LARLUS: laparoscopic augmented reality from laparoscopic ultrasound.

PURPOSE: This research endeavors to improve tumor localization in minimally invasive surgeries, a challenging task primarily attributable to the absence of tactile feedback and limited visibility. The conventional solution uses laparoscopic ultrasound (LUS) which has a long learning curve and is operator-dependent. METHODS: The proposed approach involves augmenting LUS images onto laparoscopic images to improve the surgeon's ability to estimate tumor and internal organ anatomy. This augmentation relies on LUS pose estimation and filtering. RESULTS: Experiments conducted with clinical data exhibit successful outcomes in both the registration and augmentation of LUS images onto laparoscopic images. Additionally, noteworthy results are observed in filtering, leading to reduced flickering in augmentations. CONCLUSION: The outcomes reveal promising results, suggesting the potential of LUS augmentation in surgical images to assist surgeons and serve as a training tool. We have used the LUS probe's shaft to disambiguate the rotational symmetry. However, in the long run, it would be desirable to find more convenient solutions.

Accuracy of an objective binocular automated phoropter for providing spectacle prescriptions.

CLINICAL RELEVANCE: Currently eye examinations are usually based on autorefraction followed by subjective refraction (SR) with a phoropter. An automated phoropter that can also perform autorefraction may facilitate the optometric workflow. BACKGROUND: The efficiency and feasibility of an objective autorefraction and correction system are assessed by comparing objective refractive measurements with SR on the same subjects and evaluating the visual acuity (VA) values obtained after the objective refractive measurement and correction. METHODS: Objective autorefraction and correction was performed on 41 subjects using an automated binocular phoropter system. The auto-phoropter performs autorefraction by wavefront measurement and corrects the spherical and cylindrical errors with tunable fluidic lenses while the patient looks at a visual display inside the instrument. The instrument outputs are optometric constants of spherical and cylindrical aberrations. After measurement and automated correction of the refractive errors, the VA values were assessed by having the subjects look at an integrated Snellen chart. The objective measurement results were statistically compared with their SR. RESULTS: The correlations between SR and objective autorefraction and correction spherical equivalents (M) were 0.98 (0.97-0.99) and 0.96 (0.93-0.98), the vertical Jackson cross cylinder (J0) were 0.96 (0.92-0.98) and 0.95 (0.91-0.97), and the oblique Jackson cross cylinder (J45) were 0.73 (0.55-0.85) and 0.82 (0.69-0.90), for the right and left eyes, respectively, with the 95% confidence interval (CI) values in parentheses. 89.0% of the 82 eyes had at least 6/7.5 VA. CONCLUSIONS: A significant agreement between the SR and objective autorefraction and correction was observed. An all-objective refractive assessment with instantaneous verification may improve the precision of eye prescriptions and possibly reduce the procedure time.

Clinical evaluation of DIAGNOVIR SARS-CoV-2 ultra-rapid antigen test performance compared to PCR-based testing.

Coronavirus Disease-19 (COVID-19) is a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of rapid antigen tests has contributed to easing the burden on healthcare and lifting restrictions by detecting infected individuals to help prevent further transmission of the virus. We developed a state-of-art rapid antigen testing system, named DIAGNOVIR, based on immune-fluorescence analysis, which can process and give the results in a minute. In our study, we assessed the performance of the DIAGNOVIR and compared the results with those of the qRT-PCR test. Our results demonstrated that the sensitivity and specificity of the DIAGNOVIR were 94% and 99.2%, respectively, with a 100% sensitivity and 96.97% specificity, among asymptomatic patients. In addition, DIAGNOVIR can detect SARS­CoV­2 with 100% sensitivity up to 5 days after symptom onset. We observed that the DIAGNOVIR Rapid Antigen Test's limit of detection (LoD) was not significantly affected by the SARS­CoV­2 variants including Wuhan, alpha (B1.1.7), beta (B.1.351), delta (B.1.617.2) and omicron (B.1.1.529) variants, and LoD was calculated as 8 × 102, 6.81 × 101.5, 3.2 × 101.5, 1 × 103, and 1 × 103.5 TCID50/mL, respectively. Our results indicated that DIAGNOVIR can detect all SARS-CoV-2 variants in just seconds with higher sensitivity and specificity lower testing costs and decreased turnover time.

Performance analysis of a compact auto-phoropter for accessible refractive assessment of the human eye.

