Year: 2018
Type: article
Abstract: Cellular senescence plays an important role in organismal aging and age-related diseases. However, it is challenging to isolate low numbers of senescent cells from small volumes of biofluids for downstream analysis. Furthermore, there is no technology that could selectively remove senescent cells in a high-throughput manner. In this work, we developed a novel microfluidic chip platform, termed senescence chip, for ultrahigh-throughput isolation and removal of senescent cells. The core component of our senescence chip is a slanted and tunable 3D micropillar array with a variety of shutters in the vertical direction for rapid cell sieving, taking advantage of the characteristic cell size increase during cellular senescence. The 3D configuration achieves high throughput, high recovery rate, and device robustness with minimum clogging. We demonstrated proof-of-principle applications in isolation and enumeration of senescent mesenchymal stem cells (MSCs) from undiluted human whole blood, and senescent cells from mouse bone marrow after total body irradiation, with the single-cell resolution. After scale-up to a multilayer and multichannel structure, our senescence chip achieved ultrahigh-throughput removal of senescent cells from human whole blood with an efficiency of over 70% at a flow rate of 300 ml/hr. Sensitivity and specificity of our senescence chips could be augmented with implementation of multiscale size separation, and identification of background white blood cells using their cell surface markers such as CD45. With the advantages of high throughput, robustness, and simplicity, our senescence chips may find wide applications and contribute to diagnosis and therapeutic targeting of cellular senescence.
Source: Aging Cell
DOI: 10.1111/acel.12722
Authors: Yuchao Chen, Pan Mao, Antoine M. Snijders, Daojing Wang
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Center for Complementary and Integrative Health
Awards: AD-MS Chips for Biofluids-Based Diagnosis of Alzheimer's Disease, Senescence-Chips for Radiation Biodosimetry, G2749707749, Picoelectrospray Ionization Mass Spectrometry for Top-down Proteomics, G3089326124, Picoelectrospray Ionization Mass Spectrometry for Top-down Proteomics, G3863494725, G4597545058, G5094328609, G6778851630, AD-MS Chips for Biofluids-Based Diagnosis of Alzheimer's Disease, G8172376892, G8374358241, Microfluidic Chips for Biomonitoring, G9000022924, G9000054515, G9000196170, G9000199284, G9000249338, G9000340877
OpenAlex ID: W2784073442