Despite the many incredible advances in research, diagnosis and treatment, roughly 600,000 Americans will succumb to cancer this year, making it the second leading cause of death in the US behind heart disease.

It is well understood that early diagnosis significantly improves outcomes and for many years tumor biopsy has been the gold standard for diagnosing cancer patients. However, this technique – while highly effective - has plenty of downsides as well. In this article we will talk about the advantages of liquid biopsy and specifically how microfluidic “lab on a chip” technology takes it to the next level of sophistication and effectiveness.

Liquid biopsy requires sample preparation, amplification and target detection and this is what makes it well suited to being performed using microfluidic platforms. Microfluidic cartridges offer cellular separation and analysis that allows for high throughput with impressive sensitivity and specificity. By design, microfluidic channels carefully control liquid volumes and flow so sample size requirements are minimal and reagent use is low. This makes microfluidic cartridges well suited for separating and analyzing biomarkers for cancer diagnosis, treatment customization and ongoing monitoring.

Microfluidic technology is well suited for liquid biopsy because it facilitates the collection and isolation of very small quantities of CTC, ctDNA and Exosomes in blood. Disposable microfluidic “lab on a chip” cartridges. Microfluidic “lab on a chip” formats offer significant advantages for cancer biomarker detection.

CTC (Circulating Tumor Cells)

In the microfluidics world, cancer diagnosis is where the majority of research has focused for obvious reasons. Microfluidics opens up exciting possibilities in the liquid biopsy arena because of its ability to isolate circulating tumor cells which tend to be much larger than other blood cells. CTCs are important to understand due to the role they play in the metastatic process of cancer. Special channel geometries can be developed to isolate CTCs into different compartments, even going so far as to enable Single Cell Analysis (SCA). SCA can be used to analyze tumor composition and reveal insights into drug interactions within heterogeneous cell populations. One of the challenges is that our immune systems are designed to constantly attack CTCs and as such, few remain in peripheral blood. However, they do exist and microfluidic technology can be used to isolate and examine them.

ctDNA (Circulating Tumor DNA)

ctDNA comprises a small (0.1% to >10%) but important portion of
circulating DNA that is shed by tumor cells into the bloodstream and can be
detected in blood samples. It is a promising biomarker for cancer diagnosis,
prognosis, and monitoring of treatment response, as it reflects the genetic
changes occurring in the tumor and can provide insights into the underlying
molecular mechanisms driving the disease.

Microfluidic devices can be used to isolate and enrich ctDNA from a blood sample and perform sensitive and specific genetic analyses. This allows for the detection and quantification of specific genetic alterations, such as mutations or copy number changes, that may be indicative of cancer or other diseases. It also allows oncologists to identify residual disease and track mutations during therapy. Next Generation Sequencing (NGS) can generate even more information useful for analyzing the tumor.

Exosomes

Exosomes are small vesicles (30-150 nm in diameter) that are secreted by cells and can be found in body fluids, such as blood and urine. They contain various biomolecules, including proteins, nucleic acids, and lipids, and are thought to play important roles in cell-to-cell communication, immune regulation, and the transfer of genetic information.

In the context of cancer, exosomes have been shown to carry tumor-derived genetic and epigenetic information that correlates well with immune response suppression, angiogenesis, tumor progression and metastasis. Exosomes can be used as biomarkers for cancer diagnosis, prognosis, and monitoring of treatment response and are particularly attractive for diagnosis because they are stable, easily detected in body fluids, and tend to increase substantially in cancer patients. Exosome analyses can also be used to complement ctDNA and CTC biodata.

Because exosomes are present in all bodily fluids, they are ideally suited for microfluidic Point of Care (POC) tests. Microfluidic devices can be used to isolate and enrich exosomes from blood, urine and saliva and perform sensitive and specific analyses, such as western blotting, PCR, or NGS. These techniques allow for the detection and quantification of specific biomolecules, such as proteins, nucleic acids, or lipids, that may be indicative of cancer or other diseases. Challenges remain in efficiently isolating exosomes for further molecular analysis due to overlapping sizes of exosomes.

Blood-based liquid biopsy is not new. Several biomarker tests have been developed including those used to detect prostate, colon, pancreatic and ovarian cancers. While liquid biopsy continues to improve in accuracy, it will still be some time before blood-based biopsies are trusted as much as tissue-based techniques in use for decades. The primary reason is that diagnosis is challenging due to the fact that cancers often have high tumor heterogeneity which is also representative in the biomarkers. Nonetheless, microfluidic technology has the ability to solve this issue and change perceptions, improving accuracy and specificity of results and significantly altering the workflow for cancer therapy. Cancer diagnosis and treatment processes in the future may involve a patients getting simple blood draws during the diagnosis, treatment and monitoring phases with less reliance on imaging and tumor biopsies. Microfluidic technology may drive that transformation for the betterment of all involved.