Cystatin C and sarcopenia index are associated with cardiovascular and all-cause death among adults in the United States.

OBJECTIVES: This study aimed to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death in general population. METHODS: Data of participants from the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2004 were used and all participants were followed up regularly until December 31, 2019. Multivariable Cox analysis was used to investigate the association of cystatin C, serum creatinine and sarcopenia index with cardiovascular and all-cause death. Restricted cubic spline was conducted to evaluate the nonlinear association. RESULTS: A total of 9894 participants with a mean age of 45.64 years were enrolled and followed up for a mean duration of 15.62 ± 4.68 years. Approximately 50.3% were male and there were a total of 2681 all-cause deaths and 691 cardiovascular deaths recorded during the follow-up period. In final adjusted model, compared with the first quartile of cystatin C (< 0.659 mg/L), the risk of cardiovascular and all-cause death increased 2.36-fold and 1.71-fold for participants in the fourth quartile (≥ 0.877 mg/L) (HR: 3.36, 95% CI: 2.06-5.46, P < 0.001; HR: 2.71, 95% CI: 2.17-3.38, P < 0.001; respectively). Furthermore, a higher sarcopenia index (< 88.41 vs. ≥125.52) was associated with the reduced risk of cardiovascular death (HR: 0.41, 95% CI: 0.31-0.53, P < 0.001) as well as all-cause death (HR: 0.41, 95% CI: 0.35-0.49, P < 0.001). Additionally, restricted cubic splines showed that there was a nonlinear relationship between sarcopenia index levels and all-cause death while there was a linear relationship between sarcopenia index levels and cardiovascular death. CONCLUSIONS: Higher sarcopenia index was associated with the decreased risk of cardiovascular and all-cause death in general population in the United States. Elevated cystatin C was positively associated with cardiovascular and all-cause death.

Hyperuricemia is associated with heart failure readmission in patients with heart failure and preserved ejection fraction-an observational study in Chinese.

BACKGROUND AND AIMS: This study aimed to explore the association between hyperuricemia and heart failure (HF) readmission in HF patients with preserved ejection fraction (HFpEF) because the impact of hyperuricemia on the prognosis of these patients has not been fully understood. METHODS AND RESULTS: This retrospective observational study included 538 hospitalized patients diagnosed with HFpEF. A total of 57.6 % of patients with HFpEF suffered from hyperuricemia (serum uric acid (SUA) was >7 mg/dL in men and >6 mg/dL in women). Compared to those without hyperuricemia, patients with hyperuricemia were more likely to be female (62.6 % vs. 53.9 %, p = 0.044) and older (78.0 ± 8.4 vs. 75.9 ± 9.0 years, p = 0.008). Our Cox analysis revealed that SUA level (hazard ratio (HR) = 1.158, 95 % confidence interval (CI): 1.087-1.234, p<0.001) and hyperuricemia (HR = 1.846, 95 % CI: 1.308-2.606, p<0.001) were associated with HF readmission in patients with HFpEF, respectively. Kaplan-Meier analysis showed that patients with hyperuricemia had a significantly worse prognosis (p<0.001). The receiver operating characteristic analysis revealed that the area under the ROC curve of SUA for predicting HF readmission was 0.6276 (95 % CI: 0.5763-0.6790) and a designated cut-off value of 7.53 mg/dL. CONCLUSIONS: Hyperuricemia is a common comorbidity among patients with HFpEF. Moreover, SUA level and hyperuricemia have been shown to be associated with HF readmission. Therefore, it is meaningful to monitor SUA levels in patients with HFpEF during the whole treatment period of HF. Whereas, whether intervention of hyperuricemia could benefit patients with HFpEF needs further studies.

Structured modulation multi-height microscopy for high-resolution imaging.

