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BACKGROUND: Lung cancer is the world's leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. OBJECTIVE: The Cole relaxation frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. METHODS: Human testing ex vivo was conducted with NoduleScan in freshly resected lung tissue from 30 volunteer patients undergoing resection for nonsmall cell lung cancer. The CRF of the tumor and the distant normal lung tissue relative to the tumor were compared to histopathology specimens to establish a potential algorithm for point-of-care diagnosis. For animal testing in vivo, 20 mice were implanted with xenograft human lung cancer tumor cells injected subcutaneously into the right flank of each mouse. Spectral impedance measurements were taken on the tumors on live animals transcutaneously and on the tumors after euthanasia. These CRF measurements were compared to healthy mouse lung tissue. For porcine lung testing ex vivo, porcine lungs were received with the trachea. After removal of the vocal box, a ventilator was attached to pressurize the lung and simulate breathing. At different locations of the lobes, the lung's surface was cut to produce a pocket that could accommodate tumors obtained from in vivo animal testing. The tumors were placed in the subsurface of the lung, and the electrode was placed on top of the lung surface directly over the tumor but with lung tissue between the tumor and the electrode. Spectral impedance measurements were taken when the lungs were in the deflated state, inflated state, and also during the inflation-deflation process to simulate breathing. RESULTS: Among 60 specimens evaluated in 30 patients, NoduleScan allowed ready discrimination in patients with clear separation of CRF in tumor and distant normal tissue with a high degree of sensitivity (97%) and specificity (87%). In the 25 xenograft small animal model specimens measured, the CRF aligns with the separation observed in the human in vivo measurements. The CRF was successfully measured of tumors implanted into ex vivo porcine lungs, and CRF measurements aligned with previous tests for pressurized and unpressurized lungs. CONCLUSIONS: As previously shown in breast tissue, CRF in the range of 1kHz-10MHz was able to distinguish nonsmall cell lung cancer versus normal tissue. Further, as evidenced by in vivo small animal studies, perfused tumors have the same CRF signature as shown in breast tissue and human ex vivo testing. Inflation and deflation of the lung have no effect on the CRF signature. With additional development, CRF derived from spectral impedance measurements may permit point-of-care diagnosis guiding surgical resection.
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We demonstrate an electroabsorption modulator on a silicon substrate based on the quantum confined Stark effect in strained germanium quantum wells with silicon-germanium barriers. The peak contrast ratio is 7.3 dB at 1457 nm for a 10 V swing, and exceeds 3 dB from 1441 nm to 1461 nm. The novel side-entry structure employs an asymmetric Fabry-Perot resonator at oblique incidence. Unlike waveguide modulators, the design is insensitive to positional misalignment, maintaining > 3 dB contrast while translating the incident beam 87 mum and 460 mum in orthogonal directions. Since the optical ports are on the substrate edges, the wafer top and bottom are left free for electrical interconnections and thermal management.
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We present a multifunctional photonic switch that monolithically integrates an InGaAsP/InP quantum well electroabsorption modulator and an InGaAs photodiode as a part of an on-chip, InP optoelectronic circuit. The optical multifunctionality of the switch offers many configurations to allow for different optical network functions on a single chip. Here we experimentally demonstrate GHz-range optical wavelength-converting switching with only ~10 mW of absorbed input optical power, electronically controlled packet switching with a reconfiguration time of <2.5 ns, and optically controlled packet switching in <300 ps.
RESUMO
We present a dual-diode, InGaAsP/InP quantum-well modulator that incorporates a monolithically-integrated, InGaAs photodiode as a part of its on-chip, InP optoelectronic circuit. We theoretically show that such a dual-diode modulator allows for wavelength conversion with 10-dB RF-extinction ratio using 7 mW absorbed optical power at 10 Gb/s. We experimentally demonstrate unlimited wavelength conversion across 45 nm between 1525 nm and 1570 nm, and dual-wavelength broadcasting over 20 nm between 1530 nm and 1565 nm, spanning the entire C-band with >10dB RF-extinction ratio and using 3.1-6.7 mW absorbed optical power at 1.25 Gb/s.
