Broadband single-cell detection with a coplanar series gap

Ma, Xiao; Du, Xiaotian; Multari, Caroline; Ning, Yaqing; Palego, Cristiano; Luo, Xi; Gholizadeh, V.; Cheng, Xuanhong; Hwang, J.C.M.

doi:10.1109/arftg.2015.7381459

Cited by 12 publications

(5 citation statements)

References 5 publications

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“…1 (b), where a step-like discontinuity is enforced both in the CG and in the RG parameters. Such variation is consistent with the capacitance difference between a live and a dead cell [6,10] and with a sudden increase in the medium conductivity due to intracellular ions outpouring [6]. Both facts are compatible with a compromised membrane integrity ensuing electroporation, although further evidence could be only collected through fluorescence analysis.…”

Section: B Non-linear Analysis: Microwave Intermodulationsupporting

confidence: 74%

BiCMOS microfluidic sensor for single cell label-free monitoring through microwave intermodulation

Palego¹,

Perry²,

Hancock³

et al. 2016

2016 IEEE MTT-S International Microwave Symposium (IMS)

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A novel microfluidic biosensing platform based on Bipolar-Complementary Oxide Semiconductor (BiCMOS) technology is presented. The device relies on a quadruple electrode system and a microfluidic channel that are directly integrated into the back-end-of-line (BEOL) of the BiCMOS stack. For proof of concept repeatable electrical trapping of single SW620 (colon cancer) cells in the quadruple electrode system is initially demonstrated. Additionally, for the first time a microwave intermodulation technique is used for high sensitivity dielectric spectroscopy, which could pave the way to label-free monitoring of intracellular processes and manipulation such as electroporation.

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Section: B Non-linear Analysis: Microwave Intermodulationsupporting

confidence: 74%

BiCMOS microfluidic sensor for single cell label-free monitoring through microwave intermodulation

Palego¹,

Perry²,

Hancock³

et al. 2016

2016 IEEE MTT-S International Microwave Symposium (IMS)

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“…We demonstrate that insertion loss |S21| signals are different between 15 of live vs. dead E. coli cells in the frequency range of 0.5 GHz --20 GHz, and the difference in on the order of 0.01 dB. In comparison, |S21| difference between single live and dead mammalian cells areis on the order of 0.1 dB [64]. Considering that, the volume of mammalian cells is about two to three orders of magnitude greater than that of E. coli, the order of magnitude change in S-parameters is reasonable.…”

Section: Discussionmentioning

confidence: 82%

“…It should be noted that although the model predicts a greater change of the static dielectric constant than conductivity upon E. coli death, the energy dissipation term (|S21|) better distinguish the E. coli vitality than the energy storage term (|S11|). This is likely a result of S-parameter being more sensitive to the conductivity change in the waveguide configuration used here [64]. Although membrane integrity also differs between live and dead E. coli, the small volume fraction occupied by the membrane limits accurate extraction of the membrane capacitance change, or significant contribution of the membrane electrical parameters to impedance measurements in the microwave range.…”

Section: Discussionmentioning

confidence: 98%

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Differentiation of live and heat-killed E. coli by microwave impedance spectroscopy

Multari

Palego

et al. 2018

Sensors and Actuators B: Chemical

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The detection of bacteria cells and their viability in food, water and clinical samples is critical to bioscience research and biomedical practice. In this work, we present a microfluidic device encapsulating a coplanar waveguide for differentiation of live and heat-killed E.scherichiacoli cells suspended in culture media using microwave signals over the frequency range of 0.5 GHz-20 GHz. From small populations of ∼15 E. coli cells, both the transmitted (|S21|) and reflected (|S11|) microwave signals show a difference between live and dead populations, with the difference especially significant for |S21| below 10 GHz. Analysis based on an equivalent circuit suggests that the difference is due to a reduction of the cytoplasm conductance and permittivity upon cell death. The electrical measurement is confirmed by off-chip biochemical analysis: the conductivity of cell lysate from heat-killed E. coli is 8.22% lower than that from viable cells. Furthermore, protein diffusivity increases in the cytoplasm of dead cells, suggesting the loss of cytoplasmic compactness. These changes are results of intact cell membrane of live cells acting as a semipermeable barrier, within which ion concentration and macromolecule species are tightly regulated. On the other hand, the cell membrane of dead cells is compromised, allowing ions and molecules to leak out of the cytoplasm. The loss of cytoplasmic content as well as membrane integrity areis measurable by microwave impedance sensors. Since our approach allows detection of bacterial viability in the native growth environment, it is a promising strategy for rapid point-of-care diagnostics of microorganisms as well as sensing biological agents in bioterrorism and food safety threats.

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“…Transmission mode (S21) Capacitive and conductive contrasts Living B lymphoma cell (1 cell) -nL range [27], [28], [29] kHz to 9 GHz 2-port sensor -S21 (trans.) for series configuration and S11 (refl.)…”

Section: Introductionmentioning

confidence: 99%

Accurate Characterization by Dielectric Spectroscopy up to 25 GHz of Nano-Liter Range Liquid Volume Within a Microfluidic Channel

et al. 2022

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This paper reports the design, simulation and experimental validation of an accurate liquid sensing technique in the nano-liter range. It is suitable for the detection and quantification of very small contents of liquid samples containing biological cells. The biosensor is based on an open-ended interdigitated capacitor (IDC) within a microfluidic channel. The microwave structure including the IDC is patterned in coplanar waveguide technology. The microfluidic channel is 100 µm thick and the IDC covers an area of 150 µm width and 90 µm length. This leads to a volume under analysis much lower than a nano-liter which allows the noninvasive and contactless microwave investigation of biological cells in their culture medium.This micro-device is used to extract the complex permittivity of liquid media from the measured scattering parameters within the frequency band ranging from 0.2 to 25 GHz. For ease of use, a SMAconnectorized version of the device with spring contacts probes to the biosensor is also proposed. Results concerning microparticle detection within the media are also presented, extending the use of the sensors to cellular environments.

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Broadband single-cell detection with a coplanar series gap

Cited by 12 publications

References 5 publications

BiCMOS microfluidic sensor for single cell label-free monitoring through microwave intermodulation

BiCMOS microfluidic sensor for single cell label-free monitoring through microwave intermodulation

Differentiation of live and heat-killed E. coli by microwave impedance spectroscopy

Accurate Characterization by Dielectric Spectroscopy up to 25 GHz of Nano-Liter Range Liquid Volume Within a Microfluidic Channel

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