introduces a fluidics device with integrated diaphragms and check valves for improved fluid control and sample processing. The design enables fine control over the flow of the fluid, reduces the formation of bubbles, and improves the vertexing of fluids within microchannels. The device comprises of several polymeric laminas with adhesive layers that define microchannels where the fluids have to pass through. It is optimized to works with small volumes of fluids and may contain detection chambers with immobilised biological recognition elements such as proteins or dna for the purpose of identification. This structure promotes the identification of target analytes in liquid biospecimens such as the well-known blood or urine samples enhancing the diagnostic accuracy and efficiency.

University of California – wireless power mechanisms for lab-on-a-chip devices.

The patent (US9484772B2) aims at solving the problem of supplying power and signal to lab-on-a-chip systems without the help of regular cable connections. In conventional setting, microfluidic systems use extra electrical mechanical equipment to produce AC and DC signals for the processes of cell sorting and detection among others. In addition to having potentially higher costs and larger footprints than internal devices, they also add layers of complexity to the user input/output process, and this can cause issues in testing and can also lead to errors, particularly where the classic characteristics of low cost, high simplicity, and high reliability are so important.

This patent offers an approach to this problem with a design of lab-on-a-chip integrated with a means for wireless power-transmission in the form of RF signals and light modulators to provide both AC and DC signals on the chip. The system therefore includes combined features for antennas and optoelectronic materials that are to transduce the received RF energy and light into electrical signals. This allows the device to do some basic operations such as heating, movement of cells and diagnosis without threading on any fixed electricity supply. DC to AC converters in the shape of photoconductive elements enable control of electrical environment within the chip which avails opportunities for procedures such as electrophoresis and dielectrophoretic for biological sample testing.