Recent advances for cancer detection and treatment by microfluidic technology, review and update

Abstract

Numerous cancer-associated deaths are owing to a lack of effective diagnostic and therapeutic approaches. Microfluidic systems for analyzing a low volume of samples offer a precise, quick, and user-friendly technique for cancer diagnosis and treatment. Microfluidic devices can detect many cancer-diagnostic factors from biological fluids and also generate appropriate nanoparticles for drug delivery. Thus, microfluidics may be valuable in the cancer field due to its high sensitivity, high throughput, and low cost. In the present article, we aim to review recent achievements in the application of microfluidic systems for the diagnosis and treatment of various cancers. Although microfluidic platforms are not yet used in the clinic, they are expected to become the main technology for cancer diagnosis and treatment. Microfluidic systems are proving to be more sensitive and accurate for the detection of cancer biomarkers and therapeutic strategies than common assays. Microfluidic lab-on-a-chip platforms have shown remarkable potential in the designing of novel procedures for cancer detection, therapy, and disease follow-up as well as the development of new drug delivery systems for cancer treatment.

Keywords: Laminar flow; Metastasis; Microfluidic; Tumour.

Fig. 1

A schematic image of aptamer-based CTC capture and detection processes: (a) Sample injection; (b) CTCs trapping and FET sensing

Fig. 2

A hypothetical Cas13-based microfluidic biosensor for cancer diagnosis. First, the blood of NSCLC patients, containing materials derived from the tumor, enters directly into the entry well. After the isolation of the nucleic acids, they are followed into wells containing reagents for the detection of DNA mutations or quantifying overexpressed NSCLC-associated RNAs. Cas13 is activated by direct targeting of RNAs and subsequent matching of the target RNA sequence with the crRNA spacer sequences. This leads to cleavage of the target RNA and fluorescent reporter RNAs. On the other hand, after amplification of tumor DNAs with RPA, the T7 promoter sequence is added to the 5'-end of the RPA forward primer, and RPA amplicons are transcribed with T7. By binding to mutation-containing transcripts, Cas13 cleaves fluorescent reporter RNAs to provide the detectable signals

Fig. 3

Biomimetic tumour-induced angiogenesis in a microfluidic device. The angiogenesis unit is depicted in this diagram, which has one open cell culture chamber and two channels of angiogenesis. The steps of cell loading are depicted in the diagram

Fig. 4

Modelling systemic metastasis in a body-on-chip An illustration is provided to represent the metastatic progression in the future using a human body-on-chip consisting of multiple fluidically connected organs-on-chips, which are often referred to as organ chips, such as the liver, brain, lung, and bone chips. On this body-on-chip, arrows indicate blood circulation, showing lung cancer cells growing on a lung cancer chip invading the vascular channel. Then cancer cells spread to the other chips, owing to fluid connections and pumping of the same medium to multiple chips. This is similar to how blood is pumped from the heart to every other organ in the body. The progression of metastatic lesions could be monitored by observing lung cancer cells with fluorescent markers penetrating the circulation of fluid. These markers could be inserted into the liver, bone, or brain chips from afar. Metastasizing lesions typically occur at these sites where studies could be conducted to identify and study the growth of metastatic cancer cells. By using this method, it would be possible to determine the mechanisms by which tumour cells attack particular organs (organotropism) and also recognize possible pharmacological approaches to inhibit metastatic cancer cells spread