Portable Diagnostic Devices Research Articles

Sleep and Pathological Wakefulness at the Time of Liberation from Mechanical Ventilation (SLEEWE). A Prospective Multicenter Physiological Study

Rationale: Abnormal patterns of sleep and wakefulness exist in mechanically ventilated patients. Objectives: In this study (SLEEWE [Effect of Sleep Disruption on the Outcome of Weaning from Mechanical Ventilation]), we aimed to investigate polysomnographic indexes as well as a continuous index for evaluating sleep depth, the odds ratio product (ORP), to determine whether abnormal sleep or wakefulness is associated with the outcome of spontaneous breathing trials (SBTs). Methods: Mechanically ventilated patients from three sites were enrolled if an SBT was planned the following day. EEG was recorded using a portable sleep diagnostic device 15 hours before the SBT. The ORP was calculated from the power of four EEG frequency bands relative to each other, ranging from full wakefulness (2.5) to deep sleep (0). The correlation between the right and left hemispheres' ORP (R/L ORP) was calculated. Measurements and Main Results: Among 44 patients enrolled, 37 had technically adequate signals: 11 (30%) passed the SBT and were extubated, 8 (21%) passed the SBT but were not deemed to be clinically ready for extubation, and 18 (49%) failed the SBT. Pathological wakefulness or atypical sleep were highly prevalent, but the distribution of classical sleep stages was similar between groups. The mean ORP and the proportion of time in which the ORP was >2.2 were higher in extubated patients compared with the other groups (P < 0.05). R/L ORP was significantly lower in patients who failed the SBT, and the area under the receiver operating characteristic curve of R/L ORP to predict failure was 0.91 (95% confidence interval, 0.75-0.98). Conclusions: Patients who pass an SBT and are extubated reach higher levels of wakefulness as indicated by the ORP, suggesting abnormal wakefulness in others. The hemispheric ORP correlation is much poorer in patients who fail an SBT.

Designing a mobile cardiac monitor

The mortality associated with cardiovascular diseases is increasing every year. Especially high its risk levels in the Arctic and the High North areas. It is necessary to continuously monitor cardiovascular patients in order to prevent sudden death among them. The development of a portable diagnostic monitoring device is what is seen as able to contribute to this task. We have developed a prototype of the device and tested it. The device is portable. It can transmit data to a computer. The data is recorded continuously, indicating the beginning of the crisis and its course. The device can be connected to a smartphone to send emergency signals to health care facility. The signal is sent automatically and carries information about the location of the patient and their condition, allowing doctors to provide services in timely manner.

Gut flora “the second brain” connects Eastern and Western medicine: intestinal hyper-permeability or Qi deficiency can affect brain, mind, and whole body

There are two famous “the Father of Modern Medicine”—Hippocrates (a Greek physician) said “all disease begins in the gut” and Sir William Osler (a Canadian physician) said “a man is as old as his arteries.” It is known that gut microbiota imbalance (dysbiosis) and intestinal hyper-permeability are related to high level of advanced glycation end-products (AGEs) which damage blood vessel’s endothelial function and potentially cause multi-organ dysfunction. On the other hand, Traditional Chinese Medicine (TCM) doctors already knew the importance of digestive system thousands of years ago since the production of “Qi” which is vital energy for whole body largely rely on abdominal condition, and Qi deficiency triggers multiple mental and physical symptoms. It may sound two leading Integrative Medicine (IM) systems, Western IM and TCM use “different languages,” but it is not well known that their essence is very similar (illness is a result of “dis-ease” or “dysfunction of Qi.”). Genome analysis technology, such as DNA sequencing and microbiota researches have enabled us to understand how intestinal dysbiosis is related to obesity, metabolic syndrome, brain disorders, autoimmune diseases, or mood disorders (Brain-Mind-Gut axis). In addition, making the most of artificial intelligence’s (AI) “deep learning” technology might be a potential “prescription” to heal worldwide medical-economical crisis, spend more time with patients (for medical providers), and prevent providers’ burnout. AI-assisted TCM-style history taking computer and portable wrist pulse diagnostic device are about to be used in China. In the new era of preventive medicine, gut microbiota research, precision medicine with genome analysis, AI technology and TCM ancient wisdom can be combined together. Blending the new and the old will make it possible to detect and treat “pre-clinical disease” before real diseases happen since Western IM and TCM are actually using a “same language.”

