DNA Nanospheres with Microfluidics: A Promising Platform for Cancer Diagnosis?

Abstract

The mortality rate from cancer in the USA reached more than 570,000 in 2012, or equal to more than 1500 Americans each day [1]. More than 90% of cancer deaths result from metastasis [2], hence methods for early-stage cancer detection are vital for the reduction of mortality and they will have a significant medical and social impact. However, according to the Early Detection Research Network of the National Cancer Institute, ‘there are no validated molecular biomarker tests for the early detection of any cancer’ [3], even though a handful of biomarkers have been approved by the US FDA. It is known that, during metastasis, some cancer cells escape from the primary tumor through exfoliation, entering the bloodstream and becoming circulating tumor cells (CTCs) in the peripheral blood stream [2,4]. Some of these CTCs acquire the capability to colonize secondary sites, spreading tumors to distant organs [2,4]. Therefore, CTCs have the potential to serve as important biomarkers for early diagnosis of cancer metastasis [2,4]. An additional benefit is that CTC enumeration is less invasive than biopsy, while providing a quantifiable method for cancer diagnosis and prognosis. However, CTCs are extremely rare; the number of CTCs is in the order of one to 100 cells in 1 ml of blood [4]. For comparison, other cells in 1 ml of blood include approximately 5 × 10 erythrocytes, 7.8 × 10 leukocytes and approximately 3.5 × 10 platelets [5]. Therefore, detection of CTCs in peripheral blood is a needlein-a-haystack challenge. Currently, CellSearch (Veridex LLC, NJ, USA) is the only FDAapproved method, and it relies on antibodycoated magnetic particles for isolation of CTCs from blood [4]. One of its key drawbacks is low capture efficiency. Microfluidics could play an important role in enhancing the capture efficiency of CTCs.