Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. METHODS: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. RESULTS: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. CONCLUSION: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

The use of indocyanine green and near-infrared fluorescence imaging to assist sentinel lymph node biopsy in cutaneous melanoma: A systematic review.

BACKGROUND AND OBJECTIVES: Despite the use of blue dye and radioisotopes, sentinel lymph node biopsy (SLNB) is still associated with a high false-negative rate (FNR). The off-label use of indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging has been introduced with the objective of assisting SLNB and thereby improving regional control in melanoma. The objective of this study was to review and summarize the general experience, protocols and outcomes of the use of ICG and NIRF to assist SLNB in melanoma. METHODS: A systematic literature review was performed in December 2019 as per the PRISMA guidelines. Inclusion criteria were articles written in English describing the applications of ICG in patients with melanoma. Systematic reviews, animal studies, case reports and letters to editors were excluded. RESULTS: Of the 585 studies retrieved, 13 articles met the inclusion criteria. The reported sentinel lymph node (SLN) detection rate using ICG was between 86 and 100% of nodes identified by lymphoscintigraphy. The average number of nodes per patient detected using ICG was 2. ICG fluorescence imaging contributed to the identification of 2.0% of the total number of SLNs harvested. CONCLUSIONS: ICG fluorescence may be a useful adjunct to lymphoscintigraphy, although high-level comparative data is lacking. It was found to be superior to blue dye at detecting sentinel lymph nodes.

5-Aminolevulinic Acid Hydrochloride (5-ALA)-Guided Surgical Resection of High-Grade Gliomas: A Health Technology Assessment.

BACKGROUND: High-grade gliomas are a type of malignant brain tumour. Optimal management often includes maximal surgical resection. 5-aminolevulinic acid hydrochloride (5-ALA) is an imaging agent that makes a high-grade glioma fluoresce under blue light, which can help guide the surgeon when removing the tumour. We conducted a health technology assessment of 5-ALA-guided surgical resection of high-grade gliomas, which included an evaluation of effectiveness, safety, the budget impact of publicly funding 5-ALA, and patient preferences and values. METHODS: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews, and selected and reported results from one review that was recent, of high quality, and relevant to our research question. We complemented the identified systematic review with a literature search to identify randomized controlled trials published after the review. We reported the risk of bias of each included study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also performed a systematic economic literature search to identify economic studies that compared 5-ALA-guided surgical resection of high-grade gliomas with standard surgical care or other intraoperative imaging modalities. We did not conduct a primary economic evaluation due to lack of high-quality published clinical evidence evaluating 5-ALA-guided surgical resection. From the perspective of the Ontario Ministry of Health, we analyzed the 5-year budget impact of publicly funding 5-ALA-guided surgical resection for adults with newly diagnosed, primary, high-grade gliomas for which resection is considered feasible. To contextualize the potential value of 5-ALA, we spoke with someone who had experience with high-grade glioma, 5-ALA-guided resection, and standard surgical treatment. RESULTS: We included one systematic review reporting on a single randomized controlled trial in the clinical evidence review. 5-ALA increased the proportion of patients achieving complete tumour resection compared with standard care (relative risk of incomplete resection 0.55, 95% confidence interval 0.42-0.71; GRADE: Low). Evidence was uncertain for an effect on overall survival with 5-ALA (hazard ratio for death 0.82, 95% confidence interval 0.62-1.07; GRADE: Low), but there may be an improvement in 6-month progression-free survival (GRADE: Very low). Adverse events between groups was insufficiently reported, but appeared similar between groups for overall and neurological adverse events, with an observed increase in neurological deficits 48 hours after surgery with 5-ALA (GRADE: Very low). The economic literature search identified five studies that met our inclusion criteria because they evaluated the cost-effectiveness of 5-ALA-guided surgical resection as compared with surgery with a standard operating microscope under white light ("white-light microscopy"). Most of these studies found 5-ALA-guided surgical resection was cost-effective compared to white-light microscopy for high-grade gliomas. However, all studies derived clinical model inputs of the comparative safety and effectiveness parameters of 5-ALA from limited and low-quality evidence. Public funding of 5-ALA-guided surgical resection in Ontario over the next 5 years would result in a budget impact of about $930,000 in year 1 to about $1,765,000 in year 5, yielding a total budget impact of about $7,500,000 over this period. The one participant we interviewed had experience with high-grade glioma, standard surgical treatment, and 5-ALA-guided resection. The participant felt that 5-ALA-guided resection resulted in accurate tumour removal and also found it reassuring that 5-ALA could help the surgeon better visualize the tumour. CONCLUSIONS: 5-ALA-guided surgical resection appears to improve the extent of resection of high-grade gliomas compared with surgery using standard white-light microscopy (GRADE: Low). The evidence suggests 5-ALA-guided resection may improve overall survival; however, we cannot exclude the possibility of no effect (Grade: Low). 5-ALA may improve 6-month progression-free survival, although the results are highly uncertain (GRADE: Very low). There is an uncertain impact on overall or neurological adverse events (GRADE: Very low). We did not identify any economic studies conducted from the perspective of the Ontario or Canadian public health care payer. Of the studies that met our inclusion criteria, most found 5-ALA-guided surgical resection was cost-effective compared to white-light microscopy for high-grade gliomas. However, clinical model inputs for the comparative effectiveness and safety of 5-ALA were based on limited and low-quality evidence. We estimate that publicly funding 5-ALA-guided surgical resection in Ontario over the next 5 years would result in a total 5-year budget impact of about $7,500,000. For people diagnosed with high-grade gliomas, 5-ALA is seen positively as a useful imaging tool for brain tumour resection.