We present the performance analysis and specifications of a portable auto-phoropter system that can be employed for fast refractive assessment of a large population. A customized Shack-Hartmann wavefront sensor is developed to accurately measure the defocus and astigmatism of the eye within ±10D and ±6D, respectively. Three fluidic lenses are designed to correct the vision in real time. A digital Snellen chart is integrated into the system to validate the accuracy of the measurement and the correction by means of achieving 20/20 vision. The refractive error of eight subjects (16 eyes) has been measured objectively (without patient's feedback) using the proposed system and the results are compared with their clinical prescription through the Bland-Altman method. It is shown that the auto-phoropter takes less than 8 s to measure and correct the eye refractive error with an accuracy of ±0.25D.

Parametric dog-bone-shaped tunable cylindrical fluidic lens.

Tunable spherical fluidic lenses are among the most essential components in adaptive optics. However, fabricating cylindrical tunable lenses has proven more challenging, mainly due to the difficulty in eliminating the defocus component. We demonstrate a parametric approach to minimize the defocus in cylindrical tunable fluidic lenses. We theoretically model and experimentally verify that a dog-bone-shaped tunable cylindrical fluidic lens exhibits almost pure cylindrical performance within the range of ${\pm{\rm 5D}}$ of astigmatism. We anticipate these results will facilitate the use of tunable cylindrical fluidic lenses in adaptive optics applications and particularly ophthalmic devices, where rapid and reliable wavefront correction is required.

A case series study of augmented reality in laparoscopic liver resection with a deformable preoperative model.

BACKGROUND: Previous work in augmented reality (AR) guidance in monocular laparoscopic hepatectomy requires the surgeon to manually overlay a rigid preoperative model onto a laparoscopy image. This may be fairly inaccurate because of significant liver deformation. We have proposed a technique which overlays a deformable preoperative model semi-automatically onto a laparoscopic image using a new software called Hepataug. The aim of this study is to show the feasibility of Hepataug to perform AR with a deformable model in laparoscopic hepatectomy. METHODS: We ran Hepataug during the procedures, as well as the usual means of laparoscopic ultrasonography (LUS) and visual inspection of the preoperative CT or MRI. The primary objective was to assess the feasibility of Hepataug, in terms of minimal disruption of the surgical workflow. The secondary objective was to assess the potential benefit of Hepataug, by subjective comparison with LUS. RESULTS: From July 2017 to March 2019, 17 consecutive patients were included in this study. AR was feasible in all procedures, with good correlation with LUS. However, for 2 patients, LUS did not reveal the location of the tumors. Hepataug gave a prediction of the tumor locations, which was confirmed and refined by careful inspection of the preoperative CT or MRI. CONCLUSION: Hepataug showed a minimal disruption of the surgical workflow and can thus be feasibly used in real hepatectomy procedures. Thanks to its new mechanism of semi-automatic deformable alignment, Hepataug also showed a good agreement with LUS and visual CT or MRI inspection in subsurface tumor localization. Importantly, Hepataug yields reproducible results. It is easy to use and could be deployed in any existing operating room. Nevertheless, comparative prospective studies are needed to study its efficacy.

Permanent tuning of optical resonant modes of chalcogenide-coated microresonators.

Chalcogenide materials are promising for optical resonant mode tuning of whispering gallery mode (WGM) microresonators due to their high nonlinearity. In this study, this phenomenon was demonstrated for Ge2Sb2Te5-coated toroidal microresonators using an optical postprocess, which utilizes the intrinsically photosensitive property of the Ge2Sb2Te5 coating. A signal laser was used to illuminate the resonator for permanent tuning of the WGMs in a sensitive manner. 0.01 nm and 0.02 nm permanent tuning of the WGMs was recorded for 5 nm and 10 nm coated resonators, respectively. This technique enables resonance matching of coupled optical resonators, which could pave the way for optoelectronic circuitries employing multiple optical microresonators.

Combining Visual Cues with Interactions for 3D-2D Registration in Liver Laparoscopy.

