Low-cost optical manipulation using hanging droplets of PDMS

We propose and demonstrate a low-cost optical micromanipulation system that makes use of simple microfrabricated components coupled to a smartphone camera for imaging. Layering hanging droplets of polydimethylsiloxane (PDMS) on microscope coverslips, and curing with a 100 W bulb, creates lenses capable of optical trapping. Optically trapped 3.93 μm silica beads were imaged with a second hanging droplet lens, doped with 1400 μg mL-1 Sudan II dye. Through doping, a lens with an integrated long-pass filter that effectively blocks the 532 nm trapping light was produced. Illumination was provided by shining a lamp into polystyrene foam packaging, perpendicular to the imaging path, producing a diffuse light source. We report trapping Q values of ~ 8.9 × 10-3. The techniques here are an addition to the growing body of work on low cost and adaptable microfluidics

Advances in automated tongue diagnosis techniques

This paper reviews the recent advances in a significant constituent of traditional oriental medicinal technology, called tongue diagnosis. Tongue diagnosis can be an effective, noninvasive method to perform an auxiliary diagnosis any time anywhere, which can support the global need in the primary healthcare system. This work explores the literature to evaluate the works done on the various aspects of computerized tongue diagnosis, namely preprocessing, tongue detection, segmentation, feature extraction, tongue analysis, especially in traditional Chinese medicine (TCM). In spite of huge volume of work done on automatic tongue diagnosis (ATD), there is a lack of adequate survey, especially to combine it with the current diagnosis trends. This paper studies the merits, capabilities, and associated research gaps in current works on ATD systems. After exploring the algorithms used in tongue diagnosis, the current trend and global requirements in health domain motivates us to propose a conceptual framework for the automated tongue diagnostic system on mobile enabled platform. This framework will be able to connect tongue diagnosis with the future point-of-care health system

Blood cancer care in a resource limited setting during the Covid-19 outbreak; a single center experience from Sri Lanka

BackgroundThe Covid-19 pandemic has caused significant morbidity and mortality among patients with cancer. Most countries employed measures to prevent spread of Covid-19 infection which include shielding, quarantine, lockdown, travel restrictions, physical distancing and the use of personal protective equipment. This study was carried out to assess the change in patient attendance and the efficacy of newly implemented strategies to mitigate the impact of Covid-19 on services at the Lanka Hospital Blood Cancer Centre (LHBCC) in Colombo, Sri Lanka.MethodologyTelephone consultation, infection control, personal protective measures and emergency admission policy were implemented with the aim of having a Covid-19 free ward and to prevent cross-infections. This descriptive cross-sectional study was conducted with 1399 patient episodes (in-patient care or day-case review). We analysed patients treated as in-patient as well as day-case basis between 01st April 2020 and 31st December 2020.ResultsThere were 977 day-case based episodes and 422 in-patient based episodes. There was a 14% drop in episode numbers compared to same period in 2019. There was no cross infection and no patients with Covid-19 related symptoms or positive test results entered the LHBCC during the study period.ConclusionServices in blood cancer care were maintained to prevent late stage presentation and adverse outcome. Measures implemented to prevent Covid-19 were effective to allow continuation of treatment. This study highlights the importance of implementing strict protocols, clinical screening, use of appropriate personal protective equipment in delivering blood cancer care during the Covid-19 pandemic. This is the only documented study relating to outcome and successful applicability of measures to prevent spread of Covid-19 infection and maintaining services among blood cancer patients in Sri Lanka

Response and Survival Estimates of Patients With Plasma Cell Myeloma in a Resource-Constrained Setting Using Protocols From High-Income Countries:A Single-Center Experience From Sri Lanka

