Sub-pixel resolving optofluidic microscope for on-chip cell imaging

We report the implementation of a fully on-chip, lensless, sub-pixel resolving optofluidic microscope (SROFM). The device utilizes microfluidic flow to deliver specimens directly across a complementary metal oxide semiconductor (CMOS) sensor to generate a sequence of low-resolution (LR) projection images, where resolution is limited by the sensor's pixel size. This image sequence is then processed with a pixel super-resolution algorithm to reconstruct a single high resolution (HR) image, where features beyond the Nyquist rate of the LR images are resolved. We demonstrate the device's capabilities by imaging microspheres, protist Euglena gracilis, and Entamoeba invadens cysts with sub-cellular resolution and establish that our prototype has a resolution limit of 0.75 microns. Furthermore, we also apply the same pixel super-resolution algorithm to reconstruct HR videos in which the dynamic interaction between the fluid and the sample, including the in-plane and out-of-plane rotation of the sample within the flow, can be monitored in high resolution. We believe that the powerful combination of both the pixel super-resolution and optofluidic microscopy techniques within our SROFM is a significant step forwards toward a simple, cost-effective, high throughput and highly compact imaging solution for biomedical and bioscience needs

A smartphone-based chip-scale microscope using ambient illumination

Portable chip-scale microscopy devices can potentially address various imaging needs in mobile healthcare and environmental monitoring. Here, we demonstrate the adaptation of a smartphone's camera to function as a compact lensless microscope. Unlike other chip-scale microscopy schemes, this method uses ambient illumination as its light source and does not require the incorporation of a dedicated light source. The method is based on the shadow imaging technique where the sample is placed on the surface of the image sensor, which captures direct shadow images under illumination. To improve the image resolution beyond the pixel size, we perform pixel super-resolution reconstruction with multiple images at different angles of illumination, which are captured while the user is manually tilting the device around any ambient light source, such as the sun or a lamp. The lensless imaging scheme allows for sub-micron resolution imaging over an ultra-wide field-of-view (FOV). Image acquisition and reconstruction are performed on the device using a custom-built Android application, constructing a stand-alone imaging device for field applications. We discuss the construction of the device using a commercial smartphone and demonstrate the imaging capabilities of our system

Effect of lipid peroxidation products on the activity of human retinol dehydrogenase 12 (RDH12) and retinoid metabolism

AbstractMutations in human Retinol Dehydrogenase 12 (RDH12) are known to cause photoreceptor cell death but the physiological function of RDH12 in photoreceptors remains poorly understood. In vitro, RDH12 recognizes both retinoids and medium-chain aldehydes as substrates. Our previous study suggested that RDH12 protects cells against toxic levels of retinaldehyde and retinoic acid [S.A. Lee, O.V. Belyaeva, I.K. Popov, N.Y. Kedishvili, Overproduction of bioactive retinoic acid in cells expressing disease-associated mutants of retinol dehydrogenase 12, J. Biol. Chem. 282 (2007) 35621–35628]. Here, we investigated whether RDH12 can also protect cells against highly reactive medium-chain aldehydes. Analysis of cell survival demonstrated that RDH12 was protective against nonanal but not against 4-hydroxynonenal. At high concentrations, nonanal inhibited the activity of RDH12 towards retinaldehyde, suggesting that nonanal was metabolized by RDH12. 4-Hydroxynonenal did not inhibit the RDH12 retinaldehyde reductase activity, but it strongly inhibited the activities of lecithin:retinol acyl transferase and aldehyde dehydrogenase, resulting in decreased levels of retinyl esters and retinoic acid and accumulation of unesterified retinol. Thus, the results of this study showed that RDH12 is more effective in protection against retinaldehyde than against medium-chain aldehydes, and that medium-chain aldehydes, especially 4-hydroxynonenal, severely disrupt cellular retinoid homeostasis. Together, these findings provide a new insight into the effects of lipid peroxidation products and the impact of oxidative stress on retinoid metabolism