A fully integrated bacterial pathogen detection system based on count-on-a-cartridge platform for rapid, ultrasensitive, highly accurate and culture-free assay.

Rapid, sensitive and accurate point-of-care-testing (POCT) of bacterial load from a variety of samples can help prevent human infections caused by pathogenic bacteria and mitigate their spreading. However, there is an unmet demand for a POCT device that can detect extremely low concentrations of bacteria in raw samples. Herein, we introduce the 'count-on-a-cartridge' (COC) platform for quantitation of the food-borne pathogenic bacteria Staphylococcus aureus. The system comprised of magnetic concentrator, sensing cartridge and fluorescent image reader with a built-in counting algorithm facilitated fluorescent microscopic bacterial enumeration in user-convenient manner with high sensitivity and accuracy within a couple of hours. The analytical performance of this assay is comparable to that of a standard plate count. The COC assay shows a sensitivity of 92.9% and specificity of 100% performed according to global microbiological criteria for S. aureus which is acceptable below 100 CFU/g in the food matrix. This culture-independent, rapid, ultrasensitive and highly accurate COC assay has great potential for places where prompt bacteria surveillance is in high demand.

A rapid-response and ratiometric fluorescent probe for nitric oxide: From the mitochondria to the nucleus in live cells.

Nitric oxide (NO) is a very important signal molecule implicated in numerous physiological and pathological processes, and its detection is the key to understand these processes. For this reason, various fluorescent probes have been developed for detection analysis of NO. However, few rapid-response (<1 min) and ratiometric fluorescent probe are reported for real-time detection of short-time NO in biological systems. In this work, we report a rapid-response (within several seconds) and ratiometric fluorescent probe, RatioTr, which displays selective and sensitive detection of NO in solutions, and detections of exo- and endogenous NO in live RAW 264.7 cells. Unexpectedly, the probe RatioTr and its sensing product (p-Nus) display different cellular localizations, the mitochondria and the nucleus, which were demonstrated by co-stained experiments. The sensing process of RatioTr toward NO from mitochondria to nucleus was observed in live cells by confocal fluorescence images. Furthermore, the subcellular localizations were demonstrated by measurements of pKa and interaction of p-Nus and DNA. In the presence of a natural DNA, calf thymus DNA, RatioTr is more sensitive to NO (LOD = 2.8 nM). Therefore, due to the nucleus localization together with a high fluorescence efficiency in the nucleus, p-Nus is a good candidate of cell-permeant nucleic acid stain or a fluorescent probe for the nucleus.

Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis.

BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.

Rapid cancer diagnosis by highly fluorescent carbon nanodots-based imaging.

Carbon dots (Cdots) with bright green fluorescence were applied to the rapid and selective cell imaging for a variety of cell lines. Different labeling distributions of hepatoma cells (HepG2) and normal human liver cells (LO2) were achieved using Cdots as imaging agents. For HepG2 cells, the Cdots could rapidly permeate the cell membrane and diffuse into the cytoplasm and nucleus within 3 min, and retained their location in the targets for 24 h. However, the Cdots exhibited bright fluorescence only in the cytoplasm of LO2 cell lines. Moreover, the Cdots were almost non-cytotoxic and exhibited superior photostability over a wide range of pH. Therefore, these Cdots have great potential for rapid, luminous and selective bioimaging applications, and are expected to be used as a nucleus-staining agent in cancer diagnosis. Graphical abstract ᅟ.

Portable, low-cost multispectral imaging system: design, development, validation, and utilization.

Optical spectral images can be used to estimate the amount of bulk absorbers in tissues, specifically oxy- and deoxyhemoglobin, as well as scattering parameters. Most systems that capture spectral image data are large, heavy, and expensive. This paper presents a full end-to-end analysis of a low-cost reflectance-mode multispectral imaging system operating in the visible and near-infrared spectra. The system consists of 13 LEDs mounted on a printed circuit board, a monochrome machine vision camera, and a tablet computer to control the hardware. The bill of materials for the system is less than $1000. Hardware design and implementation are detailed. Calibration, image capture, and preprocessing are also discussed. In validation experiments, excellent agreement is observed in diffuse reflectance measurements between the spectral camera setup and a spectrometer. To demonstrate that such spectral image data can yield meaningful optical measurements in vivo, the forearms of eight volunteers are imaged in the system. Their data are then analyzed to estimate the tissue optical properties of different skin layers using a Monte Carlo lookup table. In three volunteers, spectral images are captured before and after inducing erythema using a warm wet towel. Across the three subjects, a clear increase in the blood content of the superficial plexus layer was observed as a result of the erythema. Collectively, these findings suggest that a low-cost system can capture accurate spectral data and that clinically meaningful information can be derived from it.

Indocyanine green-based fluorescence imaging in visceral and hepatobiliary and pancreatic surgery: State of the art and future directions.

In recent years, the use of fluorescence-guided surgery (FGS) to treat benign and malignant visceral, hepatobiliary and pancreatic neoplasms has significantly increased. FGS relies on the fluorescence signal emitted by injected substances (fluorophores) after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible. This review surveys and discusses the most common and emerging clinical applications of indocyanine green (ICG)-based fluorescence in visceral, hepatobiliary and pancreatic surgery. The analysis, findings, and discussion presented here rely on the authors' significant experience with this technique in their medical institutions, an up-to-date review of the most relevant articles published on this topic between 2014 and 2018, and lengthy discussions with key opinion leaders in the field during recent conferences and congresses. For each application, the benefits and limitations of this technique, as well as applicable future directions, are described. The imaging of fluorescence emitted by ICG is a simple, fast, relatively inexpensive, and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems. The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future. Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.

Costs and effects of intra-operative fluorescence molecular imaging - A model-based, early assessment.

