Biosensors for immune cell analysis—A perspective

Abstract

Massively parallel analysis of single immune cells or small immune cell colonies for disease detection, drug screening, and antibody production represents a "killer app" for the rapidly maturing microfabrication and microfluidic technologies. In our view, microfabricated solid-phase and flow cytometry platforms of the future will be complete with biosensors and electrical/mechanical/optical actuators and will enable multi-parametric analysis of cell function, real-time detection of secreted signals, and facile retrieval of cells deemed interesting.

Surface‐Micromachined Microfiltration Membranes for Efficient Isolation and Functional Immunophenotyping of Subpopulations of Immune Cells

“…[1–4] Leukocytes (white blood cells) are important blood constituents that play a major role in innate and adaptive immune responses against pathogenic infections, allergic conditions, and malignancies. Leukocytes are a heterogeneous mixture of multiple cell subsets (granulocytes, lymphocytes, and monocytes) defined by their morphology, surface antigen expression, and production of cytokines – small proteins for intercellular communications between leukocytes of the same type (homotypic) or different types (heterotypic).…”

“…[5–8] The numbers, proportions and functional responses of leukocyte subsets change drastically in the presence of infections, malignancies, and autoimmune disorders, making analysis of leukocyte subpopulations particularly valuable in the diagnosis and monitoring of diseases. [4,9] For example, human immunodeficiency virus (HIV) infection causes depletion of CD4+ T cells in peripheral blood and other lymphoid tissues. [1,10–12] As a result, the absolute counts of CD4+ T cells and the ratio of CD4+/ CD8+ T cells are commonly used as indicators of the onset of the acquired immunodeficiency syndrome (AIDS) and as benchmarks for the initiation of antiviral therapy to treat AIDS.…”

Emerging Microfluidic Tools for Functional Cellular Immunophenotyping: A New Potential Paradigm for Immune Status Characterization

“…Immune cells in blood constitute a complex, heterogeneous mixture of multiple cell types including granulocytes, lymphocytes, and monocytes (Re and Strominger, 2004; Gordon and Taylor, 2005; Kaech and Wherry, 2007; O’Shea et al, 2008). The numbers, proportions, and cytolytic and cytokine production activities of leukocyte subsets change drastically in the presence of infections, malignancies, and autoimmune disorders (Revzin et al, 2012). As such, there is a significant need for reliable technologies that can perform rapid and accurate functional cellular immunophenotyping on patient immune cells and their subtypes to define and characterize the “immune phenotype” of patients.…”

Photodegradable Hydrogels for Capture, Detection, and Release of Live Cells

“…These advantages are related to small volumes, controlled washing conditions, miniature size of the device, and multiplexing capabilities. [3] However, the ability to capture various immune cells and analyze the function of these cells needs to be combined with the possibility of selectively retrieving cells of interest by making use of either their surface marker expression or function. For example, physicochemical stimulation (e.g., exposure to EDTA or enzymes or temperature control) can be applied to retrieve cells from the surfaces.…”