Natural killer cell detection, quantification, and subpopulation identification on paper microfluidic cell chromatography using smartphone-based machine learning classification

Zenhausern, Ryan; Day, Alexander S.; Safavinia, Babak; Han, Seungmin; Rudy, Paige E.; Won, Young‐Wook; Yoon, Jeong‐Yeol

doi:10.1016/j.bios.2021.113916

Cited by 19 publications

(8 citation statements)

References 30 publications

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“…In our experiment, 1% blood sample had better linearity than DI water. This pattern has often been seen in previous studies as well 48 , 49 . In a study that detected ROR1 + cancer cells in buffy coat blood samples, the linearity of aggregation did not increase with cell concentration.…”

Section: Discussionsupporting

confidence: 87%

“…In the first set of experiments, we tested two monoclonal antibodies targeting B. burgdorferi recombinant OspA in a simple fluid of DI water and a complex biological fluid of blood, diluted to 1%. For this class of assay, whole blood is traditionally diluted to 10% and/or 1%, because whole blood viscosity prevents flow in microfluidics 48 , 49 . In our experiment, 1% blood sample had better linearity than DI water.…”

Section: Discussionmentioning

confidence: 99%

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A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood

Kim

Samanta

Nguyen

et al. 2023

Sci Rep

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There are no assays for detecting B. burgdorferi antigen in blood of infected Lyme disease individuals. Here, we provide proof-of-principle evidence that we can quantify B. burgdorferi antigen in spiked blood using a portable smartphone-based fluorescence microscope that measures immunoagglutination on a paper microfluidic chip. We targeted B. burgdorferi OspA to develop a working prototype and added examples of two antigens (OspC and VlsE) that have diagnostic value for discrimination of Lyme disease stage. Using an extensively validated monoclonal antibody to OspA (LA-2), detection of OspA antigen had a broad linear range up to 100 pg/mL in 1% blood and the limit of detection (LOD) was 100 fg/mL (= 10 pg/mL in undiluted blood), which was 1000 times lower than our target of 10 ng/mL. Analysis of the two other targets was done using polyclonal and monoclonal antibodies. OspC antigen was detected at LOD 100 pg/mL (= 10 ng/mL of undiluted blood) and VlsE antigen was detected at LOD 1–10 pg/mL (= 0.1–1 ng/mL of undiluted blood). The method is accurate and was performed in 20 min from sample to answer. When optimized for detecting several B. burgdorferi antigens, this assay may differentiate active from past infections and facilitate diagnosis of Lyme disease in the initial weeks of infection, when antibody presence is typically below the threshold to be detected by serologic methods.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood

Kim

Samanta

Nguyen

et al. 2023

Sci Rep

Self Cite

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“…Detection of cytokines in biological samples requires the use of analytical methods characterized by high sensitivity and specificity, taking into account the very low levels of these biomarkers and the complex matrix in which they are found. 66,67 Conventional detection methods were developed starting from the immunological methods such as enzymelinked immunosorbent assay (ELISA), 67,68 hyphenated chromatographic methods combining high-performance liquid chromatography with diverse detection methods: mass spectrometry (MS), UV-VIS spectrophotometry, and electrochemical methods, 69 as well as several spectrophotometric techniques 70 and DNA-based methods. 69 The special requirements for analytical parameters that are suitable for the detection of these biomarkers have led researchers to look for alternative methods.…”

Section: Analytical Methods Applied For Cytokines Determination In Bi...mentioning

confidence: 99%

Unrevealing the connection between real sample analysis and analytical method. The case of cytokines

Irimes

Tertiş

Oprean

et al. 2023

Medicinal Research Reviews

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Cytokines are compounds that belong to a special class of signaling biomolecules that are responsible for several functions in the human body, being involved in cell growth, inflammatory, and neoplastic processes. Thus, they represent valuable biomarkers for diagnosing and drug therapy monitoring certain medical conditions. Because cytokines are secreted in the human body, they can be detected in both conventional samples, such as blood or urine, but also in samples less used in medical practice such as sweat or saliva. As the importance of cytokines was identified, various analytical methods for their determination in biological fluids were reported. The gold standard in cytokine detection is considered the enzyme‐linked immunosorbent assay method and the most recent ones have been considered and compared in this study. It is known that the conventional methods are accompanied by a few disadvantages that new methods of analysis, especially electrochemical sensors, are trying to overcome. Electrochemical sensors proved to be suited for the elaboration of integrated, portable, and wearable sensing devices, which could also facilitate cytokines determination in medical practice.

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“…Contrarily, a paper-based microfluidic device for cell chromatography was utilized to analyze the proportion of CD56 bright and CD56 dim NK-92 cells. 270 The cells flowed through the paper-based device containing anti-CD56 fluorescent nanoparticles, and heterogeneous NK cells could be distinguished based on size differences because IL-2-starved CD56 dim NK-92 cells were smaller than CD56 bright ones. Consequently, CD56 bright NK-92 cells were trapped near the inlet of the device owing to increased flow resistance.…”

Section: Future Of Adoptive Cell Immunotherapy Through Microfluidic S...mentioning

confidence: 99%

Expanding CAR-T cell immunotherapy horizons through microfluidics

Kim,

Lim

et al. 2024

Lab Chip

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Natural killer cell detection, quantification, and subpopulation identification on paper microfluidic cell chromatography using smartphone-based machine learning classification

Cited by 19 publications

References 30 publications

A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood

A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood

Unrevealing the connection between real sample analysis and analytical method. The case of cytokines

Expanding CAR-T cell immunotherapy horizons through microfluidics

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