Medically Relevant Assays with a Simple Smartphone and Tablet Based Fluorescence Detection System

Cell phones and smart phones can be reconfigured as biomedical sensor devices but this requires specialized add-ons. In this paper we present a simple cell phone-based portable bioassay platform, which can be used with fluorescent assays in solution. The system consists of a tablet, a polarizer, a smart phone (camera) and a box that provides dark readout conditions. The assay in a well plate is placed on the tablet screen acting as an excitation source. A polarizer on top of the well plate separates excitation light from assay fluorescence emission enabling assay readout with a smartphone camera. The assay result is obtained by analysing the intensity of image pixels in an appropriate colour channel. With this device we carried out two assays, for collagenase and trypsin using fluorescein as the detected fluorophore. The results of collagenase assay with the lowest measured concentration of 3.75 µg/mL and 0.938 µg in total in the sample were comparable to those obtained by a microplate reader. The lowest measured amount of trypsin was 930 pg, which is comparable to the low detection limit of 400 pg for this assay obtained in a microplate reader. The device is sensitive enough to be used in point-of-care medical diagnostics of clinically relevant conditions, including arthritis, cystic fibrosis and acute pancreatitis.

[1]  A. Strusberg,et al.  [Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes incubated]. , 2000, Revista de la Facultad de Ciencias Medicas.

[2]  Y. Urano,et al.  Orthogonality of Calcium Concentration and Ability of 4,5-Diaminofluorescein to Detect NO* , 2002, The Journal of Biological Chemistry.

[3]  T. Sawai,et al.  Determination of interstitial collagenase (MMP-1) in patients with rheumatoid arthritis. , 1995, Annals of the rheumatic diseases.

[4]  J. Artigas,et al.  Serum trypsin levels in acute pancreatic and non-pancreatic abdominal conditions. , 1981, Postgraduate medical journal.

[5]  Derek Tseng,et al.  Fluorescent imaging of single nanoparticles and viruses on a smart phone. , 2013, ACS nano.

[6]  G. Schmid-Schönbein,et al.  Protease Activity Increases in Plasma, Peritoneal Fluid, and Vital Organs after Hemorrhagic Shock in Rats , 2012, PloS one.

[7]  J. Joseph,et al.  Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. , 1999, Free radical biology & medicine.

[8]  JeanetteR. Crossle,et al.  DRIED-BLOOD SPOT SCREENING FOR CYSTIC FIBROSIS IN THE NEWBORN , 1979, The Lancet.

[9]  N. Bhardwaj,et al.  Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury. , 1992, Arthritis and rheumatism.

[10]  A. Rai,et al.  A smartphone dongle for diagnosis of infectious diseases at the point of care , 2015, Science Translational Medicine.

[11]  Hojeong Yu,et al.  Smartphone fluorescence spectroscopy. , 2014, Analytical chemistry.

[12]  S. Kennedy,et al.  A fluorescence-based protein assay for use with a microplate reader. , 1993, Analytical biochemistry.

[13]  Steve Feng,et al.  Rapid imaging, detection and quantification of Giardia lamblia cysts using mobile-phone based fluorescent microscopy and machine learning. , 2015, Lab on a chip.

[14]  T. D. Du Clos,et al.  Binding and Internalization of C-Reactive Protein by Fcgamma Receptors on Human Aortic Endothelial Cells Mediates Biological Effects , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[15]  D. Watson,et al.  Cystic fibrosis--its biochemical detection. , 1983, Clinical chemistry.

[16]  Aydogan Ozcan,et al.  Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array. , 2013, Lab on a chip.

[17]  Warren C W Chan,et al.  Automation Highlights from the Literature , 2015, Journal of laboratory automation.

[18]  U. Pick,et al.  Indications for an oligomeric structure and for conformational changes in sarcoplasmic reticulum Ca2+-ATPase labelled selectively with fluorescein. , 1980, Biochimica et biophysica acta.

[19]  B. Hazleman,et al.  The measurement of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis. , 1993, Arthritis and rheumatism.

[20]  H. Maeda,et al.  Fluorescence polarization assay of plasmin, plasminogen, and plasminogen activator. , 1980, Analytical biochemistry.

[21]  Pappenhagen Ar,et al.  Use of fluorescein-labeled fibrin for the determination of fibrinolytic activity. , 1962 .

[22]  J. Olwin,et al.  Use of fluorescein-labeled fibrin for the determination of fibrinolytic activity. , 1962, The Journal of laboratory and clinical medicine.

[23]  N. Slater,et al.  A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film. , 2011, Lab on a chip.

[24]  Thomas van Oordt,et al.  A smartphone-based colorimetric reader for bioanalytical applications using the screen-based bottom illumination provided by gadgets. , 2015, Biosensors & bioelectronics.

[25]  Hongying Zhu,et al.  Optical imaging techniques for point-of-care diagnostics. , 2013, Lab on a chip.

[26]  T. Schröder,et al.  Serum phospholipase A2, immunoreactive trypsin, and trypsin inhibitors during human acute pancreatitis. , 1982, Scandinavian journal of gastroenterology.

[27]  M. Walsh,et al.  Screening for cystic fibrosis by died blood spot trypsin assay. , 1982, Archives of disease in childhood.

[28]  R. D. Spencer,et al.  Design, construction, and two applications for an automated flow-cell polarization fluorometer with digital read out: enzyme-inhibitor (antitrypsin) assay and antigen-antibody (insulin-insulin antiserum) assay. , 1973, Clinical chemistry.

[29]  Hongying Zhu,et al.  Optofluidic fluorescent imaging cytometry on a cell phone. , 2011, Analytical chemistry.

[30]  Aydogan Ozcan,et al.  Integrated rapid-diagnostic-test reader platform on a cellphone. , 2012, Lab on a chip.

[31]  R. Lequin Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). , 2005, Clinical chemistry.

[32]  Xiyuan Liu,et al.  Smartphones for Cell and Biomolecular Detection , 2014, Annals of Biomedical Engineering.

[33]  Jae S. Lim,et al.  Two-Dimensional Signal and Image Processing , 1989 .

[34]  Hongying Zhu,et al.  Cost-effective and compact wide-field fluorescent imaging on a cell-phone. , 2011, Lab on a chip.