Conventional multi-height microscopy techniques introduce different object-to-detector distances to obtain multiple measurements for phase retrieval. However, surpassing the diffraction limit imposed by the numerical aperture (NA) of the objective lens remains a challenging task. Here, we report a novel structured modulation multi-height microscopy technique for quantitative high-resolution imaging. In our platform, a thin diffuser is placed in between the sample and the objective lens. By translating the diffuser to different axial positions, a sequence of modulated intensity images is captured for reconstruction. The otherwise inaccessible high-resolution object information can thus be encoded into the optical system for detection. In the construction process, we report a ptychographic phase retrieval algorithm to recover the existing wavefront of the complex object. We validate our approach using a resolution target, a phase target, and various biological samples. We demonstrate a ∼4-fold resolution gain over the diffraction limit. We also demonstrate our approach to achieve a 6.5 mm by 4.3 mm field of view and a half-pitch resolution of 1.2 µm. The reported methodology provides a portable, turnkey solution for quantitative high-resolution imaging with potential applications in disease diagnosis, sample screening, and other fields.

Air-laser-based coherent Raman spectroscopy of atmospheric molecules in a filamentary plasma grating.

Coherent Raman spectroscopy (CRS) with air-laser-based hybrid femtosecond/picosecond (fs/ps) pulses has shown promising potential for remote detection and surveillance of atmospheric species with high temporal and frequency resolution. Here, to enhance the sensitivity and extend the detection distance, we generate the CRS spectra of air molecules in situ in a filamentary plasma grating, and show that the grating can efficiently enhance the intensities of the coherent vibrational Raman lines of N2, O2, and N2 + by 2-3 orders of magnitude at an extended distance. By examining the intensities of the Raman lines, fs-pulsed supercontinuum, and ps-pulsed air laser produced under different grating conditions, we reveal that the optimization of the Raman lines is achieved by the dynamic balance between the supercontinuum-induced vibrational coherence and air-laser-induced polarization of the air species.

GRASS: Learning Spatial-Temporal Properties From Chainlike Cascade Data for Microscopic Diffusion Prediction.

Information diffusion prediction captures diffusion dynamics of online messages in social networks. Thus, it is the basis of many essential tasks such as popularity prediction and viral marketing. However, there are two thorny problems caused by the loss of spatial-temporal properties of cascade data: "position-hopping" and "branch-independency." The former means no exact propagation relationship between any two consecutive infected users. The latter indicates that not all previously infected users contribute to the prediction of the next infected user. This article proposes the GRU-like Attention Unit and Structural Spreading (GRASS) model for microscopic cascade prediction to overcome the above two problems. First, we introduce the attention mechanism into the gated recurrent unit (GRU) component to expand the restricted receptive field of the recurrent neural network (RNN)-type module, thus addressing the "position-hopping" problem. Second, the structural spreading (SS) mechanism leverages structural features to filter out related users and controls the generation of cascade hidden states, thereby solving the "branch-independency" problem. Experiments on multiple real-world datasets show that our model significantly outperforms state-of-the-art baseline models on both hits@κ and map@κ metrics. Furthermore, the visualization of latent representations by t-distributed stochastic neighbor embedding (t-SNE) indicates that our model makes different cascades more discriminative during the encoding process.

Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction.

BACKGROUND: Nocturnal hypertension is reported as a risk factor for cardiovascular disease. This study aimed to explore the potential association between nocturnal hypertension and heart failure (HF) rehospitalization in patients with HF with preserved ejection fraction (HFpEF). METHODS: A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study. Cox regression analysis was used to reveal the potential association between nighttime blood pressure (BP) levels, nocturnal hypertension and nocturnal BP patterns and HF rehospitalization. Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups. RESULTS: There were 537 patients with HFpEF were included in the final analysis. The mean age of the study population was 77.14 ± 8.68 years, and 41.2% of patients were men. After a median follow-up duration of 10.93 (4.19-21.13) months, 176 patients (32.7%) with HFpEF were readmitted for HF. Cox regression analysis had revealed that nighttime systolic BP level [hazards ratio (HR) = 1.018, 95% CI: 1.008-1.028, P = 0.001], nighttime diastolic BP level (HR = 1.024, 95% CI: 1.007-1.042, P = 0.007), nocturnal hypertension (HR = 1.688, 95% CI: 1.229-2.317, P = 0.001) were associated with HF rehospitalization. Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate (log-rank P < 0.001). Furthermore, patients with a riser pattern had a higher risk of HF rehospitalization (HR = 1.828, 95% CI: 1.055-3.166, P = 0.031) and lower event-free survival rate (log-rank P = 0.003) than those with a dipper pattern. These findings were also confirmed in patients with HFpEF and hyperuricemia. CONCLUSIONS: Nighttime BP levels, nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF, and prominently in patients with HFpEF and hyperuricemia. Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

