Modern medicine has been able to drastically improve the quality of life of the global population. Diseases such as polio, syphilis, tuberculosis or the plague have been almost eradicated and are successfully treatable or curable. The next milestone for modern medicine is personalized medicine. This novel discipline does not target the broad population, but focuses on the individual for the diagnosis and beyond. Personalized medicine takes the individual’s disease pattern, the patient’s constitution and gender and the resulting implications for the therapies and medicines into account. The overall goal is to create a therapy tailored to the individual that can, if necessary, be adjusted and fine-tuned according to the disease progression.

The combination of a plethora of modern technologies is required to enable such specialized treatments. As such, a tailored cancer therapy could be designed using flow cytometers, DNA sequencing and organ-on-a-chip applications.

Flow cytometers are used for high throughput cell analysis. In these devices, cells flow past an analysis unit (e.g. voltage or fluorescence read-out) at high velocity. The recorded voltage or light signal depends on the shape, structure, size and/or color of the cells. This way, cells with the desired properties can be identified and isolated using cell sorter technology.

Flow cytometers have received special attention with regard to circulating tumor cells (CTCs) in the blood of cancer patients. CTCs can be isolated from the patients’ blood and can therefore be a minimally invasive alternative to potentially complex and invasive traditional biopsies. These liquid biopsies have the potential to reduce the patients’ pain level, the overall risk and the total costs. In cases where the position of the primary tumor or the patient’s constitution does not allow for a traditional procedure, the CTCs can be used to gather the critical data required for a complete diagnosis.

CTCs, which were found in a cancer patient’s blood for the first time in 1869, typically originate from the primary tumor and are leaked into the blood stream or the lymphatic system. CTCs can be found in a blood sample even at early stages of the disease. At 1-10 CTCs per mL whole blood compared to millions of white and billions of red blood cells, their concentration is extremely low and highly sensitive flow cytometers and cell sorters are required to detect and isolate them.

Following detection and isolation of the CTCs, the next step is the characterization. This characterization can and must go down to the molecular level and even the DNA of a single tumor cell can be sequenced. Next Generation Sequencing (NGS) is used to generate the data reliably and quickly.

NGS is able to record the nucleotide sequence of DNA with significantly increased throughput compared to traditional sequencing methods such as Sanger sequencing. The DNA sequence can yield information about the type of tumor, the CTC-specific mutations and thus enable a specific prognosis on disease progression and help in therapy design. Combining NGS and CTCs can therefore be a viable alternative to traditional invasive biopsies.

In medical diagnostics, the trend towards near-patient lab diagnostics (point-of-care testing, or POCT) continues apace. The idea is that testing should take place as promptly as possible and ideally directly at the patient’s bedside. For more complex examinations, precise microfluidic systems are required.

One well-known example of a POCT is a urine test using a paper strip. In these tests, the different components of urine – such as red and white blood cells, glucose and the pH value – cause color changes on the reactive surfaces of the test strip. By comparing of the color patterns to a reference scale, the nurse can ascertain qualitative information about the concentration of the various substances in the sampled urine. In an even simpler exemplary procedure, the oxygen saturation of blood can be determined non-invasively through the skin by clipping an optical sensor to the fingertip of the patient. Previously, before the advent of these pulse oximeters, a blood sample had to be taken and sent to the central lab for testing.

More complex tests – for example, to detect certain viruses or bacteria – still depend on the elaborate infrastructure and specialist personnel of a central lab. Such tests often require additional steps in terms of sample preparation or pre-treatment, special temperature conditions or complex devices for analysis. In order to carry out these tests directly at the patients’ bedside in the hospital, the test procedures must be simplified and interaction with the user minimized. In ideal cases, the entire test is conducted independently on a single microfluidic system; i.e. the entire ‘lab’ is integrated on a chip and thus becomes a ‘lab on a chip’.

In recent decades, a great deal of research has been carried out in the field of microfluidics, particularly in the biosciences, with the aim of miniaturizing and automating lab experiments, diagnostic tests and (bio)chemical processes. Instead of pipetting discrete quantities of liquids from one container to another, today the liquid in a microfluidic system flows through the tiny channels of a manifold. The liquid in these channels is generally moved by external pumps or pressure sources to which the fluidic chip is connected. To control the applied pressures or stabilize the flow generated by the pump, the flow rate is measured using flow sensors. Thanks to their outstanding sensitivity even at extremely minimal flow rates, Sensirion’s microthermal mass flow meters for liquids set the industry standard in the precise monitoring of liquid flows in microfluidic systems.

The dimensions of the channels in the fluidic system have been significantly reduced down to the micrometer range, with the liquid volumes in the microliter or even nanoliter range. This enables the microfluidics to drastically reduce the sample and reagent quantities, enable faster reactions and thus increase throughput. And the smaller size of the fluidic system also means lower costs and smaller devices. Both are necessary conditions in order to conduct tests in a decentralized manner directly at the place of care; i.e. at the bedside, on the same hospital floor or in a doctor’s office. This, in turn, simplifies the logistics and provides faster results for better and more targeted treatment of patients.

Commercially available microfluidic POCT devices can be used, for example, to measure proteins used as biomarkers in the diagnosis of heart attacks. Other devices analyze blood samples to determine the composition of red and white blood cells, and their subtypes. Another application in medical technology is cytometry to determine the concentration of T helper cells in monitoring the immune systems of HIV/AIDS patients. Finally, efforts are also under way to transfer molecular-biological methods for the detection of, for example, antibiotic resistant bacteria via their DNA to point-of-care systems. Even genetic fingerprints for forensic purposes can be created using POCT devices.

However, microfluidics play an increasingly important role in areas other than the clinical field, such as research and development and industrial process monitoring. In particular, microbiology is absolutely critical today in the food and drinks production sector; it is used to monitor the quality of yeast cells that ferment malt to beer, and the bacterial populations in milk, which must not exceed certain threshold values. Hitherto, discrete samples have been diverted from the production process and sent to laboratories for testing; now new types of miniaturized flow cytometers enable direct verification of individual production lots or even continuous monitoring on the production line.