A portable nucleic acid detection system using natural convection combined with a smartphone

The development of portable nucleic acid diagnostic devices has the potential to expand the availability of molecular diagnostics into low-resource settings. One of the promising solutions for rapid and simple DNA amplification is the use of Rayleigh–Bernard natural convection which is caused by a buoyancy-driven thermal gradient of liquid when heated from below. This natural convection avoids the use of the complex and sophisticated hardware that is required for precise maintenance of temperature cycles in conventional PCR. We have developed a stand-alone convective PCR (cPCR) device linked to a smartphone for rapid detection of nucleic acids using natural convection heating. The device amplifies multiple DNA samples simultaneously using a custom-made heat block controlled by Bluetooth wireless communication. The entire device is highly portable, user-friendly, battery-operated and can provide target DNA amplification in less than 30 min. A detection limit of 2.8 × 103 copies of a segment of lambda DNA was obtained when the two different fluorescently-tagged amplicons were collected magnetically and detected using the smartphone fluorescence reader. Thus, the combination of cPCR and multiplex fluorescence-based detection on a smartphone provides new opportunities for the development of affordable and portable molecular diagnostic devices for point-of-care situations or remote clinical settings.

Integrating a Microwave Resonator and a Microchannel with an Immunochromatographic Strip for Stable and Quantitative Biodetection.

An immunochromatographic strip is an effective diagnostic tool in various fields because of its simplicity, rapidity, and cost-effectiveness. However, typical strips for preliminary screening provide only qualitative or semiquantitative results, and common solutions for quantitative detection by incorporating different kinds of nanoparticles as biomarkers still do not solve this problem thoroughly. Here, we try to tackle this challenge by integrating low-cost membrane-compatible square split-ring resonators and structure-design-flexible microchannels with flexible strips. We experimentally demonstrate that the limit of detection (LOD) and sensitivity of the strip for quantitative detection of Staphylococcus aureus reach 0.784 ng/mL and 10.214 MHz/(ng/mL), respectively. The LOD level is about 63 times higher than that of the color-based strip determined by the naked eye, and the stability is about 18 times higher than that of the fluorescent strip. This work could not only provide a powerful diagnosis tool for the quantitative detection of S. aureus or other molecules but also deliver new avenues for achieving electric field detection of biomolecules, system-level integration of biosensors, and the development of portable diagnostic devices.

Easy Diagnosis of Jaundice: A Smartphone-Based Nanosensor Bioplatform Using Photoluminescent Bacterial Nanopaper for Point-of-Care Diagnosis of Hyperbilirubinemia.

One of the concerns of parents in the first days of their baby's birth is the baby's risk of jaundice/hyperbilirubinemia. This is because more than 60% of babies are born with jaundice that, if not timely diagnosed and subsequently treated, can lead to serious damage to their health. On the other hand, despite recent progress in sensor technology for clinical applications, the development of easy-to-use, cost-effective, sensitive, specific, and portable diagnostic devices, which use nontoxic and biodegradable materials in their design and fabrication, is still in high demand. Herein we present an easy-to-use, cost-effective, selective, nontoxic, and disposable photoluminescent nanopaper-based assay kit with a smartphone readout for easy diagnosis of neonatal jaundice through visual determination of Bilirubin (BR) in infants' blood samples. The developed BR assay kit comprises highly photoluminescent carbon dot (CD) sensing probes embedded in a bacterial cellulose (BC) nanopaper substrate (CDBN). The photoluminescence (PL) of the developed BR sensor is quenched in the presence of BR as a PL quencher and then selectively recovered upon blue light (λ = 470 nm) exposure, due to conversion of the unconjugated BR to the colorless oxidation products (non-PL quencher) through BR photoisomerization and photooxidation, that subsequently leads to selective PL enhancement of CDBN. The recovered PL intensity of the developed BR assay kit, which was monitored by integrated smartphone camera, was linearly proportional to the concentration of BR in the range of 2-20 mg dL-1. The feasibility of real application of the fabricated smartphone-based BR assay kit was also confirmed via comparing the results of our method with a clinical reference method for determination of BR concentration in infant's blood samples. With the advantages of nontoxicity and the extraordinary physicochemical properties of photoluminescent BC nanopaper as the sensing substrate, along with those of smartphone technology, we believe that our developed smartphone-based BR assay kit, as an easy-to-use, cost-effective (∼0.01 Euro per test), portable and novel sensing bioplatform, can be potentially exploited for sensitive, specific, rapid, and easy BR detection and jaundice diagnosis at the point of care (POC) and in routine clinical laboratories as well.