FedDroidMeter: A Privacy Risk Evaluator for FL-Based Android Malware Classification Systems.

In traditional centralized Android malware classifiers based on machine learning, the training sample uploaded by users contains sensitive personal information, such as app usage and device security status, which will undermine personal privacy if used directly by the server. Federated-learning-based Android malware classifiers have attracted much attention due to their privacy-preserving and multi-party joint modeling. However, research shows that indirect privacy inferences from curious central servers threaten this framework. We propose a privacy risk evaluation framework, FedDroidMeter, based on normalized mutual information in response to user privacy requirements to measure the privacy risk in FL-based malware classifiers. It captures the essential cause of the disclosure of sensitive information in classifiers, independent of the attack model and capability. We performed numerical assessments using the Androzoo dataset, the baseline FL-based classifiers, the privacy-inferred attack model, and the baseline methodology of privacy evaluation. The experimental results show that FedDroidMeter can measure the privacy risks of the classifiers more effectively. Meanwhile, by comparing different models, FL, and privacy parameter settings, we proved that FedDroidMeter could compare the privacy risk between different use cases equally. Finally, we preliminarily study the law of privacy risk in classifiers. The experimental results emphasize the importance of providing a systematic privacy risk evaluation framework for FL-based malware classifiers and provide experience and a theoretical basis for studying targeted defense methods.

Spatial- and Fourier-domain ptychography for high-throughput bio-imaging.

First envisioned for determining crystalline structures, ptychography has become a useful imaging tool for microscopists. However, ptychography remains underused by biomedical researchers due to its limited resolution and throughput in the visible light regime. Recent developments of spatial- and Fourier-domain ptychography have successfully addressed these issues and now offer the potential for high-resolution, high-throughput optical imaging with minimal hardware modifications to existing microscopy setups, often providing an excellent trade-off between resolution and field of view inherent to conventional imaging systems, giving biomedical researchers the best of both worlds. Here, we provide extensive information to enable the implementation of ptychography by biomedical researchers in the visible light regime. We first discuss the intrinsic connections between spatial-domain coded ptychography and Fourier ptychography. A step-by-step guide then provides the user instructions for developing both systems with practical examples. In the spatial-domain implementation, we explain how a large-scale, high-performance blood-cell lens can be made at negligible expense. In the Fourier-domain implementation, we explain how adding a low-cost light source to a regular microscope can improve the resolution beyond the limit of the objective lens. The turnkey operation of these setups is suitable for use by professional research laboratories, as well as citizen scientists. Users with basic experience in optics and programming can build the setups within a week. The do-it-yourself nature of the setups also allows these procedures to be implemented in laboratory courses related to Fourier optics, biomedical instrumentation, digital image processing, robotics and capstone projects.

Optical ptychography for biomedical imaging: recent progress and future directions [Invited].

Ptychography is an enabling microscopy technique for both fundamental and applied sciences. In the past decade, it has become an indispensable imaging tool in most X-ray synchrotrons and national laboratories worldwide. However, ptychography's limited resolution and throughput in the visible light regime have prevented its wide adoption in biomedical research. Recent developments in this technique have resolved these issues and offer turnkey solutions for high-throughput optical imaging with minimum hardware modifications. The demonstrated imaging throughput is now greater than that of a high-end whole slide scanner. In this review, we discuss the basic principle of ptychography and summarize the main milestones of its development. Different ptychographic implementations are categorized into four groups based on their lensless/lens-based configurations and coded-illumination/coded-detection operations. We also highlight the related biomedical applications, including digital pathology, drug screening, urinalysis, blood analysis, cytometric analysis, rare cell screening, cell culture monitoring, cell and tissue imaging in 2D and 3D, polarimetric analysis, among others. Ptychography for high-throughput optical imaging, currently in its early stages, will continue to improve in performance and expand in its applications. We conclude this review article by pointing out several directions for its future development.