INTRODUCTION: Successful breast conserving cancer surgeries come along with tumor free resection margins and account for cosmetic outcome. Positive margins increase the likelihood of tumor recurrence. Intra-operative fluorescence molecular imaging (IFMI) aims to focus surgery on malignant tissue thus substantially lowering the presence of positive margins as compared with standard techniques of breast conservation (ST). A goal of this paper is to assess the incremental number of surgeries and costs of IFMI vs. ST. METHODS: We developed a decision analytical model and applied it for an early evaluation approach. Given uncertainty we considered that IFMI might reduce the proportion of positive margins found by ST from all to none and this proportion is assumed to be reduced to 10% for the base case. Inputs included data from the literature and a range of effect estimates. For the costs of IFMI, respective cost components were added to those of ST. RESULTS: The base case reduction lowered number of surgeries (mean [95% confidence interval]) by 0.22 [0.15; 0.30] and changed costs (mean [95% confidence interval]) by €-663 [€-1,584; €50]. A tornado diagram identified the Diagnosis Related Group (DRG) costs, the proportion of positive margins of ST, the staff time saving factor and the duration of frozen section analysis (FSA) as important determinants of this cost. CONCLUSIONS: These early results indicate that IFMI may be more effective than ST and through the reduction of positive margins it is possible to save follow-up surgeries-indicating further health risk-and to save costs through this margin reduction and the avoidance of FSA.

A rapid and nondestructive protocol for whole-mount bone staining of small fish and Xenopus.

Here we propose a new protocol for whole-mount bone staining, which allows the rapid preparation of highly cleared and nondestructive specimens. It only takes 3 days to complete whole procedure for small vertebrates, such as medaka, zebrafish, and Xenopus frogs. In this procedure, we used a newly developed fixative containing formalin, Triton X-100, and potassium hydroxide, which allows the fixation, decolorization, and transparentization of specimens at the same time. A bone staining solution containing alizarin red S with ethylene glycol and a clearing solution containing Tween 20 and potassium hydroxide also contributed the specificity and swiftness of this new system. As expected, although details of the skeletal system could be observed in specimens with high transparency, it was noteworthy that high-resolution fluorescence images acquired using zoom microscopes clearly delineated the shape of each bone. This new procedure would be expected to be widely used as a standard procedure for bone staining in the testing the developmental toxicity of chemicals and in the screening test of knockout or mutant animals.

Simple and inexpensive micromachined aluminum microfluidic devices for acoustic focusing of particles and cells.

We introduce a new method to construct microfluidic devices especially useful for bulk acoustic wave (BAW)-based manipulation of cells and microparticles. To obtain efficient acoustic focusing, BAW devices require materials that have high acoustic impedance mismatch relative to the medium in which the cells/microparticles are suspended and materials with a high-quality factor. To date, silicon and glass have been the materials of choice for BAW-based acoustofluidic channel fabrication. Silicon- and glass-based fabrication is typically performed in clean room facilities, generates hazardous waste, and can take several hours to complete the microfabrication. To address some of the drawbacks in fabricating conventional BAW devices, we explored a new approach by micromachining microfluidic channels in aluminum substrates. Additionally, we demonstrate plasma bonding of poly(dimethylsiloxane) (PDMS) onto micromachined aluminum substrates. Our goal was to achieve an approach that is both low cost and effective in BAW applications. To this end, we micromachined aluminum 6061 plates and enclosed the systems with a thin PDMS cover layer. These aluminum/PDMS hybrid microfluidic devices use inexpensive materials and are simply constructed outside a clean room environment. Moreover, these devices demonstrate effectiveness in BAW applications as demonstrated by efficient acoustic focusing of polystyrene microspheres, bovine red blood cells, and Jurkat cells and the generation of multiple focused streams in flow-through systems. Graphical abstract The aluminum acoustofluidic device and the generation of multinode focusing of particles.

A near-infrared fluorescent sensor with large Stokes shift for rapid and highly selective detection of thiophenols in water samples and living cells.

