Advances in liquid biopsy on-chip for cancer management: Technologies, biomarkers, and clinical analysis

Abstract

Liquid biopsy, as a minimally invasive method of gleaning insight into the dynamics of diseases through a patient fluid sample, has been growing in popularity for cancer diagnosis, prognosis, and monitoring. While many technologies have been developed and validated in research laboratories, there has also been a push to expand these technologies into other clinical settings and as point of-care devices. In this review we discuss and evaluate microchip-based technologies for circulating tumor cell (CTC), exosome, and circulating tumor nucleic acid (ctNA) capture, detection, and analysis. Such integrated systems streamline otherwise multiple-step, manual operations to get a sample-to-answer quantitation. In addition, analysis of disease biomarkers is suited to point of care settings because of ease of use, low consumption of sample and reagents, and high throughput. We also cover the basics of biomarkers and their detection in biological fluid samples suitable for liquid biopsy on-chip. We focus on emerging technologies that process a small patient sample with high spatial-temporal resolution and derive clinically meaningful results through on-chip biomarker sensing and downstream molecular analysis in a simple workflow. This critical review is meant as a resource for those interested in developing technologies for capture, detection, and analysis platforms for liquid biopsy in a variety of settings.

The Innovations, Advances and Outlooks of Liquid Biopsy in Oncology: A Literature Review

“…Biosensors are small devices that use tumor biomarkers as recognition elements or analytes, and are linked to a system of detection, transduction and amplification of the signal generated in the reaction with the target analyte, being in the oncology to detect the characteristics of tumors, as well as obtaining valuable clinical information that can guide treatment. 5 CTCs, for example, are enumerated from the CellSearch ™ platform, which is the only one authorized by the FDA. 2 It is crucial that these techniques are studied and developed in order to increase analytical sensitivity.…”

“…There are several biomarkers used in liquid biopsies, such as circulating tumor cells, free-cell DNA, tumor cell DNA and exosomes. [2][3][4][5]7,8,10,11,[12][13][14][15][16][17][18][19][20] The choice of biomarkers for early detection of cancer is crucial, but it is important to note that they may have high sensitivity and specificity. 4…”

“…Advances in the understanding of molecular biology of cancer have led to the development of the Liquid Biopsy, which is a revolutionary new and reproducible technique, serving for the early detection of malignant neoplasms, as well as for the initiation of personalized and precise treatment, analysis of treatment response in real time, in addition to the prognosis of patients. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This tool is currently called the Net Biopsy and uses the detection of biomarkers of cancer cells, such as circulating tumor cells (CTCs), circulating cell DNA (cfDNA), DNA of tumor cells (ctDNA) and exosomes, which can be detected in various fluids, such as blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF) . [2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This tool is currently called the Net Biopsy and uses the detection of biomarkers of cancer cells, such as circulating tumor cells (CTCs), circulating cell DNA (cfDNA), DNA of tumor cells (ctDNA) and exosomes, which can be detected in various fluids, such as blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF) . [2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies. [1][2][3][4]6,7,[10][11][12][13][14][15][16][17][18][19][20] This new technology can develop a new concept of individualized or personalized therapy...…”

“…[1][2][3][4]6,7,[10][11][12][13][14][15][16][17][18][19][20] This new technology can develop a new concept of individualized or personalized therapy, favoring an understanding that the same type of cancer and in the same stage of disease may have different treatments in different patients, because the liquid biopsy may also verify the heterogeneity and some types of tumor mutations and resistance to some types of drugs used in chemotherapy. 2,4,5,8,9,17 This approach, however, requires the development of reliable biomarkers and biosensors. 2,4 Conventional biopsies are often invasive, sometimes impractical and many others technically challenging, while liquid biopsies can be performed serially.…”