Instrument-free argentometric determination of chloride via trapezoidal distance-based microfluidic paper devices

Chloride (Cl−) is an inorganic anion present in a broad range of samples (e.g. biological, environmental, food, water, etc.), the determination of which is of widespread significance. In this work, we translate the well-established traditional argentometric method (Mohr's precipitation titration) into a small, simple, portable, and low-cost paper-based microfluidic diagnostic device, which provides rapid and quantitative analysis. The developed device enables the determination of chloride sample volumes as small as 5 μL. A distance-based detection method is implemented providing fully instrument-free quantitation. The beneficial effects of channel geometry (variable widths with constant heights) on analytical parameters were investigated. Trapezoidal channels (channel width changes linearly with height) were used to create a gradient of paper surface (titrant) available for the reaction, compared to the typical uniform rectangular channels (constant channel width). The trapezoid with increasing width offered higher sensitivity and lower detection limits (i.e. 0.05 mM vs 0.1 mM from the rectangular channel) for chloride determination across the concentration range of 0.05–25 mM. In addition, the effect of concentration of the deposited reagent on the obtained distance signals was investigated using varying concentrations of titrant (AgNO3), which allowed determination of chloride across a wider dynamic range (up to 200 mM). The utility of the paper devices was demonstrated by determination of chloride in a variety of matrices including body fluids (sweat, serum, and urine) and water samples (drinking, mineral, river water).

Effect of calf muscle electrical stimulation on rostral fluid shift, snoring and obstructive sleep apnea

Study objectivesOvernight fluid shift from the legs into the neck may contribute to the pathogenesis of snoring and obstructive sleep apnea (OSA). The present study investigates the effects of calf muscle electrical stimulation (ES) on reducing leg fluid accumulation while seated, subsequent rostral fluid shift on lying down, and the impact on snoring and OSA. MethodsSixteen non-obese, normotensive men with OSA participated in the study. On the first study day, participants sat for 150 min receiving either active or sham ES through random allocation, then lied supine for 60 min. While seated and supine, leg and neck fluid volumes were measured using bioelectrical impedance to determine the magnitude of fluid shift. On the night of the study day, participants wore a portable sleep apnea diagnostic device overnight to measure snoring and sleep apnea severity. One week later, participants crossed over to the other study condition. ResultsActive calf muscle ES reduced leg fluid accumulation by 46% while seated. Upon lying supine, active ES reduced fluid shift out of the legs by 17% and reduced neck fluid accumulation by 31%. This led to a 15% reduction in snoring index, but did not alleviate OSA. ConclusionsOne session of calf muscle ES was effective at reducing leg fluid accumulation and rostral fluid shift, which led to a modest reduction in the snoring index, but not OSA. Despite this lack of effect of calf muscle ES in attenuating OSA severity, the reduction in the snoring index suggests that it did have an effect, albeit mild, on upper-airway mechanics.

A micro-dispenser for long-term storage and controlled release of liquids

The success of lab-on-a-chip systems may depend on a low-cost device that incorporates on-chip storage and fluidic operations. To date many different methods have been developed that cope separately with on-chip storage and fluidic operations e.g., hydrophobic and capillary valves pneumatic pumping and blister storage packages. The blister packages seem difficult to miniaturize and none of the existing liquid handling techniques despite their variety are capable of proportional repeatable dispensing. We report here on an inexpensive robust and scalable micro-dispenser that incorporates long-term storage and aliquoting of reagents on different microfluidics platforms. It provides long-term shelf-life for different liquids enables precise dispensing on lab-on-a-disc platforms and less accurate but proportional dispensing when operated by finger pressure. Based on this technology we introduce a method for automation of blood plasma separation and multi-step bioassay procedures. This micro-dispenser intends to facilitate affordable portable diagnostic devices and accelerate the commercialization of lab-on-a-chip devices.

