Smartphone based non-invasive salivary glucose biosensor.

The present work deals with the development of a non-invasive optical glucose biosensor using saliva samples and a smartphone. The sensor was fabricated with a simple methodology by immobilization of Glucose oxidase enzyme along with a pH responsive dye on a filter paper based strip. The strip changes color upon reaction with glucose present in saliva and the color changes were detected using a smartphone camera through RGB profiling. This standalone biosensor showed good sensitivity and low interference while operating within 20 s response time. We used various means for improvements such as the use of slope method instead of differential response; use of a responsive pH indicator and made numerous tweaks in the smartphone app. Calibration with spiked saliva samples with slopes for (R + G + B) pixels revealed an exponentially increasing calibration curve with a linear detection range of 50-540 mg/dL, sensitivity of 0.0012 pixels sec-1/mg dL-1 and LOD of 24.6 mg/dL. The biosensor was clinically validated on both healthy and diabetic subjects divided into several categories based on sex, age, diabetic status etc. and correlation between blood and salivary glucose has been established for better standardization of the sensor. Correlation of 0.44 was obtained between blood and salivary glucose in healthy individuals whereas it was 0.64 and 0.94 in case of prediabetic and diabetic patients respectively. The developed biosensor has the potential to be used for mass diagnosis of diabetes especially in such areas where people remain prohibited from routine analysis due to high healthcare cost. Apart from that, a smartphone would be the only device the user needs for this measurement, along with a disposable low cost test strip.

[1]  P. Abikshyeet,et al.  Glucose estimation in the salivary secretion of diabetes mellitus patients , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[2]  John R. White,et al.  Smartphone-Based Glucose Monitors and Applications in the Management of Diabetes: An Overview of 10 Salient “Apps” and a Novel Smartphone-Connected Blood Glucose Monitor , 2012, Clinical Diabetes.

[3]  G G Guilbault,et al.  Non-invasive biosensors in clinical analysis. , 1995, Biosensors & bioelectronics.

[4]  Elisa Michelini,et al.  A 3D-printed device for a smartphone-based chemiluminescence biosensor for lactate in oral fluid and sweat. , 2014, The Analyst.

[5]  Sandeep Kumar Vashist,et al.  Commercial Smartphone-Based Devices and Smart Applications for Personalized Healthcare Monitoring and Management , 2014, Diagnostics.

[6]  Jonathan C. Claussen,et al.  Nanostructuring Platinum Nanoparticles on Multilayered Graphene Petal Nanosheets for Electrochemical Biosensing , 2012 .

[7]  Hassan M E Azzazy,et al.  Power-free chip enzyme immunoassay for detection of prostate specific antigen (PSA) in serum. , 2013, Biosensors & bioelectronics.

[8]  Aldo Roda,et al.  Smartphone-based biosensors: A critical review and perspectives , 2016 .

[9]  V. Gupta,et al.  Noninvasive Method for Glucose Level Estimation by Saliva , 2013 .

[10]  Radhika Sashikumar,et al.  Salivary glucose levels and oral candidal carriage in type II diabetics. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[11]  P. Sönksen,et al.  Glucose Concentrations in Parotid Fluid and Venous Blood of Patients Attending a Diabetic Clinic1 , 1981, Journal of the Royal Society of Medicine.

[12]  Jessica Doyle,et al.  Noninvasive in vivo glucose sensing on human subjects using mid-infrared light. , 2014, Biomedical optics express.

[13]  M. Cohen,et al.  Salivary composition in diabetic patients. , 1988, The Journal of diabetic complications.

[14]  Hyun C. Yoon,et al.  Paper-based glucose biosensing system utilizing a smartphone as a signal reader , 2014, BioChip Journal.

[15]  Hak Soo Choi,et al.  Smartphone-Based Fluorescent Diagnostic System for Highly Pathogenic H5N1 Viruses , 2016, Theranostics.

[16]  Nuno M Reis,et al.  Portable smartphone quantitation of prostate specific antigen (PSA) in a fluoropolymer microfluidic device. , 2015, Biosensors & bioelectronics.

[17]  E. Benjamin,et al.  Self-Monitoring of Blood Glucose: The Basics , 2002 .

[18]  Li Jiang,et al.  Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics. , 2014, Lab on a chip.

[19]  Jung-Hyun Lee,et al.  Real-time measurement of human salivary cortisol for the assessment of psychological stress using a smartphone , 2014 .

[20]  M J CAMPBELL,et al.  GLUCOSE IN THE SALIVA OF THE NON-DIABETIC AND THE DIABETIC PATIENT. , 1965, Archives of oral biology.

[21]  Qingjun Liu,et al.  Biosensors and bioelectronics on smartphone for portable biochemical detection. , 2016, Biosensors & bioelectronics.

[22]  Sandeep Kumar Jha,et al.  A paper strip based non-invasive glucose biosensor for salivary analysis. , 2015, Biosensors & bioelectronics.

[23]  W. dodds,et al.  Acid neutralizing capacity of human saliva. , 1982, Gastroenterology.

[24]  S. Dreizen,et al.  The buffer capacity of saliva as a measure of dental caries activity. , 1946, The Journal of the Alabama Academy of Science.

[25]  S. Amer,et al.  Salivary glucose concentrations in patients with diabetes mellitus--a minimally invasive technique for monitoring blood glucose levels. , 2001, Pakistan journal of pharmaceutical sciences.

[26]  J. Shaw,et al.  IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. , 2011, Diabetes research and clinical practice.

[27]  I. Cook,et al.  An improved dinitrosalicylic acid method for determining blood and cerebrospinal fluid sugar levels , 1962, Journal of Clinical Pathology.

[28]  Aldo Roda,et al.  A simple and compact smartphone accessory for quantitative chemiluminescence-based lateral flow immunoassay for salivary cortisol detection. , 2015, Biosensors & bioelectronics.

[29]  Aldo Roda,et al.  Smartphone-based enzymatic biosensor for oral fluid L-lactate detection in one minute using confined multilayer paper reflectometry. , 2017, Biosensors & bioelectronics.

[30]  B. M. Jaffar Ali,et al.  Smartphone based bacterial detection using biofunctionalized fluorescent nanoparticles , 2014, Microchimica Acta.

[31]  P. Timsina,et al.  Mobile Applications for Diabetes Self-Management: Status and Potential , 2013, Journal of diabetes science and technology.

[32]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[33]  A. Panchbhai,et al.  Correlation of Salivary Glucose Level with Blood Glucose Level in Diabetes Mellitus , 2012, Journal of oral & maxillofacial research.