Lab-on-a-Chip: Mega analyses in micro spaces

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A lab-on-a-chip (LoC) is a microfluidic analysis system that combines various laboratory diagnostics methods on a single component that is roughly the size of a credit card. An LoC system – also called micro total analysis system (μTAS) or biological microelectromechanical system (BioMEMS) – combines microelectronics and microfluidics. Capillary forces transport the samples that are to be investigated in micro-channels from one reaction or analysis chamber to the next.

The diameter of these channels can be as small as 50 micrometers – 0.05 millimeters. Extensive biological, chemical, and physical processes take place in the tiny chip lab. Integrated sensors enable many different parameters to be monitored precisely. For example, biological interactions down to cell and molecular levels can be observed.

Market research company Stratistics MRC predicts that the global market for lab-on-a-chip systems will grow by about 11 percent per annum and reach a volume of approximately USD 7.95 billion by 2022. North America has the largest market share because of its increasing aging population. The LoC market is growing fastest in the Asia-Pacific region – especially in China and India – and in Europe.

Faster, better, cheaper

The miniature laboratories perform analyses much faster than conventional labs and they can also carry out hundreds of tests at the same time. LoCs are more compact, more portable, and more energy-saving than conventional analysis equipment and can be produced in large numbers inexpensively using 3D printing methods. Only tiny sample volumes are needed for fully automated analysis, such as a drop of blood, saliva, or sweat. Reagent consumption is also minimal. Patients benefit from a fast and precise in-situ diagnosis and can receive carefully targeted treatment. This reduces the costs of treatment.

Microanalysis systems have the potential to change diagnostic processes. More widespread use could see a shift in services in the healthcare system: in the future, tests that are now carried out in laboratories or specialist surgeries could potentially be conducted by GPs or the patients themselves.

Enormous potential for point-of-care testing

These miniature labs can be used in medical engineering, biotechnology, chemistry, cell biology and even in the pharmaceutical industry. LoCs are also becoming increasingly relevant in individualized medicine, point-of-care testing (POCT), and in-vitro diagnostics.

Physicians use LoC tests for in-situ diagnosis, such as rapid blood tests, rheumatism diagnostics, and biomarker emergency test strips in cases of heart attack. In the clinical area, LoC applications have potential in infection diagnostics – such as bacterial and viral infections. Some LoCs can even be used by people with no medical training (direct-to-consumer, DTC) such as in personalized drug therapy. In Germany, there are about 20 drugs for which a companion diagnostic test is obligatory. On the other hand, genetic self-testing and HIV self-testing are banned in Germany.

The mini laboratories are also interesting for drug development, which requires high-level parallelization, and in biotechnology, for example, in the biotransformation of molecules with enzymes, bacteria or cell cultures to antibiotics, insulin, or steroids. LoC systems are also expected to have potential for global healthcare. Public health applications include tests for multiple drug resistant tuberculosis pathogens and self-tests during pandemics like influenza.

Personalized chemotherapy against cancer

Conventional chemotherapy often does not work against cancer as human tumor cells respond to drugs in very different ways. Bernhard Wolf, head of the Steinbeis Transfer Center for medical electronics and lab-on-chip systems, developed a test method that will determine a drug matrix tailored to the individual person and the optimum dosage.

The lab-on-a-chip consists of a microtiter plate with 24 reaction chambers each of which contains a multi-parameter sensor. Patients’ tumor tissue samples are cultivated directly on these sensors. In the Intelligent Microplate Reader (IMR), a pipetting robot fills therapeutic agents with different combinations and concentrations into the 24 reaction chambers. The sensors record changes in the oxygen concentration, the pH, and electrical conductivity. The integrated fluidics provide almost in-vivo conditions.

Wolf explains: “The special feature of the system is that it tests metabolic patterns.” When the oxygen consumption of the tumor cells decreases once they come into contact with an active ingredient, in other words, when they stop metabolizing, this could be an indication that the drug is effective for the patient. In a clinical trial, it will be checked whether the test system can actually predict the patient’s response to treatment correctly. In the future, the system could be used generally to test drugs and replace experiments on animals.

Drug development with multi-organ chips

There is worldwide demand for new drugs. However, clinical trials are time-consuming and expensive. This is why new active ingredients are first tested on animals, although the results cannot simply be transferred to humans. These trials are also controversial from ethical aspects. Therefore, the Karlsruhe Institute of Technology (KIT) has developed an organ-on-a-chip system with accurately modeled blood vessels. The KIT spin-off vasQlab developed the chip lab further.

Three-dimensional mini organs made from human cells are applied to the vasQchip with a 3D printer. The active ingredients to be tested are directed to the mini organs via artificial blood vessels. A miniature pump simulates the heart. This allows the effects and compatibility of an active ingredient to be investigated in a pre-clinical phase without any experiments on animals.

The mini-organ chip will enable thousands of tests to be conducted automatically at the same time – in a very small space. vasQlab is currently developing skin, liver, bowel, and brain models and a combination of various miniaturized organs on one chip. “We want to offer the pharmaceutical and cosmetic industries better alternatives to animal tests that offer more precise prognosis of the effect on humans and that are also less expensive,” explains Vanessa Kappings from KIT.

Rapid tests for multiple drug resistant germs

Multiple drug resistant germs are a growing threat. Standard methods for infection diagnostics require up to 72 hours before a result is available. However, in the treatment of serious infections – such as septicemia – time is of the essence. Intensive care physicians face a dilemma: “In many cases we have to treat patients with broad-spectrum antibiotics, as we are initially unable to determine the pathogen or any potential resistances. We’re more or less using a sledgehammer to crack a nut,” explains Michael Bauer from Jena University Hospital in Germany.

An innovative rapid test can now, within three and a half hours, provide information as to which antibiotic could be effective. It was developed at the Leibniz Institute of Photonic Technology (Leibniz-IPHT), Jena University Hospital, and the University of Jena. “The lab-on-a-chip system combines light-based analysis methods with microfluidic sample processing. This allows us to quickly and clearly identify bacterial strains and their resistances,” says project manager Ute Neugebauer.

Electric fields secure bacteria on the postage stamp-sized chip. The pathogens are brought into contact with different antibiotics in various concentrations and are investigated using Raman spectroscopy. The scientists irradiate the pathogens with laser light and evaluate the scattered light spectrum. From the results it is possible to see whether a strain is resistant or sensitive and how high the concentration of antibiotic must be. The method could improve diagnosis of contagious diseases and stem antibiotic resistance.

Nanotechnology and energy supply

At present, relatively few lab-on-a-chip systems are approved for clinical applications. Many projects are still in the development phase. In the future, advances in nanotechnology will expand the potential applications for LoC systems. In microsystem technology, the energy supply for LoC units is one of the main research areas.

electronica 2018

Microsystem technology diagnostics (lab-on-a-chip) is a focal point at the electronica Medical Electronics Conference. At the world’s leading trade show for electronics, around 100 international exhibitors will present their products and solutions in the field of micro and nano Systems.

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