OPTICAL COHERENCE TOMOGRAPHY FOR BLADDER CANCER DIAGNOSIS:FROM ANIMAL STUDY TO CLINICAL DIAGNOSIS

This paper summarizes the recent technological development in our lab on cystoscopic optical coherence tomography(COCT)by integrating time-domain OCT(TDOCT)and spectral-domain OCT(SDOCT)with advanced MEMS-mirror technology for endoscopic laser scanning imaging.The COCT catheter can be integrated into the instrument channel of a commercial 22Fr rigid cystoscopic sheath for in vivo imaging of human bladder under the cystosocopic visual guidance;the axial/transverse resolutions of the COCT catheter are roughly 9μm and 12μm,respectively,and 2D COCT imaging can be performed with over 110dB dynamic range at 4–8 fps.To examine the utility and potential limitations of OCT for bladder cancer diagnosis,systemic ex vivo rat bladder carcinogenesis studies were performed to follow various morphological changes induced by tumor growth and in vivo porcine study was performed to examine the feasibility of COCT for in vivo imaging.Justified by promising results of the animal studies,preliminary clinical study was conducted on patients scheduled for operating-room cystoscopy for bladder cancers.Double-blind clinical results reveal that COCT can delineate detailed bladder architectures(e.g.,urothelium,lamina propria,muscularis)at high resolution and detect bladder cancers based on enhanced urothelial heterogeneity as a result of excessive growing nature of bladder cancers.The diagnostic sensitivity and specificity can be enhanced to 92%and 85%,respectively.Results also suggest that due to reduced imaging depth of COCT in cancerous lesions,staging of bladder cancers may be limited to Ta or T1 for non-outgrowing cancerous lesions.

An ultra-deep TSV technique enabled by the dual catalysis-based electroless plating of combined barrier and seed layers

Silicon interposers embedded with ultra-deep through-silicon vias(TSVs)are in great demand for the heterogeneous integration and packaging of opto-electronic chiplets and microelectromechanical systems(MEMS)devices.Considering the cost-effective and reliable manufacturing of ultra-deep TSVs,the formation of continuous barrier and seed layers remains a crucial challenge to solve.Herein,we present a novel dual catalysis-based electroless plating(ELP)technique by tailoring polyimide(PI)liner surfaces to fabricate dense combined Ni barrier/seed layers in ultradeep TSVs.In additional to the conventional acid catalysis procedure,a prior catalytic step in an alkaline environment is proposed to hydrolyze the PI surface into a polyamide acid(PAA)interfacial layer,resulting in additional catalysts and the formation of a dense Ni layer that can function as both a barrier layer and a seed layer,particularly at the bottom of the deep TSV.TSVs with depths larger than 500μm and no voids are successfully fabricated in this study.The fabrication process involves low costs and temperatures.For a fabricated 530-μm-deep TSV with a diameter of 70μm,the measured depletion capacitance and leakage current are approximately 1.3 pF and 1.7 pA at 20 V,respectively,indicating good electrical properties.The proposed fabrication strategy can provide a cost-effective and feasible solution to the challenge of manufacturing ultra-deep TSVs for modern 3D heterogeneous integration and packaging applications.

A robust lateral shift free(LSF)electrothermal micromirror with flexible multimorph beams

Electrothermal bimorph-based scanning micromirrors typically employ standard silicon dioxide(SiO_(2))as the electrothermal isolation material.However,due to the brittle nature of SiO_(2),such micromirrors may be incapable to survive even slight collisions,which greatly limits their application range.To improve the robustness of electrothermal micromirrors,a polymer material is incorporated and partially replaces SiO_(2) as the electrothermal isolation and anchor material.In particular,photosensitive polyimide(PSPI)is used,which also simplifies the fabrication process.Here,PSPIbased electrothermal micromirrors have been designed,fabricated,and tested.The PSPI-type micromirrors achieved an optical scan angle of±19.6°and a vertical displacement of 370μm at only 4 Vdc.With a mirror aperture size of 1 mm×1 mm,the PSPI-type micromirrors survived over 200 g accelerations from either vertical or lateral directions in impact experiments.In the drop test,the PSPI-type micromirrors survived falls to a hard floor from heights up to 21 cm.In the standard frequency sweeping vibration test,the PSPI-type micromirrors survived 21 g and 29 g acceleration in the vertical and lateral vibrations,respectively.In all these tests,the PSPI-type micromirrors demonstrated at least 4 times better robustness than SiO_(2)-type micromirrors fabricated in the same batch.

Thin ceramic PZT dual-and multi-frequency pMUT arrays for photoacoustic imaging

Miniaturized ultrasonic transducer arrays with multiple frequencies are key components in endoscopic photoacoustic imaging(PAI)systems to achieve high spatial resolution and large imaging depth for biomedical applications.In this article,we report on the development of ceramic thin-film PZT-based dual-and multi-frequency piezoelectric micromachined ultrasonic transducer(pMUT)arrays and the demonstration of their PAI applications.With chips sized 3.5mm in length or 10mm in diameter,square and ring-shaped pMUT arrays incorporating as many as 2520 pMUT elements and multiple frequencies ranging from 1 MHz to 8 MHz were developed for endoscopic PAI applications.Thin ceramic PZT with a thickness of 9μm was obtained by wafer bonding and chemical mechanical polishing(CMP)techniques and employed as the piezoelectric layer of the pMUT arrays,whose piezoelectric constant d_(31)was measured to be as high as 140 pm/V.Benefiting from this high piezoelectric constant,the fabricated pMUT arrays exhibited high electromechanical coupling coefficients and large vibration displacements.In addition to electrical,mechanical,and acoustic characterization,PAI experiments with pencil leads embedded into an agar phantom were conducted with the fabricated dual-and multi-frequency pMUT arrays.Photoacoustic signals were successfully detected by pMUT elements with different frequencies and used to reconstruct single and fused photoacoustic images,which clearly demonstrated the advantages of using dual-and multi-frequency pMUT arrays to provide comprehensive photoacoustic images with high spatial resolution and large signal-to-noise ratio simultaneously.