A Survey on the Impact of Operation Volume on Rectal Cancer Management

The rectal cancer management can be influenced by the surgeon's practice and the hospital. This study was to evaluate the differences according to the surgeon's operative volume and the level of the hospital. Questionnaires were sent out to the members of the 'Korean Society of Coloproctology', and the responses were evaluated according to the surgeon's operation volume, the surgeon's age, and the level of the hospital. Sixty responses were received during the three months' period (from August to October 2004). Thirty three respondents (55%) operated more than 50 cases of rectal cancer per year (high-volume surgeons), and 37 respondents (61%) worked at university hospitals or tertiary care facilities (high-level hospitals). The preoperative evaluation with endorectal ultrasonography (ERUS) was significantly different according to the surgeon's operation volume and the level of the hospital, whereas magnetic resonance imaging and positron emission tomography (PET) was significantly different only for the surgeon's operation volume. The preoperative radiation therapy was significantly different according to the surgeon's operation volume, the surgeon's age, and the level of the hospital. However, there was no significant difference found on the operative procedures or postoperative surveillance. The preoperative loco-regional evaluation and the preoperative radiation therapy could be considered as the factors that influence the volume-outcome relationship in rectal cancer treatment

On-chip continuous monitoring of motile microorganisms on an ePetri platform

Self-imaging Petri dish platforms with microscopy resolution, which we term ‘ePetri’, can significantly streamline cell cultures and/or other longitudinal biological studies. In this paper, we demonstrate high-resolution imaging and long-term culture of motile microorganisms in a specialized ePetri platform by taking advantage of the inherent motion. By applying a super-resolution algorithm to a set of low-resolution images of the microorganisms as they move across the sensing area of a complementary metal oxide semiconductor (CMOS) image sensor chip, we can render an improved-resolution image of the microorganisms. We perform a longitudinal study of Euglena gracilis cultured in an ePetri platform, and image-based analysis on the motion and morphology of the cells. As a miniaturized and automated culture monitoring platform, this ePetri technology can greatly improve studies and experiments with motile microorganisms

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

PURPOSE: Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer. MATERIALS AND METHODS: A total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls. RESULTS: Interpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma. CONCLUSION: Our study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.ope

Endoplasmic reticulum stress and apoptosis induced by manganese trigger α-synuclein accumulation

Purpose: To explore whether α-synuclein aggregation is linked to endoplasmic reticulum (ER) stress and apoptosis induced by manganese (Mn) on CATH.a dopaminergic cell lines.Methods: Western blot analysis for the expression of 78 kDa glucose-regulated protein (GRP78), phosphorylated eukaryotic initiation factor 2α (p-eIF-2α), eIF2α, inositol requiring enzyme 1(IRE-1α), cleaved caspase-3, and C/EBP homologous protein (CHOP) was performed, including overexpression of recombinant adenovirus-mediated α-synuclein on CATH.a dopaminergic cell line.Results: It was observed that cell viability (p < 0.05) was significantly reduced by 250 μM exposed for 3h and 1,000 μM of MnCl2 exposed for 24 h. The expression of p-elF-2α, IRE-1α, and GRP78 was especially induced by 1,000 μM of MnCl2 exposed at 3, 6, and 12 h, respectively (p < 0.05). Twenty four-hour exposure of 250 uM of MnCl2 and the 3 h exposure of 1,000 uM of MnCl2 significantly induced CHOP, active caspase 3 and α-synuclein expression (p < 0.05). α-Synuclein combined with recombinant adenoviral transduction increased GRP78, IRE-1α and eIF2a, CHOP and caspase 3 expression at longer times and at higher concentrations of manganese exposure on CATH.a dopaminergic cells.Conclusion: Based on these findings, Mn is a risk factor for diseases associated with α-synuclein accumulation. Furthermore, α-synuclein accumulation is associated with apoptosis via ER stress induced by Mn.Keywords: Manganese (Mn), α- Synuclein, Endoplasmic reticulum (ER) stress, Apoptosi

Parent-Reported Symptoms of Attention Deficit Hyperactivity Disorder in Children with Intermittent Exotropia before and after Strabismus Surgery

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens