Ultrahigh-Throughput, Real-Time Flow Cytometry for Rare Cell Quantification from Whole Blood

We present an ultrahigh-throughput, real-time fluorescence cytometer comprising a viscoelastic microfluidic system and a complementary metal–oxide-semiconductor (CMOS) linear image sensor-based detection system. The flow cytometer allows for real-time quantification of a variety of fluorescence spec...

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Published inACS sensors Vol. 9; no. 1; pp. 474 - 482
Main Authors Aslan, Mahmut Kamil, Meng, Yingchao, Zhang, Yanan, Weiss, Tobias, Stavrakis, Stavros, deMello, Andrew J.
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 26.01.2024
Subjects
Flow Cytometry - methods
Humans
Microfluidics
Neoplastic Cells, Circulating
flow cytometry
real-time
circulating tumor cells
fluorescence
microfluidics
high-throughput
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Abstract We present an ultrahigh-throughput, real-time fluorescence cytometer comprising a viscoelastic microfluidic system and a complementary metal–oxide-semiconductor (CMOS) linear image sensor-based detection system. The flow cytometer allows for real-time quantification of a variety of fluorescence species, including micrometer-sized particles and cells, at analytical throughputs in excess of 400,000 species per second. The platform integrates a custom C++ control program and graphical user interface (GUI) to allow for the processing of raw signals, adjustment of processing parameters, and display of fluorescence intensity histograms in real time. To demonstrate the efficacy of the platform for rare event detection and its utility as a basic clinical tool, we measure and quantify patient-derived circulating tumor cells (CTCs) in peripheral blood, realizing that detection has a sensitivity of 6 CTCs per million blood cells (0.000006%) with a volumetric throughput of over 3 mL/min.
AbstractList We present an ultrahigh-throughput, real-time fluorescence cytometer comprising a viscoelastic microfluidic system and a complementary metal-oxide-semiconductor (CMOS) linear image sensor-based detection system. The flow cytometer allows for real-time quantification of a variety of fluorescence species, including micrometer-sized particles and cells, at analytical throughputs in excess of 400,000 species per second. The platform integrates a custom C++ control program and graphical user interface (GUI) to allow for the processing of raw signals, adjustment of processing parameters, and display of fluorescence intensity histograms in real time. To demonstrate the efficacy of the platform for rare event detection and its utility as a basic clinical tool, we measure and quantify patient-derived circulating tumor cells (CTCs) in peripheral blood, realizing that detection has a sensitivity of 6 CTCs per million blood cells (0.000006%) with a volumetric throughput of over 3 mL/min.
Author Zhang, Yanan
Weiss, Tobias
Meng, Yingchao
Aslan, Mahmut Kamil
Stavrakis, Stavros
deMello, Andrew J.
AuthorAffiliation Clinical Neuroscience Center
Department of Neurology
Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences
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  givenname: Mahmut Kamil
  surname: Aslan
  fullname: Aslan, Mahmut Kamil
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  email: andrew.demello@chem.ethz.ch
  organization: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences
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real-time
circulating tumor cells
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high-throughput
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SubjectTerms Flow Cytometry - methods
Humans
Microfluidics
Neoplastic Cells, Circulating
Title Ultrahigh-Throughput, Real-Time Flow Cytometry for Rare Cell Quantification from Whole Blood
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