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Toward a Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy.

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    This study introduces a millimeter-sized, wirelessly powered lensless CMOS image sensor for fluorescence microscopy. The device enables in-tissue biological information access for improved cancer diagnostics and continuous monitoring.

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    Area of Science:

    • Biomedical Engineering
    • Microscopy
    • Implantable Devices

    Background:

    • Accessing biological information within tissue is crucial for diagnosing and treating diseases like cancer.
    • Current clinical imaging techniques lack continuous imaging capabilities and wireless compatibility for deep tissue analysis.
    • There is a need for advanced imaging solutions to detect cellular clusters deep within tissues.

    Purpose of the Study:

    • To present a novel millimeter-sized, ultrasonically powered, lensless CMOS image sensor.
    • To demonstrate its potential for wireless fluorescence microscopy and in-tissue biological information acquisition.
    • To improve continuous detection of multicell clusters deep within tissue for applications in cancer therapy.

    Main Methods:

    • Fabrication of a 2.4 × 4.7 mm² integrated circuit (IC) using TSMC 0.18 µm technology.
    • Integration of a micro laser diode (µLD), piezoceramic for ultrasonic energy harvesting, and off-chip storage capacitors.
    • Development of a 36 × 40 pixel array with capacitive trans-impedance amplifiers, wireless power management, ultrasound communication, and a laser driver controlled by a Finite State Machine.

    Main Results:

    • The system harvests energy from acoustic waves at 2 cm depth to power the IC and enables data transfer via ultrasound backscattering (11.5 kbits/frame).
    • An off-chip capacitor stores energy for a high-power (78 mW) µLD during imaging.
    • Proof-of-concept imaging demonstrated detection of CD8 T-cells ex vivo in mouse lymph nodes, consistent with fluorescence microscopy.
    • System performance verified by detecting 140 µm features on a USAF resolution target with 32 ms exposure time.

    Conclusions:

    • The developed ultrasonically powered lensless CMOS image sensor represents a significant advancement for wireless fluorescence microscopy.
    • The platform shows promise for improved in-tissue biological information access, aiding in cancer diagnosis and therapy.
    • This technology offers potential for continuous monitoring of cellular activity deep within tissues, overcoming limitations of current imaging methods.