Balaji Srinivasan | Cornell University (original) (raw)

Papers by Balaji Srinivasan

Environmental Research, 2022

Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and g... more Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and growth, in addition to being a known carcinogen. The ability to accurately assess concentration of aflatoxin in the blood of at-risk individuals is therefore very important to inform public health policies and on-the-ground programs around the world. Venous blood is frequently used to quantify biomarkers of exposure such as AFB1-lysine adducts. However, venous blood collection methods are invasive, requiring highly trained staff, which makes this method challenging to implement, especially in resource-limited settings. In contrast, capillary blood collection by fingerprick is less invasive and has the potential for application in point-of-need monitoring. The aim of this exploratory study was to investigate the correlation and interchangeability of capillary and venous human blood samples in the quantification of AFB1-lysine adduct concentration. A total of 72 venous and capillary blood samples were collected from 36 women of reproductive age (16-49 years) in northern Uganda. All sample specimens were analyzed using high-performance liquid chromatography with fluorescence detection. Regression analysis and Bland-Altman analysis were performed to compare AFB1-lysine concentrations between venous and capillary sample pairs. Bland-Altman analysis of albumin-normalized AFB1-lysine data-bias was − 0.023 pg/mg-albumin and the 95% limits of agreement were 0.51 to − 0.56 pg/mg-albumin for log-transformed data. There was a positive correlation between albumin-normalized venous and capillary AFB1-lysine concentrations with r of 0.71 (p < .0001). A lack of any accepted clinical cutoff for aflatoxin exposure makes definition of an 'acceptable' limit for statistical analysis and comparison of methods challenging. Our data suggests a positive correlation between albumin-normalized AFB1-lysine concentrations in venous and capillary sample pairs, but relatively weak agreement and interchangeability based on Bland-Altman analysis.

ACS Publications, 2022

Vitamin A (VA) deficiency continues to be a major global health issue, despite measures to increa... more Vitamin A (VA) deficiency continues to be a major global health issue, despite measures to increase VA intake via consumption of staple foods such as edible oil. Portable quantitative and semiquantitative devices or test kits for internal quality control have the potential to overcome some of the limitations of traditional methods of testing, such as centralized laboratory, expensive equipment, and specially trained staff. This landscape analysis and comprehensive systematic mini-review catalogs and summarizes evidence on the analytical performance of portable quantitative and semiquantitative devices and test kits for the analysis of VA in edible oil. Studies or reports detailing the usability and validation of portable devices and/or test kits, as well as studies comparing device/test kit performance to a reference standard such as high-performance liquid chromatography (HPLC), were included. Identified devices and test kits were compared for performance versus the reference standard, usability, availability, and other characteristics. We identified four portable methods: two devices, the iCheck CHROMA and iCheck Chroma 3 from BioAnalyt; and two test kits, the QuickView from Bagco Enterprises and the Strategic Alliance for the Fortification of Vegetable Oils (SAFO) Test Kit by Badische Anilin and Soda Fabrik (BASF). Included studies reported the following: an internal validation of the portable method, a comparison of the portable method against a reference standard, a comparison of the portable method against another portable method, and several videos and company websites, which detailed device characteristics. iCheck CHROMA and QuickView quantified VA concentrations with high accuracy and precision compared to the reference standard for field-based quantification, were userfriendly, and provided results within 5 min. iCheck Chroma 3 requires more robust validation against a reference standard. We did not find data on internal validation or comparison against a reference standard for the current version of the SAFO test. Compared to QuickView and SAFO, the iCheck devices can transfer results to a hard drive or the Web, have an online order form for purchase, and meet a minimal set of criteria for point-of-need devices. iCheck, QuickView, and SAFO can quantify VA concentrations in the edible oils tested and determine whether a fortified oil meets country standards. Additional research is needed to validate these devices and test kits across additional oil types and document the ability to meet the minimal criteria for point-of-need devices suggested in this mini-review. Validation against a reference standard is required for SAFO. The limited number of portable methods available may be due to market saturation. Future market and use case analyses to inform the market size and utility of the different tests with publicly available data will allow new manufacturers, particularly those in lower-to-middle-income countries, to enter the market.