Advances in nanoplasmonic biosensors for clinical applications.

Biomarkers are unquestionable biological indicators for diagnosis and therapeutic interventions providing appropriate classification of a wide range of health disorders and risk factors. Nonetheless, the detection and quantification of biomarkers need to be tested with sufficient reliability by robust analytical methods in order to assure clinical performance in health care settings. Since the analytical performance is determined by the sensitivity and specificity of the method employed, techniques have been intensively refined in order to avoid the misinterpretation of results and undesirable bias. Although biomarkers can be detected with the existing analytical techniques, to reproducibly quantify them in decentralized settings or remote locations with the required accuracy is still a challenge. Currently, only a few point-of-care devices for biomarker evaluation are commercially available. Thus, more focused research efforts are needed to overcome these limitations in order to provide universal patient-centered care platforms. To this end, plasmonic biosensors can be conveniently used as portable diagnostic devices for attaining timely and cost-effective clinical outcomes. The development of enhanced performance based on nanoplasmonics technology opens the way for sensor miniaturization, multiplexing and point of care testing. This review covers recent advances and applications of plasmonic and nanoplasmonic biosensors intended for biomarker diagnosis in clinical practice, including cancer, cardiovascular and neurodegenerative diseases. The review specially focuses on: (i) recent progress in plasmonics development including the design of singular nanostructured surfaces, (ii) novel chemical functionalization strategies for the appropriate incorporation of bioreceptors and (iii) plasmonic applications as real operative devices in the clinical field. Future prospects in the use of nanoplasmonic sensor platforms for personalised quantification and management of biomarkers directly in body fluids will also be discussed.

Paper-based immunosensor utilizing dielectrophoretic trapping of microprobes for quantitative and label free detection using electrochemical impedance spectroscopy.

In this study, we have developed a novel paper based immunoassay for the quantitative detection of immunoreactions using electrochemical impedance spectroscopy. Paper provides an attractive platform for fabrication of simple, low cost, and portable diagnostic devices as it allows passive liquid transport, is biocompatible, and has tunable properties such as hydrophilicity, flexibility, permeability, and reactivity. We have used screen-printing to fabricate interdigitated electrodes (finger width and gap of 200 μm) on the paper substrate, while UV-lithography enables patterning of the paper into hydrophobic/hydrophilic regions. As a proof of concept, we have used this immunosensor to detect the immune response of Human Serum Albumin (HSA) antibody-antigen complex formation. To enable efficient immobilization of HSA antibodies, we have utilized dielectrophoresis to trap microprobes (MPs) on the electrode surface. The microprobes consist of an alumina nanoparticle core with a well-adhered polyaniline outer coating to which the HSA antibodies are conjugated in an oriented manner via covalent chemistry. The efficacy of the impedance-based immunosensor is compared when MPs are immobilized specifically on the electrode surface using dielectrophoresis (DEP) as opposed to being dropped and immobilized via physical absorption on the entire sensing area. Results show that a more reproducible and sensitive response is observed when DEP is utilized to trap the microprobes. Furthermore, the normalized impedance variation during immunosensing shows a linear dependence on the concentration of HSA with an observed limit of detection of 50 μg/ml, which is lower than conventionally used paper based urine dipsticks used for urinary protein detection. Thus, we have developed a low cost paper based immunoassay platform that can be used for the quantitative point of care detection of a wide range of immunoreactions.

New advances in microfluidic flow cytometry.

In recent years, researchers are paying the increasing attention to the development of portable microfluidic diagnostic devices including microfluidic flow cytometry for the point-of-care testing. Microfluidic flow cytometry, where microfluidics and flow cytometry work together to realize novel functionalities on the microchip, provides a powerful tool for measuring the multiple characteristics of biological samples. The development of a portable, low-cost, and compact flow cytometer can benefit the health care in underserved areas such as Africa or Asia. In this article, we review recent advancements of microfluidics including sample pumping, focusing and sorting, novel detection approaches, and data analysis in the field of flow cytometry. The challenge of microfluidic flow cytometry is also examined briefly.