The development of simple methods with high sensitivity and selectivity to differentiate toxic aromatic thiols (thiophenols) from aliphatic thiols (cysteine, homocysteine, and glutathione) and hydrogen sulfide (H2S) is of great significance. Herein, we report on the fabrication of a novel near-infrared (NIR) fluorescent sensor for rapid and highly selective detection of thiophenols through the photoinduced electron transfer (PET) mechanism. In the presence of the thiophenols, an obvious enhancement of NIR fluorescence at 658 nm could be visualized with the aid of nucleophilic aromatic substitution (SNAr) reaction. The sensor displays large Stokes shift (~ 227 nm), fast response time (< 30 s), high sensitivity (~ 8.3 nM), and good biocompatibility. Moreover, the as-prepared sensor possesses an excellent anti-interference feature even when other possible interferents exist (aliphatic thiols and H2S) and has been successfully utilized for thiophenol detection in both water samples and living cells. Graphical abstract Illustration of the sensor for thiophenol imaging in living cells.

A low-cost microwell device for high-resolution imaging of neurite outgrowth in 3D.

OBJECTIVE: Current neuronal cell culture is mostly performed on two-dimensional (2D) surfaces, which lack many of the important features of the native environment of neurons, including topographical cues, deformable extracellular matrix, and spatial isotropy or anisotropy in three dimensions. Although three-dimensional (3D) cell culture systems provide a more physiologically relevant environment than 2D systems, their popularity is greatly hampered by the lack of easy-to-make-and-use devices. We aim to develop a widely applicable 3D culture procedure to facilitate the transition of neuronal cultures from 2D to 3D. APPROACH: We made a simple microwell device for 3D neuronal cell culture that is inexpensive, easy to assemble, and fully compatible with commonly used imaging techniques, including super-resolution microscopy. MAIN RESULTS: We developed a novel gel mixture to support 3D neurite regeneration of Aplysia bag cell neurons, a system that has been extensively used for quantitative analysis of growth cone dynamics in 2D. We found that the morphology and growth pattern of bag cell growth cones in 3D culture closely resemble the ones of growth cones observed in vivo. We demonstrated the capability of our device for high-resolution imaging of cytoskeletal and signaling proteins as well as organelles. SIGNIFICANCE: Neuronal cell culture has been a valuable tool for neuroscientists to study the behavior of neurons in a controlled environment. Compared to 2D, neurons cultured in 3D retain the majority of their native characteristics, while offering higher accessibility, control, and repeatability. We expect that our microwell device will facilitate a wider adoption of 3D neuronal cultures to study the mechanisms of neurite regeneration.

Using outcomes data to justify instituting new technology: a single institution's experience.

BACKGROUND: The PILLAR II trial demonstrated PINPOINT is safe, feasible to use with no reported adverse events and resulted in no anastomotic leaks in patients who had a change in surgical plan based on PINPOINT's intraoperative assessment of tissue perfusion during colorectal resection. Whether the cost savings associated with this reduction in anastomotic complications can offset the cost of investing in PINPOINT is unknown. METHODS: We performed a retrospective analysis of all patients (N = 347) undergoing colectomy with primary anastomosis from January 2015 to April 2016. These patients were stratified based on whether fluorescence imaging was used intraoperatively. The clinical outcomes of these patients were then evaluated based on their development of an anastomotic leak or stricture. The direct hospital costs per case were then calculated, and the economic impact of using fluorescence imaging was examined to assess whether decreased direct costs would justify the initial expenditures to purchase new technology (PINPOINT System, NOVADAQ, Canada). RESULTS: Fluorescence imaging in colorectal surgery using PINPOINT reduced the anastomotic failure rate in patients who underwent colon resection. The PINPOINT group (n = 238) had two (0.84%) anastomotic failures, while the non-PINPOINT group (n = 109) had six (5.5%) anastomotic failures. In the PINPOINT group, 11 (4.6%) patients had a change in the resection margin based on the results of the fluorescence imaging, and none of these patients experienced an anastomotic failure. Cost per case was less in the PINPOINT group secondary to fewer direct costs associated with complications. CONCLUSIONS: These results validate the findings of the PILLAR II trial and confirm the decrease in direct costs due to reduction in anastomotic failures as a result of using PINPOINT justified the expense of the new technology after just 143 cases.