Current Research in Biotechnology, 2023

Aflatoxins (AFs) are naturally occurring mycotoxins known to cause a considerable threat to food ... more Aflatoxins (AFs) are naturally occurring mycotoxins known to cause a considerable threat to food safety and affect animal and health. Rapid and reliable analytical methods are crucial for preventing AF contamination in the global food supply chain. Many conventional AF detection methods involve complex sample preparation steps, lengthy analysis times, and multiple handling stages which lead to delays in obtaining results, in addition to being unaffordable in many settings with resource constraints. Herein, we demonstrate the proof of concept of a competitive immunochromatographic (IC) strip test for quantification of total AF using commercially available antibodies and a low-cost portable Cube TM analyzer. We conducted preliminary testing of our point-of-need (PON) AF detection method with corn samples and results indicated a good agreement when compared with gold standard HPLC method. Furthermore, a detection range of 5-50 ppb with detection time of 5 min, makes this technology suitable for rapid testing and meets the regulatory requirements for AF detection in food samples. We also demonstrate the real-time data sharing capabilities of the reader to a proof-of-concept centralized and cloud-based AF databank, that we developed to provide timely monitoring for different parts of food systems. It is critical for the test data to be easily accessible within a food systems dashboard to enable early warning, datadriven decision-making, rapid interventions, and improve overall coordination between various stakeholders within the food system.

SSRN Electronic Journal, 2021

Lab on a Chip, 2018

HYPER platform: affordable whole blood separation with unique cross-flow filtration that makes ra... more HYPER platform: affordable whole blood separation with unique cross-flow filtration that makes rapid diagnostics at point-of-care available.

Transactions of the ASABE, 2006

A chemiluminescence biosensing method combined with a microfluidic filter biochip was investigate... more A chemiluminescence biosensing method combined with a microfluidic filter biochip was investigated and evaluated for rapid and sensitive detection of Escherichia coli O157:H7, A microfluidic

Scientific Reports, 2016

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under ... more We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening.

Journal of laboratory automation, Jan 15, 2015

The significance of microfluidics-based and microelectromechanical systems-based biosensors has b... more The significance of microfluidics-based and microelectromechanical systems-based biosensors has been widely acknowledged, and many reviews have explored their potential applications in clinical diagnostics, personalized medicine, global health, drug discovery, food safety, and forensics. Because health care costs are increasing, there is an increasing need to remotely monitor the health condition of patients by point-of-care-testing. The demand for biosensors for detection of biological warfare agents has increased, and research is focused on ways of producing small portable devices that would allow fast, accurate, and on-site detection. In the past decade, the demand for rapid and accurate on-site detection of plant disease diagnosis has increased due to emerging pathogens with resistance to pesticides, increased human mobility, and regulations limiting the application of toxic chemicals to prevent spread of diseases. The portability of biosensors for on-site diagnosis is limited d...

Journal of laboratory automation, Jan 13, 2015

Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative t... more Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. TEER values are strong indicators of the integrity of the cellular barriers before they are evaluated for transport of drugs or chemicals. TEER measurements can be performed in real time without cell damage and generally are based on measuring ohmic resistance or measuring impedance across a wide spectrum of frequencies. The measurements for various cell types have been reported with commercially available measurement systems and also with custom-built microfluidic implementations. Some of the barrier models that have been widely characterized using TEER include the blood-brain barrier (BBB), gastrointestinal (GI) tract, and pulmonary models. Variations in these values can arise due to factors such as temperature, medium formulation, and passage number of cells. T...

2010 IEEE 5th International Conference on Nano/Micro Engineered and Molecular Systems, 2010

An experimental study was carried out to evaluate the performance of a polydimethylsiloxane (PDMS... more An experimental study was carried out to evaluate the performance of a polydimethylsiloxane (PDMS) based micromixer for heterogeneous immunoassays of insulin. The detection method is based on coupling the highly specific double-antibody sandwich immunoassay with the sensitive chemiluminescence of the Luminol-Hydrogen Peroxide reaction. Both the immune and chemiluminescence reactions are conducted in the micromixer, and the resultant light emission is detected by a highly sensitive photometer. The behavior of the luminol based chemiluminescence is parabolic with respect to time, and the maximum light intensity is used here to represent the output of the reaction. The current results indicate that at an actuation pressure of 15psi, an actuation frequency of 30Hz leads to the best reaction result. At these operating conditions, the detection limit of insulin is about 10-14 mol/L while the total reaction time of the insulin immunoassay in the micromixer is less than 5 minutes.