Obstructive sleep apnea negatively impacts objectively measured physical activity.

Obesity and obstructive sleep apnea (OSA) are frequent comorbid conditions. The impact of OSA on objectively measured physical activity (PA), independent of obesity, is not clear. The purpose of this study is to examine the effect of OSA on PA measured via accelerometer. Overweight-to-obese individuals were recruited and screened for the presence of OSA via portable diagnostic device and divided into an OSA (n = 35) and control group (n = 24). Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Body composition was assessed with dual-energy X-ray absorptiometry. Subjects wore an accelerometer (Actigraph GT3X+, Actigraph Corp., Pensacola, FL) for a minimum of 4 and maximum of 7days, including at least one weekend day. There were no group differences in body mass index (BMI) or daytime sleepiness. Waist and neck circumference were higher in the OSA group. The OSA group was significantly older than the control group. The OSA group had fewer steps, moderate intensity minutes, moderate-to-vigorous minutes, number of PA bouts per day (≥ moderate intensity PA for ≥ 10 consecutive minutes), and total number of PA bouts. When adjusted for age, the PA bout data was no longer significant. Individuals screened as likely possessing OSA were less physically active than individuals without OSA when measured through objective means. We found no group differences in daytime sleepiness, BMI, or percent fat, suggesting other mechanisms than obesity and sleepiness for this difference.

Combined detection of C-reactive protein and PBMC quantification from whole blood in an integrated lab-on-a-disc microfluidic platform

There is an increasing need for portable and low-cost diagnostic devices for detecting inflammatory/infectious diseases in a rapid and user-friendly fashion. Here, we present a lab-on-a-disc solution, which performs automated sample pre-treatment and combinedly detects small molecules and counts cells in a whole blood sample with a volume of 8.75 μL with a sample to answer time of 14 min. It is used to detect two common inflammation/infection biomarkers, C-reactive protein (CRP) and peripheral blood mononuclear cell (PBMC) count. The whole blood sample was separated into plasma and PBMC fractions using density gradient centrifugation and centrifugo-pneumatic valving. On-disc CRP detection was performed in the extracted plasma using a CRP-antibody-functionalized magnetic nanobead (MNB)-based agglutination assay and a Blu-ray-based optomagnetic detection unit. On-disc PBMC scanning and quantification was performed using an optical imaging unit. Both detection units were integrated on the centrifugal platform and the entire study was automated in order to ensure reliability of the assay and user-friendliness of the method. We measured the CRP level of subjects with different CRP levels and obtained approximately 73% PBMC extraction efficiency compared to hospital results. The concurrent/combined detection of these two common biomarkers in an automated microfluidic platform with integrated detection units and with a low sample-to-answer time is a significant step forward towards a low-cost, out-of-lab, and portable tool to detect multiple biomarkers of significantly different nature (molecules and cells).

Obstructive Sleep Apnea Negatively Impacts Objectively Measured Physical Activity