Augmented Reality (AR) in monocular liver laparoscopy requires one to register a preoperative 3D liver model to a laparoscopy image. This is a difficult problem because the preoperative shape may significantly differ from the unknown intraoperative shape and the liver is only partially visible in the laparoscopy image. Previous approaches are either manual, using a rigid model, or automatic, using visual cues and a biomechanical model. We propose a new approach called the hybrid approach combining the best of both worlds. The visual cues allow us to capture the machine perception while user interaction allows us to take advantage of the surgeon's prior knowledge and spatial understanding of the patient anatomy. The registration accuracy and repeatability were evaluated on phantom, animal ex vivo and patient data respectively. The proposed registration outperforms the state of the art methods both in terms of accuracy and repeatability. An average registration error below the 1 cm oncologic margin advised in the literature for tumour resection in laparoscopy hepatectomy was obtained.

Ultrasensitive Detection of Human Chorionic Gonadotropin Using Frequency Locked Microtoroid Optical Resonators.

Clean sport competition is of significant concern to many governments and sporting organizations. Highly sensitive and rapid sensors are needed to improve the detection of performance enhancing drugs in sports as athletes take diuretics to dilute the concentration of drugs in their urine and microdose under the detectable limits of current sensors. Here we demonstrate, using frequency locked microtoroid optical resonators, a 3 orders of magnitude improvement in detection limit over the current gold standard, mass spectrometry, for the common performance enhancing drug, human chorionic gonadotropin (hCG). hCG, also known as the pregnancy hormone, was detected both in simulated urine and in the urine of pregnant donors at a concentration of 1 and 3 femtomolar, respectively. We anticipate that the sensitivity provided by frequency locked optical microcavities can enable a new standard in antidoping research.

Preoperative liver registration for augmented monocular laparoscopy using backward-forward biomechanical simulation.

PURPOSE: Augmented reality for monocular laparoscopy from a preoperative volume such as CT is achieved in two steps. The first step is to segment the organ in the preoperative volume and reconstruct its 3D model. The second step is to register the preoperative 3D model to an initial intraoperative laparoscopy image. To date, there does not exist an automatic initial registration method to solve the second step for the liver in the de facto operating room conditions of monocular laparoscopy. Existing methods attempt to solve for both deformation and pose simultaneously, leading to nonconvex problems with no optimal solution algorithms. METHODS: We propose in contrast to break the problem down into two parts, solving for (i) deformation and (ii) pose. Part (i) simulates biomechanical deformations from the preoperative to the intraoperative state to predict the liver's unknown intraoperative shape by modeling gravity, the abdominopelvic cavity's pressure and boundary conditions. Part (ii) rigidly registers the simulated shape to the laparoscopy image using contour cues. RESULTS: Our formulation leads to a well-posed problem, contrary to existing methods. This is because it exploits strong environment priors to complement the weak laparoscopic visual cues. CONCLUSION: Quantitative results with in silico and phantom experiments and qualitative results with laparosurgery images for two patients show that our method outperforms the state-of-the-art in accuracy and registration time.

Colorimetric detection of ultrathin dielectrics on strong interference coatings.

Metal films covered with ultrathin lossy dielectrics can exhibit strong interference effects manifested as the broad absorption of the incident light resulting in distinct surface colors. Despite their simple bilayer structures, such surfaces have only recently been scrutinized and applied mainly to color printing. Here, we report the use of such surfaces for colorimetric detection of ultrathin dielectrics. Upon deposition of a nanometer-thick dielectric on the surface, the absorption peak red shifts, changing the surface color. The color contrast between the bare and dielectric-coated surfaces can be detected by the naked eye. The optical responses of the surfaces are characterized for nanometer-thick SiO2, Al2O3, and bovine serum albumin molecules. The results suggest that strong interference surfaces can be employed as biosensors.

Label-Free Optical Biodetection of Pathogen Virulence Factors in Complex Media Using Microtoroids with Multifunctional Surface Functionality.

Early detection of pathogens or their virulence factors in complex media has a key role in early diagnosis and treatment of many diseases. Nanomolar and selective detection of Exotoxin A, which is a virulence factor secreted from Pseudomonas aeruginosa in the sputum of Cystic Fibrosis (CF) patients, can pave the way for early diagnosis of P. aeruginosa infections. In this study, we conducted a preliminary study to demonstrate the feasibility of optical biodetection of P. aeruginosa Exotoxin A in a diluted artificial sputum mimicking the CF respiratory environment. Our surface engineering approach provides an effective biointerface enabling highly selective detection of the Exotoxin A molecules in the complex media using monoclonal anti-Exotoxin A functionalized microtoroids. The highly resilient microtoroid surface toward other constituents of the sputum provides Exotoxin A detection ability in the complex media by reproducible measurements. In this study, the limit-of-detection of Exotoxin A in the complex media is calculated as 2.45 nM.

