from circulating biomarkers (CBs). CBs may be found in several minimally invasive bodily fluids including (but not limited to) blood, saliva, urine, pleural effusions, stool, and cerebrospinal fluid. CBs may include circulating tumor cells (CTCs), circulating tumor RNA/DNA (ctRNA/ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins, exosomes, autoantibodies, all of which, are known for their diagnostic and prognostic potential. [1] Currently, clinicians and centralized hospitals practice tissue biopsy for diagnosis and characterization of the heterogeneity of the solid tumor which is crucial for personalized medicine. [1a] Despite the many decades of clinical practice, tissue-based biopsies are subject to sampling bias, suffer from the issue of low repeatability, and cause immense pain in patients as the process is invasive. One of the major concerns of biopsies, often ignored, is the entrance of tumor cells into the systemic circulation during the tissue-sampling process, leading to tumor metastasis. [2] To overcome these issues, the detection of CBs through liquid biopsy has shown promise as a potential replacement due to the rapid and semi or non-invasive sampling process and the repeated analysis of samples during therapeutic interventions aid in decision-making about a particular patient's progress.Due to the advancement of highly specific sequencing and gene amplification technologies, liquid biopsies can access more relevant cancer biomarkers, providing a much-needed alternative to tissue-based biopsy. [1b] These recent advances have led to the development of many miniaturized/ portable platforms. The clinical potential of these micro and nano devices is rapidly growing, but they face many challenges before transitioning to point-of-care (POC) platforms that are sensitive, rapid, and accurate, as discussed herein.Previously, our group [3] provided a critical review of circulating tumor DNA (ctDNA) and liquid biopsy opportunities, challenges, and recent advances in detection technologies. The review examines the potential of ctDNA as a marker in liquid biopsy, as well as the detection methods, challenges, and considerations. We further [1b] provided a comprehensive review of advanced liquid biopsy technologies for CBs detection. Others Liquid biopsy for the analysis of circulating cancer biomarkers (CBs) is a major advancement toward the early detection of cancer. In comparison to tissue biopsy techniques, liquid biopsy is relatively painless, offering multiple sampling opportunities across easily accessible bodily fluids such as blood, urine, and saliva. Liquid biopsy is also relatively inexpensive and simple, avoiding the requirement for specialized laboratory equipment or trained medical staff. Major advances in the field of liquid biopsy are attributed largely to developments in nanotechnology and microfabrication that enables the creation of highly precise chip-based platforms. These devices can overcome detection limitations of an individual biomarker by detecting multiple markers ...