Obstructive sleep apnea (OSA) is a disorder that results daytime sleepiness and fatigue. Additionally, OSA increases the risk for cardiovascular disease and diabetes, which is exacerbated by sedentary behavior. Obesity and OSA are frequent co-morbid conditions, so the impact of OSA, independent of obesity, on physical activity (PA) is not clear. PURPOSE: To examine the effect of OSA on objectively measured PA via accelerometer. METHODS: Overweight-to-obese individuals were recruited and screened for the presence of OSA via portable diagnostic device and divided into an OSA group [n = 35; Age = 45.2 ± 12.0; body mass index (BMI) = 33.0 ± 5.7 kg/m2] and a Control group (n = 24; Age = 35.0 ± 11.7; BMI = 30.5 ± 4.3 kg/m2). Daytime sleepiness was assessed with the Epworth Sleepiness Scale questionnaire. Body composition was assessed with dual-energy X-ray absorptiometry. Subjects wore an accelerometer for a minimum of 4 and maximum of 7 days, including at least 1 weekend day. RESULTS: The OSA group’s mean OSA severity (Apnea-Hypopnea Index = 20.4 ± 17.6) classifies as “moderate OSA”. There were no group differences in BMI, percent fat, or daytime sleepiness. Waist (106.4 ± 11.7 vs. 98.6 ± 9.1) and neck circumference (41.9 ± 3.3 vs. 38.8 ± 2.7) were higher in the OSA group. The OSA group was significantly older than the control group. Pearson correlation analysis showed that age was not related to any PA variable except for the total number of moderate or greater PA bouts (PA for > 10 consecutive minutes) and the average number of bouts per day. The OSA group had fewer steps (6409.0 ± 2317.6 vs. 7856.8 ± 2942.7, P = 0.04), moderate intensity minutes (29.9 ± 15.1 vs. 44.2 ± 25.4, P < 0.01), moderate-to-vigorous minutes (33.0 ± 3.0 vs. 46.0 ± 5.4, P = 0.03), total number of bouts (3.2 ± 3.4 vs. 5.9 ± 5.0, P = 0.02), and number of bouts per day (0.5 ± 0.5 vs. 1.0 ± 0.8, P = 0.01). When adjusted for age, the PA bout data was no longer significant. CONCLUSION: Individuals screened as likely possessing OSA were less physically active than individuals without OSA when measured through objective means. We found no group differences in daytime sleepiness, BMI or percent fat, suggesting other mechanisms than obesity and sleepiness for this difference.

Ultrasensitive Enzyme-free Biosensor by Coupling Cyclodextrin Functionalized Au Nanoparticles and High-Performance Au-Paper Electrode.

Microfluidic paper-based analytical device (μPAD), originally developed for improving healthcare in developing countries, presents a simple yet powerful platform for performing low-cost and portable diagnostic devices. Here, we report an enzyme-free μPAD for the detection of two tumor markers. First, a porous structure of gold nanoparticle (AuNP)-modified paper working electrode (Au-PWE), with a feature of all-round conductivity and plenty of active sites favoring biological ligand attachment, was fabricated as a sensor substrate. Next, cyclodextrin functionalized AuNPs (CD@AuNPs) as dual mimicking enzyme were prepared to load secondary antibodies or peptide. On one sample zone, in the presence of carcinoembryonic antigen (CEA), CD@AuNPs could be introduced into the Au-PWE through a sandwich immunoreaction, boosting the electrochemical signal of o-phenylenediamine (o-PD) via the trigger of a cascade catalysis reaction toward glucose and o-PD, eventually resulting in the sensitive detection of CEA. On another working zone, with the introduction of another target prostate-specific antigen (PSA), peptide cleavage took place, which further led to CD@AuNPs being released from Au-PWE, and then, the variation of electrochemical signals was recorded for the detection of PSA. We demonstrated, using the device, that the detection of CEA and PSA clinically had high sensitivity, wide linear ranges, and low detection limits. We believe that our work provides a promising platform for point-of-care testing, especially in resource-limited regions.

Diagnosis of sleep apnea in patients with stable chronic heart failure using a portable sleep test diagnostic device.

ApneaLink is a portable device for the screening of sleep apnea, a prevalent and underdiagnosed comorbidity in heart failure patients. A prospective cross-sectional study in patients with chronic heart failure was carried out to assess the sensitivity and specificity of apnea-hypopnea index (AHI) measurements using ApneaLink against the standard polysomnography test. Adult patients with a prior hospitalization in an acute heart failure hospital unit were recruited for the study. All participants were tested for sleep apnea using ApneaLink and polysomnography simultaneously during an overnight stay at a sleep laboratory. Global sleep apnea was evaluated according to the AHI, which was analyzed and compared. Subpopulation comparison based on ejection fraction was not realized due to population size. Thirty-five patients with stable chronic heart failure completed the study (mean age 70.9 ± 10.5years and body mass index 30.0 ± 4.7kg/m2). Two patients were excluded due to insufficient study duration. ApneaLink had a sensitivity greater than 80% for all AHI measurements, and a specificity greater than 80% for all AHI measurements, except for AHI ≥ 5 events/h (61.5%). The results showed higher sensitivities and specificities at AHI values of ≥ 10 events/h (sensitivity 81.3% and specificity 84.2%) and ≥ 15 events/h (sensitivity 83.3% and specificity 91.3%). Correlation analysis showed that AHI measurements using ApneaLink and polysomnography had a strong and significant correlation (r = 0.794; P < 0.001). Our results suggest that ApneaLink could be used in clinical practice to identify heart failure patients with high (AHI ≥ 15 events/h) and low (AHI < 5 events/h) probability of having sleep apnea, sparing the need for a diagnostic polysomnography and thus potentially impacting prognosis by providing a more cost-effective and timely diagnosis of this non-cardiac comorbidity.