There is a significant disparity in global cancer care and outcome between countries. Progress in the treatment of symptomatic plasma cell myeloma (PCM) in high-income countries is not seen in low- and middle-income countries. MATERIALS AND METHODS: This is was a retrospective cohort study of all patients diagnosed with PCM between May 1, 2013, and September 30, 2021, at the first hemato-oncology center in Sri Lanka. We aimed to provide data on clinicopathologic characteristics, response, and survival estimates. RESULTS: A total of 79 patients with PCM received first-line therapy during the study period. The median age was 64 years, and approximately one third (33%) of patients were older than 70 years. There were 42 (53%) males and 37 females. Hypercalcemia, renal impairment, anemia, and bone disease were detected in 36.7%, 38%, 72.1%, and 81%, respectively. Thirty-nine, 34, and six patients received a combination of cyclophosphamide, thalidomide, and dexamethasone; bortezomib, thalidomide, and dexamethasone; and other treatments, respectively. The overall response rate (≥ partial response) was approximately 97% for both cyclophosphamide, thalidomide, and dexamethasone and bortezomib, thalidomide, and dexamethasone. Twenty-three (29%) of these patients died during the study period, but only 14 (18%) died due to PCM or associated sepsis. After a median follow-up of 40.6 months (range, 35.2-59.07 months), the median overall survival was 84.2 months (95% CI, 60.87 to not available). The 5-year estimated overall survival was 65%. CONCLUSION: To our knowledge, this is the only well-characterized study on long-term survival of patients with PCM in Sri Lanka. We have shown that it is possible to successfully apply Western treatment and supportive care protocols to the local population. These published data will help to benchmark and improve the treatment and develop blood cancer care in the local setting

A lateral electrophoretic flow diagnostic assay

Immunochromatographic assays are a cornerstone tool in disease screening. To complement existing lateral flow assays (based on wicking flow) we introduce a lateral flow format that employs directed electrophoretic transport. The format is termed a “lateral e-flow assay” and is designed to support multiplexed detection using immobilized reaction volumes of capture antigen. To fabricate the lateral e-flow device, we employ mask-based UV photopatterning to selectively immobilize unmodified capture antigen along the microchannel in a barcode-like pattern. The channel-filling polyacrylamide hydrogel incorporates a photoactive moiety (benzophenone) to immobilize capture antigen to the hydrogel without a priori antigen modification. We report a heterogeneous sandwich assay using low-power electrophoresis to drive biospecimen through the capture antigen barcode. Fluorescence barcode readout is collected via a low-resource appropriate imaging system (CellScope). We characterize lateral e-flow assay performance and demonstrate a serum assay for antibodies to the hepatitis C virus (HCV). In a pilot study, the lateral e-flow assay positively identifies HCV+ human sera in 60 min. The lateral e-flow assay provides a flexible format for conducting multiplexed immunoassays relevant to confirmatory diagnosis in near-patient settings

Proteomic Analysis of Colorectal Cancer: Prefractionation Strategies Using two-Dimensional Free-Flow Electrophoresis

This review deals with the application of a new prefractionation tool, free-flow electrophoresis (FFE), for proteomic analysis of colorectal cancer (CRC). CRC is a leading cause of cancer death in the Western world. Early detection is the single most important factor influencing outcome of CRC patients. If identified while the disease is still localized, CRC is treatable. To improve outcomes for CRC patients there is a pressing need to identify biomarkers for early detection (diagnostic markers), prognosis (prognostic indicators), tumour responses (predictive markers) and disease recurrence (monitoring markers). Despite recent advances in the use of genomic analysis for risk assessment, in the area of biomarker identification genomic methods alone have yet to produce reliable candidate markers for CRC. For this reason, attention is being directed towards proteomics as a complementary analytical tool for biomarker identification. Here we describe a proteomics separation tool, which uses a combination of continuous FFE, a liquid-based isoelectric focusing technique, in the first dimension, followed by rapid reversed-phase HPLC (1–6 min/analysis) in the second dimension. We have optimized imaging software to present the FFE/RP-HPLC data in a virtual 2D gel-like format. The advantage of this liquid based fractionation system over traditional gel-based fractionation systems is the ability to fractionate large quantity protein samples. Unlike 2D gels, the method is applicable to both high-Mr proteins and small peptides, which are difficult to separate, and in the case of peptides, are not retained in standard 2D gels

Do All Patients Require Radiotherapy after Breast-Conserving Surgery?

