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 cytometer for analysis and diagnosis
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.
DNA sequencing and characterization
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.