On Demand Biosensors for Early Diagnosis of Cancer and Immune Checkpoints Blockade Therapy Monitoring from Liquid Biopsy

Abstract

Recently, considerable interest has emerged in the development of biosensors to detect biomarkers and immune checkpoints to identify and measure cancer through liquid biopsies. The detection of cancer biomarkers from a small volume of blood is relatively fast compared to the gold standard of tissue biopsies. Traditional immuno-histochemistry (IHC) requires tissue samples obtained using invasive procedures and specific expertise as well as sophisticated instruments. Furthermore, the turnaround for IHC assays is usually several days. To overcome these challenges, on-demand biosensor-based assays were developed to provide more immediate prognostic information for clinicians. Novel rapid, highly precise, and sensitive approaches have been under investigation using physical and biochemical methods to sense biomarkers. Additionally, interest in understanding immune checkpoints has facilitated the rapid detection of cancer prognosis from liquid biopsies. Typically, these devices combine various classes of detectors with digital outputs for the measurement of soluble cancer or immune checkpoint (IC) markers from liquid biopsy samples. These sensor devices have two key advantages: (a) a small volume of blood drawn from the patient is sufficient for analysis, and (b) it could aid physicians in quickly selecting and deciding the appropriate therapy regime for the patients (e.g., immune checkpoint blockade (ICB) therapy). In this review, we will provide updates on potential cancer markers, various biosensors in cancer diagnosis, and the corresponding limits of detection, while focusing on biosensor development for IC marker detection.

Investigating the Changing Levels of Immune Checkpoint Proteins in The Serum of Breast Cancer Patients

“…Therefore, immunological checkpoints may struggle to identify cancer owing to TIM-3 expression variability. In addition, TIM-3 only increased survival in non-ER patients [24]. Serum CD40 protein levels nearly distinguished malignant from non-malignant situations when combined with patient characteristics.…”

Recent Advances in Surface Plasmon Resonance (SPR) Technology for Detecting Ovarian Cancer Biomarkers

“…These technologies offer several advantages over conventional detection methods and have the capability to achieve a high level of accuracy, with an AUC greater than 0.9. Luminex technology utilizes fluorescent techniques and flow cytometer separation with different dyes or bead sizes, enabling accurate detection [81,82]. However, Luminex technology faces challenges in detecting low molecular weight (M W ) biomarkers in small sample volumes.…”

“…Figure 2 shows the illustration of a typical biosensor which consists of five main elements: analytes (substances to be detected), bioreceptors (specific molecules that interact with the analytes), transducers (electronics that amplify and detect signals), digital circuitry (amplifier and processor), and an interpretation system (displays the output) [27,81,97]. This enables highly sensitive detection in small volumes.…”

“…This enables highly sensitive detection in small volumes. Biosensors use various physicochemical transducers like optical, electrochemical, thermal, and piezoelectric, which are biocompatible, have a high surface-to-volume ratio, and maintain bioreceptor activity [21,81]. Biosensors can be classified based on the combination of bioreceptor-analyte, detection systems, and technologies.…”

“…Figure 2. A basic illustration of biosensors comprising of analytes, bioreceptors, bio-recognition elements, transducers with their variation, electronic system, and digital signal display [21,27,81,97].…”