Mixed cellulose ester membrane as an ion redistributor to stabilize zinc anode in aqueous zinc ion batteries.

Aqueous zinc-ion batteries (AZBs) with high energy density, low cost and environmental characteristics, have become the promising device for energy storage. However, uncontrolled zinc dendrite growth remains an impediment to the popularization of AZBs. The unrestricted two-dimensional (2D) ions diffusion is the main cause of the above defect. In this work, mixed cellulose ester (MCE) membrane is proposed as the separator. A dense homogeneous pore structure can achieve a physical shunting effect on ion diffusion, which can control and homogenize the ion motion. Further, the mechanism of this physical pore effect is confirmed by comparing the behavior of Zn deposition in MCE systems with different pore sizes but the same composition. As conjectured, a membrane with a smaller pore size is more favorable. In addition, the MCE contains many polar oxygen-containing functional groups that can facilitate and modulate ion diffusion through coordination. This chemical ion guiding effect, together with the above physical pore effect, gives the separator the ability to suppress dendrite formation. Zn/Zn symmetric cells with this membrane exhibit ultralong cycle life exceeding 1250 h at 0.5 mA cm-2 and 1000 h at 5 mA cm-2. And the Zn//MnO2 battery presents excellent cycle stability for more than 500 cycles with a capacity retention of 90.67%. This work proposes MCE separators and reveals their coordinated regulation of physical and chemical effects on metal-based anodes. This will shed light on the development of high-performance separators and AZBs.

Remote referencing strategy for high-resolution coded ptychographic imaging.

The applications of conventional ptychography are limited by its relatively low resolution and throughput in the visible light regime. The new development of coded ptychography (CP) has addressed these issues and achieved the highest numerical aperture for large-area optical imaging in a lensless configuration. A high-quality reconstruction of CP relies on precise tracking of the coded sensor's positional shifts. The coded layer on the sensor, however, prevents the use of cross correlation analysis for motion tracking. Here we derive and analyze the motion tracking model of CP. A novel, to the best of our knowledge, remote referencing scheme and its subsequent refinement pipeline are developed for blind image acquisition. By using this approach, we can suppress the correlation peak caused by the coded surface and recover the positional shifts with deep sub-pixel accuracy. In contrast with common positional refinement methods, the reported approach can be disentangled from the iterative phase retrieval process and is computationally efficient. It allows blind image acquisition without motion feedback from the scanning process. It also provides a robust and reliable solution for implementing ptychography with high imaging throughput. We validate this approach by performing high-resolution whole slide imaging of bio-specimens.

Depth-multiplexed ptychographic microscopy for high-throughput imaging of stacked bio-specimens on a chip.

Imaging a large number of bio-specimens at high speed is essential for many biomedical applications. The common strategy is to place specimens at different lateral positions and image them sequentially. Here we report a new on-chip imaging strategy, termed depth-multiplexed ptychographic microscopy (DPM), for parallel imaging and sensing at high speed. Different from the common strategy, DPM stacks multiple specimens in the axial direction and images the entire z-stack all at once. In our prototype platform, we modify a low-cost car mirror for programmable steering of the incident laser beam. A blood-coated image sensor is then placed underneath the stacked sample for acquiring the resulting diffraction patterns. With the captured images, we perform blind recovery of the incident beam angle and model different layers of the stacked sample as different coded surfaces for object reconstruction. For in vitro experiment, we demonstrate time-lapse cell culture monitoring by imaging 3 stacked microfluidic channels on the coded sensor. For high-throughput cytometric analysis, we image 5 stacked brain sections with a 205-mm2 field of view in ∼50 s. Cytometric analysis is also performed to quantify the cellular proliferation biomarkers on the slides. The DPM approach adds a new degree of freedom for data multiplexing in microscopy, enabling parallel imaging of multiple specimens using a single detector. The demonstrated 6-mm depth of field is among the longest ones in microscopy imaging. The novel depth-multiplexed configuration also complements the miniaturization provided by microfluidics devices, offering a solution for on-chip sensing and imaging with efficient sample handling.

