Front Cover: Implantable self‐aligning fiber‐optic optomechanical devices for in vivo intraocular pressure‐sensing in artificial cornea

This work addresses an unmet clinical need, that of glaucoma monitoring through intraocular pressure (IOP) interrogation in patients with artificial corneas (keratoprost hesis). We demonstrate direct integration of a low‐drift, fiber‐optic Fabry‐Perot pressure sensor embedded in the keratoprosthesis via rapid, non‐contact micromagnetic fiber alignment. IOP interrogation is achieved by using white‐light interferometry, which provides sub‐mmHg IOP sensitivity. Further details can be found in the article by Pui‐Chuen Hui, Katia Shtyrkova, Chengxin Zhou, et al. ( e202000031 ).

     

Simultaneous fingerprint and high‐wavenumber fiber‐optic Raman spectroscopy enhances real‐time in vivo diagnosis of adenomatous polyps during colonoscopy

Colorectal cancer can be prevented if detected early (e.g., precancerous polyps‐adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber‐optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real‐time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber‐optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800–1800 cm^–1) and HW (i.e., 2800–3600 cm^–1) Raman spectra from colorectal tissue subsurface (<200 µm) for real‐time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be attributed to changes in inter‐ and intra‐cellular proteins, lipids, DNA and water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.

     

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Corneal transplantation by full‐thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high‐quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept‐source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude‐scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth‐intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.      

Visible‐near infrared‐II skull optical clearing window for in vivo cortical vasculature imaging and targeted manipulation

Skull optical clearing window permits us to perform in vivo cortical imaging without craniotomy, but mainly limits to visible (vis)‐near infrared (NIR)‐I light imaging. If the skull optical clearing window is available for NIR‐II, the imaging depth will be further enhanced. Herein, we developed a vis‐NIR‐II skull optical clearing agents with deuterium oxide instead of water, which could make the skull transparent in the range of visible to NIR‐II. Using a NIR‐II excited third harmonic generation microscope, the cortical vasculature of mice could be clearly distinguished even at the depth of 650 μm through the vis‐NIR‐II skull clearing window. The imaging depth after clearing is close to that without skull, and increases by three times through turbid skull. Furthermore, the new skull optical clearing window promises to realize NIR‐II laser‐induced targeted injury of cortical single vessel. This work enhances the ability of NIR‐II excited nonlinear imaging techniques for accessing to cortical neurovasculature in deep tissue.     

A rapid bio‐optical sensor for diagnosing Q fever in clinical specimens

Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and Ebola, have highlighted the need for rapid and accurate diagnostic assays that can be used to aid pathogen control. Q fever is a zoonotic disease caused by the transmission of Coxiella burnetii that can cause serious illness in humans through aerosols and is considered a potential bioterrorism agent. However, the existing assays are not suitable for the detection of this pathogen due to its low levels in real samples. We here describe a rapid bio‐optical sensor for the accurate detection of Q fever and validate its clinical utility. By combining a bio‐optical sensor, that transduces the presence of the target DNA based on binding‐induced changes in the refractive index on the waveguide surface in a label‐free and real‐time manner, with isothermal DNA amplification, this new diagnostic tool offers a rapid (<20 min), 1‐step DNA amplification/detection method. We confirmed the clinical sensitivity (>90%) of the bio‐optical sensor by detecting C. burnetii in 11 formalin‐fixed, paraffin‐embedded liver biopsy samples from acute Q fever hepatitis patients and in 16 blood plasma samples from patients in which Q fever is the cause of fever of unknown origin.      

Experimental evidence for negative turgor pressure in small leaf cells of Robinia pseudoacacia L versus large cells of Metasequoia glyptostroboides Hu et W.C.Cheng. 1. Evidence from pressure‐volume curve analysis of dead tissue.

This paper provides a mini‐review of evidence for negative turgor pressure in leaf cells starting with experimental evidence in the late 1950s and ending with biomechanical models published in 2014. In the present study, biomechanical models were used to predict how negative turgor pressure might be manifested in dead tissue, and experiments were conducted to test the predictions. The main findings were as follows: (i) Tissues killed by heating to 60 or 80 °C or by freezing in liquid nitrogen all became equally leaky to cell sap solutes and all seemed to pass freely through the cell walls. (ii) Once cell sap solutes could freely pass the cell walls, the shape of pressure‐volume curves was dramatically altered between living and dead cells. (iii) Pressure‐volume curves of dead tissue seem to measure negative turgor defined as negative when inside minus outside pressure is negative. (iv) Robinia pseudoacacia leaves with small palisade cells had more negative turgor than Metasequoia glyptostroboides with large cells. (v) The absolute difference in negative turgor between R. pseudoacacia and M. glyptostroboides approached as much as 1.0 MPa in some cases. The differences in the manifestation of negative turgor in living versus dead tissue are discussed.