Sensor-Integrated Microfluidic Approaches for Liquid Biopsies Applications in Early Detection of Cancer

Abstract

Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies—the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment’s, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.

Perspectives on liquid biopsy for label‐free detection of “circulating tumor cells” through intelligent lab‐on‐chips

“…The integration of label‐free imaging, AI, and microfluidics is a subject of great interest in the scientific community to solve open biomedical questions 21,28‐31 . In particular, the authors of the present review strongly believe that such integration would represent a keystone for the identification of CTCs (Figure 1).…”

“…Indeed, many valuable papers describe the possibility to classify different cell types by combining QPI with AI in the field of tumor cell identification 16‐20 . In this framework, one of the main developing fields for the CTCs detection and isolation regards microfluidic engineering and its ingenious solutions able to perform both in marker‐based and label‐free systems 21‐27 …”

Biosensors-on-Chip: An Up-to-Date Review

“…Ever since their discovery, the detection of circulating tumor cells (CTCs) within liquid biopsies has attracted significant interest as a tool for early cancer diagnosis, metastatic cancer stage and cancer progression monitoring, and therapy response [ 92 , 93 ]. Microfluidic devices for CTCs analyses focus on cell isolation, detection, and examination, demonstrating a high efficiency, selectivity, and reactivity with reduced sample and reagent amounts and increased fluid control [ 71 , 92 ]. Most studies on the matter focus on isolating CTCs through immunoaffinity, which involves the immobilization of specific antibodies on the surface of the microchannels.…”

Biosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases

“…So far, biopsy samples are mainly blood and serve for the detection of tumor components including circulating tumor cells, circulating tumor DNA, cell-free RNA, extracellular vesicles, and miRNA. Unlike solid biopsies, liquid biopsy are less invasive and easier to obtain with the purpose of early disease detection (Sierra et al, 2020), prognosis and followup (Wan et al, 2017). Recently, attention has also been drawn toward oral fluid-based liquid biopsies for detecting RNA and miRNA in saliva and GCF.…”