Recent Advances in Fluorescence Lifetime Analytical Microsystems: Contact Optics and CMOS Time-Resolved Electronics.

Fluorescence spectroscopy has become a prominent research tool with wide applications in medical diagnostics and bio-imaging. However, the realization of combined high-performance, portable, and low-cost spectroscopic sensors still remains a challenge, which has limited the technique to the laboratories. A fluorescence lifetime measurement seeks to obtain the characteristic lifetime from the fluorescence decay profile. Time-correlated single photon counting (TCSPC) and time-gated techniques are two key variations of time-resolved measurements. However, commercial time-resolved analysis systems typically contain complex optics and discrete electronic components, which lead to bulkiness and a high cost. These two limitations can be significantly mitigated using contact sensing and complementary metal-oxide-semiconductor (CMOS) implementation. Contact sensing simplifies the optics, whereas CMOS technology enables on-chip, arrayed detection and signal processing, significantly reducing size and power consumption. This paper examines recent advances in contact sensing and CMOS time-resolved circuits for the realization of fully integrated fluorescence lifetime measurement microsystems. The high level of performance from recently reported prototypes suggests that the CMOS-based contact sensing microsystems are emerging as sound technologies for application-specific, low-cost, and portable time-resolved diagnostic devices.

Impact of obstructive sleep apnea on cardiovascular outcomes in patients with acute symptomatic pulmonary embolism: Rationale and methodology for the POPE study.

In normotensive patients with acute symptomatic pulmonary embolism (PE), the effect of undiagnosed obstructive sleep apnea (OSA) on cardiovascular (CV) outcomes lacks clarity. The Prognostic Significance of Obstructive Sleep Apnea in Patients With Acute Symptomatic Pulmonary Embolism (POPE) study is a multicenter, observational study designed to prospectively assess the prognostic significance of concomitant OSA in hemodynamically stable outpatients with acute symptomatic PE. Adult patients with acute stable PE are eligible. Recruited patients undergo an overnight sleep study using a level III portable diagnostic device within 7 days (and preferably within 48 hours) of diagnosis of PE. The sleep tracings are analyzed by a certified sleep technologist and audited by a sleep physician, both of whom are blinded to other study data. The patients are divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study uses a composite of PE-related death, CV death, clinical deterioration requiring an escalation of treatment, or nonfatal CV events (recurrent venous thromboembolism, acute myocardial infarction, or stroke) within 30 days after the diagnosis of PE as the primary outcome. The projected sample size of 225 patients will provide 80% power to test the hypothesis that OSA will increase the primary outcome from 7% in the non-OSA group to 20% in the OSA group, with α ≤0.05. The trial results will be important to understand the burden and CV effects of OSA in PE patients.

Towards Multiplex Molecular Diagnosis-A Review of Microfluidic Genomics Technologies.

Highly sensitive and specific pathogen diagnosis is essential for correct and timely treatment of infectious diseases, especially virulent strains, in people. Point-of-care pathogen diagnosis can be a tremendous help in managing disease outbreaks as well as in routine healthcare settings. Infectious pathogens can be identified with high specificity using molecular methods. A plethora of microfluidic innovations in recent years have now made it increasingly feasible to develop portable, robust, accurate, and sensitive genomic diagnostic devices for deployment at the point of care. However, improving processing time, multiplexed detection, sensitivity and limit of detection, specificity, and ease of deployment in resource-limited settings are ongoing challenges. This review outlines recent techniques in microfluidic genomic diagnosis and devices with a focus on integrating them into a lab on a chip that will lead towards the development of multiplexed point-of-care devices of high sensitivity and specificity.