Lensless imaging through multiple phase patterns illumination.

A stable optical system is required to acquire a high-quality image. A motionless lensless setup is designated to obtain high-resolution and large field of view images. The sample is sequentially illuminated with multiple random phase patterns, and the recorded images are subtracted from the system calibration images correspondingly. The resultant images are propagated to the sample plane. The summation of all images yields a final image with resolution of ∼4 µm, field of view of ∼15 mm2, and better signal-to-noise ratio. This technique provides a compact, stable, and cost-effective optical system.

A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage.

Various techniques have been developed to study changes in the cerebral vasculature in numerous neuropathological processes including subarachnoid hemorrhage (SAH). One of the most widely employed techniques uses India ink-gelatin casting, which presents numerous challenges due to its high viscosity, rapid solidification, and its impact on immunohistochemical analysis. To overcome these limitations, we developed a novel technique for assessing cerebral vasospasm using cerebrovascular perfusion with ROX, SE (5-Carboxy-X-Rhodamine, Succinimidyl Ester), a fluorescent labeling dye. We found that ROX SE perfusion achieves excellent delineation of the cerebral vasculature, was qualitatively and quantitatively superior to India ink-gelatin casting for the assessment of cerebral vasospasm, permits outstanding immunohistochemical examination of non-vasospasm components of secondary brain injury, and is a more efficient and cost-effective experimental technique. ROX SE perfusion is therefore a novel and highly useful technique for studying cerebrovascular pathology following experimental SAH.

An on-chip instrument for white blood cells classification based on a lens-less shadow imaging technique.

Routine blood tests provide important basic information for disease diagnoses. The proportions of three subtypes of white blood cells (WBCs), which are neutrophils, monocytes, lymphocytes, is key information for disease diagnosis. However, current instruments for routine blood tests, such as blood cell analyzers, flow cytometers, and optical microscopes, are cumbersome, time consuming and expensive. To make a smaller, automatic low-cost blood cell analyzer, much research has focused on a technique called lens-less shadow imaging, which can obtain microscopic images of cells in a lens-less system. Nevertheless, the efficiency of this imaging system is not satisfactory because of two problems: low resolution and imaging diffraction phenomena. In this paper, a novel method of classifying cells with the shadow imaging technique was proposed. It could be used for the classification of the three subtypes of WBCs, and the correlation of the results of classification between the proposed system and the reference system (BC-5180, Mindray) was 0.93. However, the instrument was only 10 × 10 × 10 cm, and the cost was less than $100. Depending on the lens-free shadow imaging technology, the main hardware could be integrated on a chip scale and could be called an on-chip instrument.

Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models.

Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model.

Ultra-portable, wireless smartphone spectrometer for rapid, non-destructive testing of fruit ripeness.

We demonstrate a smartphone based spectrometer design that is standalone and supported on a wireless platform. The device is inherently low-cost and the power consumption is minimal making it portable to carry out a range of studies in the field. All essential components of the device like the light source, spectrometer, filters, microcontroller and wireless circuits have been assembled in a housing of dimensions 88 mm × 37 mm × 22 mm and the entire device weighs 48 g. The resolution of the spectrometer is 15 nm, delivering accurate and repeatable measurements. The device has a dedicated app interface on the smartphone to communicate, receive, plot and analyze spectral data. The performance of the smartphone spectrometer is comparable to existing bench-top spectrometers in terms of stability and wavelength resolution. Validations of the device were carried out by demonstrating non-destructive ripeness testing in fruit samples. Ultra-Violet (UV) fluorescence from Chlorophyll present in the skin was measured across various apple varieties during the ripening process and correlated with destructive firmness tests. A satisfactory agreement was observed between ripeness and fluorescence signals. This demonstration is a step towards possible consumer, bio-sensing and diagnostic applications that can be carried out in a rapid manner.