Journal of Visualized Experiments, 2014

2010 IEEE International Conference on Nano/Molecular Medicine and Engineering, 2010

An integrated polydimethysiloxane (PDMS) microfluidic system which is composed of two pneumatic m... more An integrated polydimethysiloxane (PDMS) microfluidic system which is composed of two pneumatic micropumps and one micromixer is developed for high-accuracy detection of insulin. The detection method is based on coupling the highly specific technique of 'double-antibody sandwich immunoassay' with the sensitive chemiluminescence of Luminol-Hydrogen Peroxide (H 2 O 2). The immune reactions and other related processes are carried out in the microfluidic system semi automatically. Sample transportation in the microfluidic system is accomplished by two pneumatic PDMS micropumps. Chemiluminescent measurement is conducted in a separate PDMS micromixer using a double-channel syringe pump to inject reagents. Light emitting from this mixer is detected by a highly sensitive photometer when the chemiluminescent regents flow through the mixer chamber. The results indicate that at an actuation pressure of 10psi, a mixer actuation frequency of 5Hz, and an injecting flow rate of 0.5 ml/min, the detection limit of the microfluidic system for insulin is about 10-10 M.

Journal of Virological Methods, 2011

Current methods for detection of avian influenza virus (AIV) based on virus culture and RT-PCR ar... more Current methods for detection of avian influenza virus (AIV) based on virus culture and RT-PCR are well established, but they are either time consuming or require specialized laboratory facilities and highly trained technicians. A simple, rapid, robust, and reliable test, suitable for use in the field or at the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s bedside, is urgently needed. In this study, the performance of a newly developed portable impedance biosensor was evaluated by comparison with real-time reverse transcriptase PCR (rRT-PCR) and virus culture for detection of AIV in tracheal and cloacal swab samples collected from experimentally H5N2 AIV infected chickens. The impedance biosensor system was based on a combination of magnetic nanobeads, which were coated with AIV subtype-specific antibody for capture (separation and concentration) of a target virus, and a microfluidic chip with an interdigitated array microelectrode for transfer and detection of target virus, and impedance measurement of the bio-nanobeads and AI virus complexes in a buffer solution. A comparison of results obtained from 59 swab samples using virus culture, impedance biosensor and rRT-PCR methods showed that the impedance biosensor technique was comparable in sensitivity and specificity to rRT-PCR. Detection time for the impedance biosensor is less than 1h.

Biosensors and Bioelectronics, 2012

Avian influenza virus (AIV) subtype H5N1 was first discovered in the 1990 s and since then its em... more Avian influenza virus (AIV) subtype H5N1 was first discovered in the 1990 s and since then its emergence has become a likely source of a global pandemic and economic loss. Currently accepted gold standard methods of influenza detection, viral culture and rRT-PCR, are time consuming, expensive and require special training and laboratory facilities. A rapid, sensitive, and specific screening method is needed for in-field or bedside testing of AI virus to effectively implement quarantines and medications. Therefore, the objective of this study was to improve the specificity and sensitivity of an impedance biosensor that has been developed for the screening of AIV H5. Three major components of the developed biosensor are immunomagnetic nanoparticles for the separation of AI virus, a microfluidic chip for sample control and an interdigitated microelectrode for impedance measurement. In this study polyclonal antibody against N1 subtype was immobilized on the surface of the microelectrode to specifically bind AIV H5N1 to generate more specific impedance signal and chicken red blood cells (RBC) were used as biolabels to attach to AIV H5N1 captured on the microelectrode to amplify impedance signal. RBC amplification was shown to increase the impedance signal change by more than 100% compared to the protocol without RBC biolabels, and was necessary for forming a linear calibration curve for the biosensor. The use of a second antibody against N1 offered much greater specificity and reliability than the previous biosensor protocol. The biosensor was able to detect AIV H5N1 at concentrations down to 10(3) EID(50)ml(-1) in less than 2h.

EBioMedicine, 2019

Background: Iron deficiency (ID) and anaemia are major health concerns, particularly in young chi... more Background: Iron deficiency (ID) and anaemia are major health concerns, particularly in young children. Screening for ID based on haemoglobin (Hb) concentration alone has been shown to lack sensitivity and specificity. The American Academy of Pediatrics (AAP) recommends soluble transferrin receptor (sTfR) as a promising approach to screen for iron deficiency. However, in most settings, assessment of iron status requires access to centralized laboratories. There is an urgent need for rapid, sensitive, and affordable diagnostics for sTfR at the point-of-care. Methods: An immunochromatographic assay-based point-of-care screening device was developed for rapid quantification of sTfR from a drop of serum within a few minutes. Performance optimization of the assay was done in sTfR-spiked buffer and commercially available sTfR calibrator, followed by a small-scale proof-of-concept validation with archived serum samples. Findings: On preliminary testing with archived serum samples and comparison with Ramco ELISA, a correlation of 0.93 (P b 0.0001) was observed, demonstrating its potential for point-of-care assessment of iron status. Interpretation: The analytical performance of the point-of-care sTfR screening device indicates the potential for application in home-use test kits and field settings, especially in low-and middle-income settings. An added advantage of sTfR quantification in combination with our previously reported serum ferritin diagnostics is in integration of Cook's equation as a quantitative and minimally-invasive indicator of total body iron stores.

