A Novel In Vitro Device to Deliver Induced Electromagnetic Fields to Cell and Tissue Cultures.

Abstract

We have developed a novel, to our knowledge, in vitro instrument that can deliver intermediate-frequency (100-400 kHz), moderate-intensity (up to and exceeding 6.5 V/cm pk-pk) electric fields (EFs) to cell and tissue cultures generated using induced electromagnetic fields (EMFs) in an air-core solenoid coil. A major application of these EFs is as an emerging cancer treatment modality. In vitro studies by Novocure reported that intermediate-frequency (100-300 kHz), low-amplitude (1-3 V/cm) EFs, which they called "tumor-treating fields (TTFields)," had an antimitotic effect on glioblastoma multiforme (GBM) cells. The effect was found to increase with increasing EF amplitude. Despite continued theoretical, preclinical, and clinical study, the mechanism of action remains incompletely understood. All previous in vitro studies of "TTFields" have used attached, capacitively coupled electrodes to deliver alternating EFs to cell and tissue cultures. This contacting delivery method suffers from a poorly characterized EF profile and conductive heating that limits the duration and amplitude of the applied EFs. In contrast, our device delivers EFs with a well-characterized radial profile in a noncontacting manner, eliminating conductive heating and enabling thermally regulated EF delivery. To test and demonstrate our system, we generated continuous, 200-kHz EMF with an EF amplitude profile spanning 0-6.5 V/cm pk-pk and applied them to exemplar human thyroid cell cultures for 72 h. We observed moderate reduction in cell density (<10%) at low EF amplitudes (<4 V/cm) and a greater reduction in cell density of up to 25% at higher amplitudes (4-6.5 V/cm). Our device can be readily extended to other EF frequency and amplitude regimes. Future studies with this device should contribute to the ongoing debate about the efficacy and mechanism(s) of action of "TTFields" by better isolating the effects of EFs and providing access to previously inaccessible EF regimes.

AI evidence extraction

Main findings

The authors developed a noncontacting in vitro device using an air-core solenoid coil to deliver intermediate-frequency electric fields with a characterized radial profile and reduced conductive heating. In a 72 h test using continuous 200 kHz exposure with an electric-field amplitude profile spanning 0–6.5 V/cm pk-pk, they observed a <10% reduction in cell density at <4 V/cm and up to a 25% reduction at 4–6.5 V/cm.

Outcomes measured

• Cell density (reduction) after exposure to intermediate-frequency electric fields

Limitations

• Sample size not reported in abstract
• Only one exemplar cell type (human thyroid cell cultures) described in the demonstration
• Outcome limited to cell density; other biological endpoints not described
• Exposure described as an amplitude profile spanning 0–6.5 V/cm (spatial variation), which may complicate interpretation of dose-response

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "intermediate-frequency",
        "source": "in vitro exposure device (air-core solenoid coil) delivering induced EMFs/electric fields",
        "frequency_mhz": 0.200000000000000011102230246251565404236316680908203125,
        "sar_wkg": null,
        "duration": "continuous exposure for 72 h"
    },
    "population": "Exemplar human thyroid cell cultures (in vitro)",
    "sample_size": null,
    "outcomes": [
        "Cell density (reduction) after exposure to intermediate-frequency electric fields"
    ],
    "main_findings": "The authors developed a noncontacting in vitro device using an air-core solenoid coil to deliver intermediate-frequency electric fields with a characterized radial profile and reduced conductive heating. In a 72 h test using continuous 200 kHz exposure with an electric-field amplitude profile spanning 0–6.5 V/cm pk-pk, they observed a <10% reduction in cell density at <4 V/cm and up to a 25% reduction at 4–6.5 V/cm.",
    "effect_direction": "harm",
    "limitations": [
        "Sample size not reported in abstract",
        "Only one exemplar cell type (human thyroid cell cultures) described in the demonstration",
        "Outcome limited to cell density; other biological endpoints not described",
        "Exposure described as an amplitude profile spanning 0–6.5 V/cm (spatial variation), which may complicate interpretation of dose-response"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "intermediate-frequency",
        "100-400 kHz",
        "200 kHz",
        "electric fields",
        "induced electromagnetic fields",
        "air-core solenoid coil",
        "noncontact exposure",
        "tumor-treating fields",
        "TTFields",
        "cell culture",
        "thyroid cells",
        "cell density"
    ],
    "suggested_hubs": []
}

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