Antithrombotic strategy in cancer patients comorbid with acute coronary syndrome and atrial fibrillation.

It has been shown that patients with cancer have a longer expected life duration, benefiting from advanced medical therapy. Meanwhile, the risk of suffering from cardiovascular disease (CVD) has been increasing with ageing. A growing number of studies have elucidated the association between cancer and CVD. Cancer, atrial fibrillation (AF) and coronary artery disease share some common factors and interact with each other, such as obesity, aging, diabetes, and inflammation, but the potential specific mechanism is still unclear. In addition, cancer-specific and therapy-related factors may increase the risk of embolism and bleeding in patients with cancer than in general population. However, current available embolic and bleeding risk scores applied in patients with CVD may not be applicable for risk assessment in cancer patients, which would be difficult for clinicians to select an appropriate antithrombotic regimen and ensure the balance between bleeding and embolism. Moreover, different types of cancer have distinct risks, which may increase the complexity of antithrombotic therapy. In this review, we review the literature related to cancer, AF, and acute coronary syndrome, focusing on the epidemiological status, physiological mechanism, embolism and bleeding risks, and strategies of antithrombotic therapy.

Effect of co-toxicity of lead and nanoplastics on the flavonoid biosynthetic pathway in dandelion (Taraxacum asiaticum Dahlst).

MAIN CONCLUSION: Negatively charged carboxy-polystyrene (CPS) and positively charged amino-polystyrene (NPS) could significantly inhibit the biomass and flavonoid content of dandelion roots and leaves, and the inhibitory effect of NPS was stronger than that of CPS. The increasingly serious pollution of microplastics and heavy metals is likely to affect the efficacy of flavonoids synthesized by dandelion in natural medicine fields. Therefore, we combined hydroponic experiments with computational chemistry (Gaussian and autodock analysis) to explore the mechanism by which amino-polystyrene (NPS), carboxy-polystyrene (CPS), and lead affect the flavonoid biosynthetic pathway in dandelion (Taraxacum asiaticum Dahlst). Our results show that CPS and NPS could significantly inhibit the biomass and flavonoid content of dandelion roots and leaves, and the inhibitory effect of NPS was stronger than that of CPS. Mechanistic studies showed that CPS and NPS increased the content of O2- and H2O2 in dandelion roots and leaves, causing membrane lipid peroxidation, resulting in cell damage and decreased biomass. CPS and NPS inhibited related enzymatic activities by affecting their tertiary structures, resulting in a decrease in phenolic acid, coumaroyl-CoA, and flavonoid content. Dandelion preferred to absorb positively charged NPS compared to negatively charged CPS, but CPS inhibited the uptake of Pb by dandelion more strongly than NPS. Pb promoted CPS agglomeration and increased the surface positive charge of CPS through coordination bonds and hydrogen bonds, so more CPS entered dandelion under CPS + Pb treatment than under CPS alone. Although NPS and CPS reduced the uptake of Pb by dandelion, the biomass and flavonoid contents of dandelion were lower than those of single Pb treatment because of the higher toxicity of NPS and CPS than Pb. Pb significantly increased the effect of CPS on the root biomass of dandelion compared with CPS alone by increasing the positive charge of CPS. We suggest that microplastics with different charges and lead composite pollution inhibit dandelion flavonoid biosynthesis and provide a reference for the loss of dandelion medicinal components and economic value.

High-throughput digital pathology via a handheld, multiplexed, and AI-powered ptychographic whole slide scanner.

