Single droplet detection of immune checkpoints on a multiplexed electrohydrodynamic biosensor

Wuethrich, Alain; Rajkumar, Aswin Raj; Shanmugasundaram, Karthik Balaji; Khondakar, Kamil Reza; Dey, Shuvashis; Howard, Christopher B.; Sina, Abu Ali Ibn; Trau, Matt

doi:10.1039/c9an01450k

Cited by 19 publications

(15 citation statements)

References 36 publications

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“…In cancer, both soluble forms of the checkpoint, soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), have been detected in plasma, and elevated levels have been associated with advanced disease and worst prognosis for patients [ 30 ]. There are different methods to detect and measure the level of sPD-L1 in the serum and plasma [ 31 , 32 , 33 , 34 ]. Its role as a prognostic or predictive marker in lung cancer has been debated recently but the significance of this soluble protein remains uncertain [ 35 ].…”

Section: The Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.

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Section: The Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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“…Furthermore, recent advances in microfabricated devices have significantly contributed to enabling high throughput analysis. For example, a microfluidic device with an array electrode is designed to test 28 samples simultaneously in <2 h [60].…”

Section: Challenges and Future Prospective Of Liquid Mrdmentioning

confidence: 99%

Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)

et al. 2021

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Globally, non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. Minimal residual disease (MRD) is described as the existence of either isolated tumour cells or circulating tumour cells in biological liquid of patients after removal of the primary tumour without any clinical signs of cancer. Recently, liquid biopsy has been promising as a non-invasive method of disease monitoring and treatment guidelines as an MRD marker. Liquid biopsy could be used to detect and assess earlier stages of NSCLC, post-treatment MRD, resistance to targeted therapies, immune checkpoint inhibitors (ICIs) and tumour mutational burden. MRD surveillance has been proposed as a potential marker for lung cancer relapse. Principally, biosensors provide the quantitative analysis of various materials by converting biological functions into quantifiable signals. Biosensors are usually operated to detect antibodies, enzymes, DNA, RNA, extracellular vesicles (EVs) and whole cells. Here, we present a category of biosensors based on the signal transduction method for identifying biosensor-based biomarkers in liquid biopsy specimens to monitor lung cancer treatment.

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“…Hence, these sensors are time consuming and generate a response slowly. For example, a droplet loaded in the electrode can detect the PD-L1 marker and can run multiple samples at once (28 for the multiplexed biosensor on the PD-L1 marker) [ 42 ]. Advanced versions of multiplexed electrohydrodynamic biosensors have shown improved performance for biomarker detection [ 89 , 90 ].…”

Section: Biosensors For Cancer Markers and Immune Checkpoint Detectionmentioning

confidence: 99%

“…Another MICB developed by Wuethrich et al detects soluble PD-1, PD-L1, and LAG-3 in parallel in liquid biopsies, using as little as a single sample drop of approximately 20 µL volume per target immune checkpoint [ 42 ]. MICB utilizes a microfluidic sandwich immunoassay with high-affinity yeast cell-derived single chain variable fragments (ScFvs) as well as alternating current electrohydrodynamic in-situ nanofluidic mixing.…”

Section: Biosensors For Cancer Markers and Immune Checkpoint Detectionmentioning

confidence: 99%

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

et al. 2021

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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.

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Single droplet detection of immune checkpoints on a multiplexed electrohydrodynamic biosensor

Abstract: A nanofluidic mixing-enhanced biosensor enables parallel detection of soluble PD-1, PD-L1, and LAG-3 immune checkpoints in minute liquid biopsy samples.

Cited by 19 publications

References 36 publications

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)

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

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