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== Problem == '''Cancer still is a major global health issue''' According to the International Agency for Research on Cancer (IARC), in 2020, the number of new registered cases surpassed 19.2 M globally, whereas over 9.9 M deaths were attributed to this disease [1]. Despite all the recent breakthroughs in cancer treatments, it is estimated that by 2040, the number of new registered cases and fatalities per year will increase to 30.2 M and 16.3 M, respectively [2, 3]. '''One of the main reasons cancer still has such a high mortality rate is due to the current lack of tests with the required sensitivity and specificity to aid in the early diagnosis of the disease.''' [[File:F82b6b4eb997f1f74e0fc2579715da887b94634d.png]] '''When it comes to cancer, the detection of tumors at an early stage is key because the survival rate in most types of cancer is directly related to the stage at which tumors are detected.''' For example, the 5-year relative survival rate for breast cancer when detected at an early stage is 99%, but drops to 28% when detected at a late stage [4]. Furthermore, early detection has the potential of reducing the financial burden of health care on individuals and public health services mainly because cancer treatments used for treating localized disease are less complex, and therefore, less expensive; according to the World Health Organization (WHO), studies made in high-income countries have shown that the cost of cancer treatment, when detected at early stages, is 2 to 4 times less expensive than at advanced stages [5]. Moreover, there is also a lack of technological resources to provide effective monitoring of the applied cancer treatments’ efficacy, which may significantly reduce the patients’ chances of survival given that the right treatment at the right time for each cancer patient may not be administered due to the lack of information available for physicians. Since there is an unmet need for tests that can reliably detect cancer at early stages and monitor the applied treatments’ effectiveness, the research community has been actively searching for novel biomarkers that can provide clinical information for these purposes. The isolation of circulating tumor cells (CTCs) from blood is a recent alternative that could address this need. '''In the last decade, CTCs have attracted a significant amount of attention for their potential use as a blood-based biomarker for a broad range of cancer-related clinical applications.''' CTCs are malignant cells that are shed from the primary and/or metastatic solid tumors and then infiltrate into the vascular and lymphatic systems; these cells play a fundamental role in the metastatic process of non-hematological cancers [6, 7]. Technologies that detect and isolate CTCs from blood can be used to develop assays that could enable early cancer detection and monitor the applied treatments’ effectiveness. '''However, the isolation of these malignant cells from blood represents a major technological challenge due to their heterogeneity and extremely low numbers in comparison to blood cells''' [8, 9]; on average you can find around 40.5 billion cells in 7.5 mL of blood, while a cancer patient may have between 1 and 1000 CTCs in the same volume [10]. Even though there currently exists multiple cell sorting methods, such as fluorescent-activated cell sorting, magnetic-activated cell sorting, fluorescent-activated droplet sorting, and density gradient centrifugation, these are not compatible with whole blood samples and/or do not have the sufficient sensitivity and specificity to correctly isolate CTCs from blood, which have prevented the development of assays with potential clinical utility... until now.
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