The recent advent of whole slide imaging (WSI) systems has moved digital pathology closer to diagnostic applications and clinical practices. Integrating WSI with machine learning promises the growth of this field in upcoming years. Here we report the design and implementation of a handheld, colour-multiplexed, and AI-powered ptychographic whole slide scanner for digital pathology applications. This handheld scanner is built using low-cost and off-the-shelf components, including red, green, and blue laser diodes for sample illumination, a modified stage for programmable sample positioning, and a synchronized image sensor pair for data acquisition. We smear a monolayer of goat blood cells on the main sensor for high-resolution lensless coded ptychographic imaging. The synchronized secondary sensor acts as a non-contact encoder for precisely tracking the absolute object position for ptychographic reconstruction. For WSI, we introduce a new phase-contrast-based focus metric for post-acquisition autofocusing of both stained and unstained specimens. We show that the scanner can resolve the 388-nm linewidth on the resolution target and acquire gigapixel images with a 14 mm × 11 mm area in ∼70 seconds. The imaging performance is validated with regular stained pathology slides, unstained thyroid smears, and malaria-infected blood smears. The deep neural network developed in this study further enables high-throughput cytometric analysis using the recovered complex amplitude. The reported do-it-yourself scanner offers a portable solution to transform the high-end WSI system into one that can be made widely available at a low cost. The capability of high-throughput quantitative phase imaging may also find applications in rapid on-site evaluations.

Blood-Coated Sensor for High-Throughput Ptychographic Cytometry on a Blu-ray Disc.

The Blu-ray drive is an engineering masterpiece that integrates disc rotation, pickup head translation, and three lasers in a compact and portable format. Here, we integrate a blood-coated image sensor with a modified Blu-ray drive for high-throughput cytometric analysis of various biospecimens. In this device, samples are mounted on the rotating Blu-ray disc and illuminated by the built-in lasers from the pickup head. The resulting coherent diffraction patterns are then recorded by the blood-coated image sensor. The rich spatial features of the blood-cell monolayer help down-modulate the object information for sensor detection, thus forming a high-resolution computational biolens with a theoretically unlimited field of view. With the acquired data, we develop a lensless coherent diffraction imaging modality termed rotational ptychography for image reconstruction. We show that our device can resolve the 435 nm line width on the resolution target and has a field of view only limited by the size of the Blu-ray disc. To demonstrate its applications, we perform high-throughput urinalysis by locating disease-related calcium oxalate crystals over the entire microscope slide. We also quantify different types of cells on a blood smear with an acquisition speed of ∼10,000 cells per second. For in vitro experiments, we monitor live bacterial cultures over the entire Petri dish with single-cell resolution. Using biological cells as a computational lens could enable new intriguing imaging devices for point-of-care diagnostics. Modifying a Blu-ray drive with the blood-coated sensor further allows the spread of high-throughput optical microscopy from well-equipped laboratories to citizen scientists worldwide.

Recent advances in high- ß N experiments and magnetohydrodynamic instabilities with hybrid scenarios in the HL-2A Tokamak.

Over the past several years, high- ß N experiments have been carried out on HL-2A. The high- ß N is realized using double transport barriers (DTBs) with hybrid scenarios. A stationary high- ß N ( > 2 ) scenario was obtained by pure neutral-beam injection (NBI) heating. Transient high performance was also achieved, corresponding to ß N ≥ 3 , n e / n e G ∼ 0.6 , H 98 ∼ 1.5 , f b s ∼ 30 % , q 95 ∼ 4.0 , and G ∼ 0.4 . The high- ß N scenario was successfully modeled using integrated simulation codes, that is, the one modeling framework for integrated tasks (OMFIT). In high- ß N plasmas, magnetohydrodynamic (MHD) instabilities are abundant, including low-frequency global MHD oscillation with n = 1, high-frequency coherent mode (HCM) at the edge, and neoclassical tearing mode (NTM) and Alfvénic modes in the core. In some high- ß N discharges, it is observed that the NTMs with m / n = 3 / 2 limit the growth of the plasma energy and decrease ß N . The low-n global MHD oscillation is consistent with the coupling of destabilized internal (m/n = 1/1) and external (m/n = 3/1 or 4/1) modes, and plays a crucial role in triggering the onset of ELMs. Achieving high- ß N on HL-2A suggests that core-edge interplay is key to the plasma confinement enhancement mechanism. Experiments to enhance ß N will contribute to future plasma operation, such as international thermonuclear experimental reactor .