Biosensors and Bioelectronics, 2018

Iron deficiency (ID) is an urgent public health problem that has devastating effects on maternal ... more Iron deficiency (ID) is an urgent public health problem that has devastating effects on maternal and child health. However, due to poor access and affordability, screening and diagnosis for ID is often limited to proxy hemoglobin measurements alone. Here, we report the development and validation of ironPhone, a mobiledevice coupled portable diagnostics for quantification of serum ferritin concentrations, an iron status biomarker, within a few minutes, from a drop of fingerprick blood. The ironPhone diagnostic platform comprises of a smartphone accessory, an app, and a disposable lateral flow immunoassay test strip to quantify serum ferritin. For initial validation in the lab, we optimized and evaluated the performance of ironPhone with known ferritin concentrations in spiked buffer and serum samples. Following lab validation, we performed a human validation by collecting fingerprick whole blood samples from 20 participants to assess iron status using ironPhone and compared the results with the laboratory standard IMMULITE 2000 analyzer. Findings from the ironPhone for the buffer and spiked serum samples provided a calibration curve with R 2 values of 0.97 (n=27) and 0.93 (n=12), respectively. On comparison with the laboratory standard IMMULITE analyzer in whole blood samples, a correlation of 0.92 (P < 0.0001) was observed with a sensitivity of over 90% for predicting ID (ferritin < 15.0 µg/L) via the ironPhone, demonstrating its promise for iron status assessment at the point-ofcare.

Current Opinion in Biotechnology, 2017

Precision nutrition encompasses prevention and treatment strategies for optimizing nutritional st... more Precision nutrition encompasses prevention and treatment strategies for optimizing nutritional status that consider individual variability in diet, lifestyle, environment and genes by accurately determining an individual's nutritional status. This is particularly important as malnutrition now affects a third of the global population, with most of those affected or their care providers having limited means of determining their nutritional status. Similarly, program implementers often have no way of determining the impact or success of their interventions, thus hindering their scale-up. Exciting new developments in the area of point-of-care diagnostics promise to provide improved access to nutritional status assessment, as a first step towards enabling precision nutrition and tailored interventions at both the individual and community levels. In this review, we focus on the current advances in developing portable diagnostics for assessment of nutritional status at point-of-care, along with the numerous design challenges in this process and potential solutions.

Lab Chip, 2016

Advancements in LOC technologies are enabling personalized nutrition diagnostics at the point-of-... more Advancements in LOC technologies are enabling personalized nutrition diagnostics at the point-of-need.

Proceedings of the National Academy of Sciences of the United States of America, Jan 19, 2017

Micronutrient deficiencies such as those of vitamin A and iron affect a third of the world's ... more Micronutrient deficiencies such as those of vitamin A and iron affect a third of the world's population with consequences such as night blindness, higher child mortality, anemia, poor pregnancy outcomes, and reduced work capacity. Many efforts to prevent or treat these deficiencies are hampered by the lack of adequate, accessible, and affordable diagnostic methods that can enable better targeting of interventions. In this work, we demonstrate a rapid diagnostic test and mobile enabled platform for simultaneously quantifying iron (ferritin), vitamin A (retinol-binding protein), and inflammation (C-reactive protein) status. Our approach, enabled by combining multiple florescent markers and immunoassay approaches on a single test, allows us to provide accurate quantification in 15 min even though the physiological range of the markers of interest varies over five orders of magnitude. We report sensitivities of 88%, 100%, and 80% and specificities of 97%, 100%, and 97% for iron defi...

This paper reports a multilayered, automated PDMS based microTAS for rapid, high-sensitivity and ... more This paper reports a multilayered, automated PDMS based microTAS for rapid, high-sensitivity and point-of-care insulin detection. Two generations of microTAS differing in their design complexity and insulin detection protocol were compared. The first generation microTAS includes one micropump, one micromixer and interdigitated electrodes to perform flow through impedance spectroscopy for insulin detection with a detection limit of 10-5 M achieved within 20 min. The second generation microTAS includes multiple micropumps and valves, and is based on double antibody sandwich chemiluminescence immunoassay for insulin detection with a detection limit of 2.6 t 10-10 M achieved within 10 min.