Unveiling the Mystery of Liquid Biopsy Technology

Liquid biopsy?is?an emerging tumor diagnostic technology. Compared with traditional detection methods, it has the advantages of less trauma, convenient sampling, and real-time dynamic detection. It plays an important role in early tumor screening, molecular typing, recurrence monitoring, and prognosis evaluation.

Compared with traditional tissue biopsy, liquid biopsy technology can obtain information about disease states such as tumors, infectious pathogens, genetic mutations, etc. through biomarkers in body fluid samples (such as blood, urine, cerebrospinal fluid, etc.).

Soluble molecules such as DNA, RNA and proteins released by tumor cells can spread to other parts through the blood circulation system, forming so-called circulating tumor markers. By analyzing circulating tumor markers in the blood, it is possible to detect the presence of tumors, assess their progression and treatment response, and even make individualized treatment decisions.

Currently, the biomarkers of liquid biopsy are mainly tumor cell-derived entities, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and Exosome.

Commonly used liquid biopsy techniques include:

1 Circulating Tumor DNA?(ctDNA):

Detect and analyze genetic mutations of tumors by analyzing DNA fragments released by tumor cells in the blood.

ctDNA is a tumor DNA fragment that exists in human blood. When tumor cells proliferate, some cells die or are destroyed, releasing tumor cell DNA fragments. These DNA fragments can enter the circulatory system and be transported to other parts of the body through the blood.

The characteristic of ctDNA is that it contains information about mutations and variations from tumor cells. These mutations and variations are present in tumor cells, so their detection can provide key information about the tumor, such as its presence, size, stage, and response to treatment.

ctDNA analysis can be used for early detection of tumors, monitoring tumor progression and treatment response, assessing patient prognosis, and discovering drug-resistant mutations.

ctDNA is rare in whole blood, approximately 1-30 ng/mL. It requires multiple pre-processing steps, including plasma separation, DNA processing and purification.

2 Circulating Tumor Cells (CTCs):

Used to detect the presence and number of circulating tumor cells in the blood or other body fluids. Circulating tumor cells are malignant tumor cells that have shed from the primary tumor and entered the circulatory system. They can be transported to other parts of the body through the blood.

There are many methods for CTC detection, and common technologies include:

Immunomagnetic Separation: Circulating tumor cells are separated from other cells using specific antibodies or markers, and then observed and counted by microscopy or flow cytometry.

Label-Free Cell Capture: Circulating tumor cells are captured and enriched through microstructures or surface modification materials using technologies such as microfluidic chips or microwell arrays.

Polymerase Chain Reaction (PCR): Use specific gene mutations or gene expression markers to amplify and detect DNA or RNA in circulating tumor cells.

Fluorescence In Situ Hybridization (FISH): Use fluorescent probes to label specific chromosomal deletions, rearrangements, or mutations and observe circulating tumors under a microscope.

3 Exosomes are a type of extracellular vesicles.

They were initially thought to be waste cell secretions, but with the deepening of research, people gradually realized that they play an important role in transmitting information between cells and regulating cell function.

Exosomes are mainly composed of cell membrane-enclosed vesicles with a diameter of about 30 to 150 nm. They are produced by various types of cells, including multiple cell types such as tumor cells, immune cells, nerve cells, and hematopoietic cells. Exosomes contain a variety of bioactive molecules, such as proteins, nucleic acids, lipids, and cytokines.

Exosomes achieve intercellular communication by contacting target cells or releasing their contents. They can enter different tissues and organs in the body through body fluids such as blood, urine, saliva, and milk, thereby affecting the function and behavior of target cells. In this way, exosomes participate in a variety of physiological and pathological processes, including cell growth, immune regulation, angiogenesis, tumor metastasis, etc.

Reference:

Microfluidic systems for cancer diagnostics.