Radiotherapy following breast conservation is routine in the treatment of breast cancer. This creates a large demand for radiotherapy services with implicit cost effects and potential morbidity to patients. Radiotherapy is administered to decrease local recurrence, but is radiotherapy required for all breast cancers? A literature search using the Medline and Ovid databases was conducted between 1965 and 2010 using the terms ‘role of radiotherapy’, ‘early breast cancer’, and omission of radiotherapy’. Papers with clinical trials published in English in adult humans were included. Fourteen randomized controlled trials were included. Local recurrence rates range from 0.8–35% in patients in whom radiotherapy was omitted. Low risk characteristics include older age, small tumor size, no lymphovascular invasion and low to moderate grade. At present, there is no clearly defined low risk group of patients in whom radiotherapy can be omitted

Global Health Diagnostics Utilizing Consumer Electronics: Development and Field Implementation

The global health implications of improper disease screening and diagnosis are tremendous, contributing to unnecessary disease burden and ongoing transmission of infectious diseases. While tools have been developed to help trained physicians and scientists diagnose disease in centralized healthcare facilities, many patients present with symptoms in resource-constrained settings. The limitations in infrastructure and skill present are often incompatible with existing diagnostic tools. The work in this dissertation centers on the engineering design, validation, and deployment of optical diagnostics targeted to these resource constraints. The approaches presented here take advantage of advances in mobile consumer electronics that have put high quality optics, automation, and data transmission capabilities into a compact and widely available package. In Chapter 1, I describe the limitations of current diagnostic tools for two diseases, oral cancer and tuberculosis, and outline the potential for development of novel tools around mobile devices. In Chapter 2, I present work that is a prerequisite for the rational design of reproducible and quantitative imaging with a mobile phone. Mobile phones and their cameras have seen rapid changes in specifications and performance, but they remain consumer devices with several corresponding limitations for medical use. I characterize the imaging capabilities of mobile phones across time as part of a custom portable microscope, detailing sampling limitations, aberrations, and the consequences of unwanted image processing. I conclude that mobile phones, through appropriate optical design and workflow management, can perform sufficiently for diagnostic imaging applications. In Chapter 3, I demonstrate a multi-color fluorescence imaging device based on a mobile phone for read-out of a sandwich immunoassay on a microfluidic chip. Microfluidic devices, systems that manipulate small volumes of liquid, have the potential to enable rapid and appropriate diagnostics at the point of care through reducing volume for patient samples and lowering cost. One of the limitations of microfluidic systems is that measuring the output of the device traditionally requires a large conventional microscope and scientific camera for visualization and quantification. Multi-color fluorescence on a mobile phone offers a powerful and portable alternative. Current diagnostics for tuberculosis, a disease that kills over 1 million people a year globally, have advanced dramatically in the recent decade, but the devices that detect the DNA of tuberculosis have not succeeded in extending testing capabilities to peripheral healthcare settings where they are most needed. New nucleic acid amplification tests are promising for this setting; they eliminate the need for cycling temperature and provide a more rapid time to answer. In Chapter 4, I demonstrate that it is possible to control and measure the amplification of DNA in real-time with this new class of assay using a mobile phone camera. Demonstration of this capability required development of an optical system, custom software, sample handling geometry, and thermal management. I also include initial validation of a primer set contributed by collaborators that is sensitive across a range of strains of tuberculosis. Ongoing work is focused on combining these capabilities into an integrated tuberculosis diagnostic. In Chapter 5, I present a field deployment of a diagnostic microscope for oral cancer built around a tablet computer. Oral cancer is the single largest cause of cancer mortality for men in India and other high burden countries. Cultural habits that increase the risk of developing oral cancer combine with delays in diagnosis leading to poor prognoses for patients. To improve the diagnostic process, it is important to screen patients early in the disease progression and refer them for a full diagnosis and care. In this work, I adapt both a manual microscope and automated slide-scanning device to the needs of oral cancer screening by brush biopsy. Through collaboration with clinical and corporate partners, these devices have been deployed and data collection has begun. I present initial images generated from patients and classified by pathologists that demonstrate the diagnostic workflow in practice. Affecting care in a global health setting is a complex challenge, but through work presented in this dissertation I contribute a combination of novel diagnostic method development, detailed device characterization, and field data collection that demonstrate the potential of global health diagnostics based on consumer electronics