Exploring the Use of Liquid Biopsy–Based Biosensors for MRD Assessment in NSCLC

In a recent study, researchers detailed the use of various biosensors for minimal residual disease (MRD) detection in non–small cell lung cancer (NSCLC).

As uptake of liquid biopsy for detecting and monitoring minimal residual disease (MRD) in non–small cell lung cancer (NSCLC) continues, researchers have compiled data on the use of liquid biopsy–based biosensors for MRD monitoring in these patients. Their review was published in the journal Biosensors.

Considered ultrasensitive, biosensor-based methods for liquid biopsy are comprised of 3 parts: the bioreceptor to collect the substance, the transducer that transforms the substance into a distinct signal, and the biosensor analyzer that shows the results.

“Biosensor-based test for liquid biopsy MRD and treatment monitoring has shown bright horizons in NSCLC. A lower concentration of [circulating tumor] DNA and [circulating tumor cells] in body fluids can be detected by a biosensor,” explained the researchers. “The widespread use of biosensors in MRD diagnosis reduces costs and expands the availability of these tests to monitor treatment or choose adjuvant immunotherapy in early stages of patients.”

Electrochemical sensors are those that convert the biochemical interaction to electrical signals. In the context of MRD assessment in NSCLC, these sensors, which can be used in real time, are considered ideal for personalized medicine because they are easily miniaturized. Their electrochemical aptasensors can be reused, although they are less sensitive than other electrochemical methods, and the researchers note that false results are possible due to nonspecific binding.

Magnetic biosensors apply paramagnetic particles to detect biological interactions and are able to detect multiple biomarkers simultaneously, often being used as an immunoassay-based liquid biopsy, DNA-based liquid biopsy, or point-of-care devices. These biosensors have high sensitivity but are costly and time consuming.

Surface-enhanced Raman spectroscopy uses molecules absorbing on rough metal surfaces to generate Raman scattering. These sensors offer real-time monitoring of therapy response, have high sensitivity, and have high spatial resolution. They also have a complex structure, are time consuming and expensive, and require a trained technician.

Surface plasmon resonance biosensors alter the surface plasmon resonance angle by increasing the refractive index during the binding of molecules on the sensor surface. Used for monitoring immune checkpoint inhibitors (ICIs), these biosensors have high photostability and high sensitivity but require a trained technician, are costly, and have sample losses during the labeling and purification process.

Fluorescence-based biosensing involves an analytical signal of a photoluminescence emission mechanism and is used for the monitoring of ICIs, including PD-L1 inhibitors. Compared with other optical methods, fluorescence-based biosensing is preferred for detecting MRD because of its high sensitivity, reliability, and reproducibility. The method requires a trained technician and is costly.

Lateral flow immunoassay has optical properties and its test strips are used for detecting extracellular vesicles and, according to the researchers, may have potential for being a quantitative test. These biosensors are rapid, portable, user-friendly, and cost-effective but have low sensitivity.

Chemiluminescence is based on electrochemistry and visual luminescence measurements, which required a shorter DNA region. These tests are simple, have high sensitivity, and a broad dynamic range but have reagent low stability and are time consuming.

The authors concluded that they expect the accuracy and reliability of MRD detection tests to improve even further in the next decade.


Sardarabadi P, Kojabad A, Jafari D, Liu C. Liquid biopsy-based biosensors for MRD detection and treatment monitoring in non-small cell lung cancer (NSCLC). Biosensors (Basel). 2021;11(10):394. doi:10.3390/bios11100394

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