Preliminary trial of augmented reality performed on a laparoscopic left hepatectomy.

BACKGROUND: Laparoscopic liver surgery is seldom performed, mainly because of the risk of hepatic vein bleeding or incomplete resection of the tumour. This risk may be reduced by means of an augmented reality guidance system (ARGS), which have the potential to aid one in finding the position of intrahepatic tumours and hepatic veins and thus in facilitating the oncological resection and in limiting the risk of operative bleeding. METHODS: We report the case of an 81-year-old man who was diagnosed with a hepatocellular carcinoma after an intraabdominal bleeding. The preoperative CT scan did not show metastases. We describe our preferred approach for laparoscopic left hepatectomy with initial control of the left hepatic vein and preliminary results of our novel ARGS achieved postoperatively. In our ARGS, a 3D virtual anatomical model is created from the abdominal CT scan and manually registered to selected laparoscopic images. For this patient, the virtual model was composed of the segmented left liver, right liver, tumour and median hepatic vein. RESULTS: The patient's operating time was summed up to 205 min where a blood loss of 300 cc was recorded. The postoperative course was simple. Histopathological analysis revealed the presence of a hepatocellular carcinoma with free margins. Our results of intrahepatic visualization suggest that ARGS can be beneficial in detecting the tumour, transection plane and medial hepatic vein prior to parenchymal transection, where it does not work due to the substantial changes to the liver's shape. CONCLUSIONS: As of today, we have performed eight similar left hepatectomies, with good results. Our ARGS has shown promising results and should now be attempted intraoperatively.

Wafer-scale arrays of high-Q silica optical microcavities.

On-chip high-Q microcavities possess significant potential in terms of integration of optical microresonators into functional optoelectronic devices that could be used in various applications, including biosensors, photonic-integrated circuits, or quantum optics experiments. Yet, despite the convenience of fabricating wafer-scale integrated microresonators with moderate Q values using standard microfabrication techniques, surface-tension-induced microcavities (STIMs), which have atomic-level surface roughness enabling the observation of Q values larger than 106, could only be produced using individual thermal treatment of every single microresonator within the devised area. Here, we demonstrate a facile method for large-scale fabrication of silica STIMs of various morphologies. Q values exceeding 106 are readily obtained using this technique. This study represents a significant advancement toward fabrication of wafer-scale optoelectronic circuitries.

Oligonucleotide-based label-free detection with optical microresonators: strategies and challenges.

This review targets diversified oligonucleotide-based biodetection techniques, focusing on the use of microresonators of whispering gallery mode (WGM) type as optical biosensors mostly integrated with lab-on-a-chip systems. On-chip and microfluidics combined devices along with optical microresonators provide rapid, robust, reproducible and multiplexed biodetection abilities in considerably small volumes. We present a detailed overview of the studies conducted so far, including biodetection of various oligonucleotide biomarkers as well as deoxyribonucleic acids (DNAs), ribonucleic acids (RNAs) and proteins. We particularly advert to chemical surface modifications for specific and selective biosensing.

Real-Time and Selective Detection of Single Nucleotide DNA Mutations Using Surface Engineered Microtoroids.

Mictoroids, as optical biosensors, can provide beneficial biosensing platforms to understand DNA alterations. These alterations could have significant clinical importance, such as the case of Pseudomonas aeruginosa, which is a commonly found pathogen in Cystic Fibrosis (CF) patients-causing poor prognosis by undergoing mutations during disease steps, gaining virulence and drug resistance. To provide a preliminary diagnosis platform for early-stage bacterial mutations, biosensing with a selective microtoroid surface was suggested. For this purpose, microtoroids with high quality factors were fabricated. The microtoroid surfaces were coated with (3-aminopropyl) triethoxysilane (APTES)/trimethylmethoxysilane (TMMS) mixed silane solution followed by EDC/NHS chemistry for covalent conjugation of DNA probes. Ethanolamine capping was applied to avoid unspecific interactions. The confocal studies confirmed homogeneous functionalization of the microtoroid surface. The DNA hybridization was demonstrated to be affected from the probe length. The optical biosensors showed a significant response (∼22 pm) to the complementary strand of the mutated type P. aeruginosa DNA, while showing substantially low and late response (∼5 pm) to the point mismatch strand. The limit of detection (LOD) for the complementary strand was calculated as 2.32 nM. No significant response was obtained for the noncomplementary strand. The results showed the microtoroids possessed selective surfaces in terms of distinguishing DNA alterations.