Quantitative multi-height phase retrieval via a coded image sensor.

Multi-height phase retrieval introduces different object-to-detector distances for obtaining phase diversity measurements. In the acquisition process, the slow-varying phase information, however, cannot be converted to intensity variations for detection. Therefore, the low-frequency contents of the phase profile are lost during acquisition and cannot be properly restored via phase retrieval. Here, we demonstrate the use of a coded image sensor for addressing this challenge in multi-height phase retrieval. In our scheme, we add a coded layer on top of the image sensor for encoding the slow-varying complex wavefronts into intensity variations of the modulated patterns. Inspired by the concept of blind ptychography, we report a reconstruction scheme to jointly recover the complex object and the unknown coded layer using multi-height measurements. With both simulation and experimental results, we show that the recovered phase is quantitative and the slow-varying phase profiles can be properly restored using lensless multi-height measurements. We also show that the image quality using the coded sensor is better than that of a regular image sensor. For demonstrations, we validate the reported scheme with various biospecimens and compare the results to those of regular lensless multi-height phase retrieval. The use of a coded image sensor may enable true quantitative phase imaging for the lensless multi-height, multi-wavelength, and transport-of-intensity equation approaches.

Optofluidic ptychography on a chip.

We report the implementation of a fully on-chip, lensless microscopy technique termed optofluidic ptychography. This imaging modality complements the miniaturization provided by microfluidics and allows the integration of ptychographic microscopy into various lab-on-a-chip devices. In our prototype, we place a microfluidic channel on the top surface of a coverslip and coat the bottom surface with a scattering layer. The channel and the coated coverslip substrate are then placed on top of an image sensor for diffraction data acquisition. Similar to the operation of a flow cytometer, the device utilizes microfluidic flow to deliver specimens across the channel. The diffracted light from the flowing objects is modulated by the scattering layer and recorded by the image sensor for ptychographic reconstruction, where high-resolution quantitative complex images are recovered from the diffraction measurements. By using an image sensor with a 1.85 µm pixel size, our device can resolve the 550 nm linewidth on the resolution target. We validate the device by imaging different types of biospecimens, including C. elegans, yeast cells, paramecium, and closterium sp. We also demonstrate a high-resolution ptychographic reconstruction at a video framerate of 30 frames per second. The reported technique can address a wide range of biomedical needs and engenders new ptychographic imaging innovations in a flow cytometer configuration.

Deep learning-enabled whole slide imaging (DeepWSI): oil-immersion quality using dry objectives, longer depth of field, higher system throughput, and better functionality.

Whole slide imaging (WSI) has moved the traditional manual slide inspection process to the era of digital pathology. A typical WSI system translates the sample to different positions and captures images using a high numerical aperture (NA) objective lens. Performing oil-immersion microscopy is a major obstacle for WSI as it requires careful liquid handling during the scanning process. Switching between dry objective and oil-immersion lens is often impossible as it disrupts the acquisition process. For a high-NA objective lens, the sub-micron depth of field also poses a challenge to acquiring in-focus images of samples with uneven topography. Additionally, it implies a small field of view for each tile, thus limiting the system throughput and resulting in a long acquisition time. Here we report a deep learning-enabled WSI platform, termed DeepWSI, to substantially improve the system performance and imaging throughput. With this platform, we show that images captured with a regular dry objective lens can be transformed into images comparable to that of a 1.4-NA oil immersion lens. Blurred images with defocus distance from -5 µm to +5 µm can be virtually refocused to the in-focus plane post measurement. We demonstrate an equivalent data throughput of >2 gigapixels per second, the highest among existing WSI systems. Using the same deep neural network, we also report a high-resolution virtual staining strategy and demonstrate it for Fourier ptychographic WSI. The DeepWSI platform may provide a turnkey solution for developing high-performance diagnostic tools for digital pathology.