Label-Free Biosensing with High Selectivity in Complex Media using Microtoroidal Optical Resonators.

Although label-free biosensors comprised of optical microcavities inherently possess the capability of resolving molecular interactions at individual level, this extreme sensitivity restricts their convenience for large scale applications by inducing vulnerability towards non-specific interactions that readily occur within complex media. Therefore, the use of optical microresonators for biosensing is mostly limited within strictly defined laboratory conditions, instead of field applications as early detection of cancer markers in blood, or identification of contamination in food. Here, we propose a novel surface modification strategy suitable for but not limited to optical microresonator based biosensors, enabling highly selective biosensing with considerable sensitivity as well. Using a robust, silane-based surface coating which is simultaneously protein resistant and bioconjugable, we demonstrate that it becomes possible to perform biosensing within complex media, without compromising the sensitivity or reliability of the measurement. Functionalized microtoroids are successfully shown to resist nonspecific interactions, while simultaneously being used as sensitive biological sensors. This strategy could pave the way for important applications in terms of extending the use of state-of-the-art biosensors for solving problems similar to the aforementioned.

The interplay between plasma membrane and endoplasmic reticulum Ca(2+)ATPases in agonist-induced temporal Ca(2+) dynamics.

A change in the intracellular free Ca(2+) concentration ([Ca(2+)]i) functions as a transmitter for signal transduction and shows a broad temporal pattern. Even genetically homogeneous cell types show different Ca(2+) response patterns under permanent agonist stimulation. In Ca(2+) signaling, the dynamics of the Ca(2+) release from the Ca(2+) channels during continuous agonist stimulation and the simultaneous effect of the pumps are unclear. In this study, the dynamic interaction of the Ca(2+) ATPases in the plasma membrane (PMCA) and the endoplasmic reticulum membrane (SERCA) during continuous ACh stimulation is monitored using Fluo-3 and Fura-2 loaded HEK 293 cells. We characterize Ca(2+) release patterns at the sub-maximal and maximal stimulation doses in the absence of extracellular Ca(2+). We analyze the responses regarding their types, oscillation frequency and response times. La(3+) (PMCA blocker) do not change the frequency and time courses in sub-maximal ACh treatment, while with the maximal stimulation oscillation frequency increase as oscillations superimpose on robust release, and response time of [Ca(2+)]i is elongated. A similar effect of La(3+) is observed in quantal Ca(2+) release phenomenon. In the presence of CPA, a SERCA blocker, oscillations are completely abolished, but response time does not change. We also observe that during continuous receptor stimulation, Ca(2+) release do not cease. These data may suggest that Ca(2+) release continues during agonist stimulation, but SERCA and PMCA form a new steady state and return [Ca(2+)]i to its physiological concentration.

Phosphonate based organosilane modification of a simultaneously protein resistant and bioconjugable silica surface.

A facile method to coat silica surfaces with THPMP is introduced, forming simultaneously a protein resistant and bioconjugable surface. The coating is experimentally identified and its anti-fouling and bioconjugable characteristics are demonstrated.

Impact of mesoporous silica nanoparticle surface functionality on hemolytic activity, thrombogenicity and non-specific protein adsorption.

Although numerous mesoporous silica nanoparticle (MSN) drug carriers and theranostic agents with various surface functionalities have been designed in the last decade, their biocompatibility remains a matter of intensive debate. Here, we systematically evaluated interactions of a series of MSNs possessing different surface functional groups (ionic, polar, neutral, and hydrophobic) with blood constituents, in terms of their hemolytic activity, thrombogenicity, and adsorption of blood proteins on their surfaces. Using a hemolysis assay we showed that surface functionalization can reduce or even completely prevent the hemolytic activity of bare MSNs. We investigated thrombogenicity of MSNs by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). We observed that none of the MSNs used in this study exhibit significant thrombogenic activity. Lastly, we examined non-specific protein adsorption on MSN surfaces using human serum albumin (HSA) and gamma globulins (γGs) and found that surface functionalization with ionic groups can greatly reduce protein adsorption. Demonstration of the surface functionalization having a crucial impact on blood compatibility might serve as a guideline for further investigation related to the design of mesoporous silica systems for biomedical applications, and shed light on research towards the ultimate goal of developing smart theranostic systems.