Abstract
Recent advances in biomedical science and technology have played a significant role in the development of new sensors and assays for cell and biomolecular detection. Generally, these efforts are aimed at reducing the complexity and costs associated with diagnostic testing so that it can be performed outside of a laboratory or hospital setting, requiring minimal equipment and user involvement. In particular, point-of-care (POC) testing offers immense potential for many important applications including medical diagnosis, environmental monitoring, food safety, and biosecurity. When coupled with smartphones, POC systems can offer portability, ease of use and enhanced functionality while maintaining performance. This review article focuses on recent advancements and developments in smartphone-based POC systems within the last 6 years with an emphasis on cell and biomolecular detection. These devices typically comprise multiple components, such as detectors, sample processors, disposable chips, batteries, and software, which are integrated with a commercial smartphone. One of the most important aspects of developing these systems is the integration of these components onto a compact and lightweight platform that requires minimal power. Researchers have demonstrated several promising approaches employing various detection schemes and device configurations, and it is expected that further developments in biosensors, battery technology and miniaturized electronics will enable smartphone-based POC technologies to become more mainstream tools in the scientific and biomedical communities.
Similar content being viewed by others
References
Anderson, G. F., P. S. Hussey, B. K. Frogner, and H. R. Waters. Health spending in the United States and the rest of the industrialized world. Health Aff. (Millwood) 24:903–914, 2005.
Anker, S. D., F. Koehler, and W. T. Abraham. Telemedicine and remote management of patients with heart failure. The Lancet 378:731–739, 2011.
Auerbach, D. I., and A. L. Kellermann. A decade of health care cost growth has wiped out real income gains for an average US family. Health Aff. (Millwood) 30:1630–1636, 2011.
Bishara, W., U. Sikora, O. Mudanyali, T.-W. Su, O. Yaglidere, S. Luckhart, and A. Ozcan. Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array. Lab. Chip 11:1276, 2011.
Braun, R. P., J. L. Vecchietti, L. Thomas, C. Prins, L. E. French, A. J. Gewirtzman, J.-H. Saurat, and D. Salomon. Telemedical wound care using a new generation of mobile telephones: a feasibility study. Arch. Dermatol. 141:254–258, 2005.
Breslauer, D. N., R. N. Maamari, N. A. Switz, W. A. Lam, and D. A. Fletcher. Mobile Phone Based Clinical Microscopy for Global Health Applications. PLoS ONE 4:e6320, 2009.
Cheng, X., A. Gupta, C. Chen, R. G. Tompkins, W. Rodriguez, and M. Toner. Enhancing the performance of a point-of-care CD4 + T-cell counting microchip through monocyte depletion for HIV/AIDS diagnostics. Lab. Chip 9:1357–1364, 2009.
Cheng, X., D. Irimia, M. Dixon, K. Sekine, U. Demirci, L. Zamir, R. G. Tompkins, W. Rodriguez, and M. Toner. A microfluidic device for practical label-free CD4 + T cell counting of HIV-infected subjects. Lab. Chip 7:170, 2007.
Chin, C. D., V. Linder, and S. K. Sia. Commercialization of microfluidic point-of-care diagnostic devices. Lab. Chip 12:2118, 2012.
Coskun, A. F., R. Nagi, K. Sadeghi, S. Phillips, and A. Ozcan. Albumin testing in urine using a smart-phone. Lab. Chip 13:4231–4238, 2013.
Fang, X., Y. Liu, J. Kong, and X. Jiang. Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens. Anal. Chem. 82:3002–3006, 2010.
Filipovic, N., R. Stojanovic, M. Debevc, and G. Devedzic. On line ECG processing and visualization using android SmartPhone, 2013.doi:10.1109/MECO.2013.6601326.
Fronczek, C. F., T. S. Park, D. K. Harshman, A. M. Nicolini, and J.-Y. Yoon. Paper microfluidic extraction and direct smartphone-based identification of pathogenic nucleic acids from field and clinical samples. RSC Adv. 4:11103, 2014.
Gallegos, D., K. D. Long, H. Yu, P. P. Clark, Y. Lin, S. George, P. Nath, and B. T. Cunningham. Label-free biodetection using a smartphone. Lab. Chip 13:2124–2132, 2013.
Gerche, A. L., A. T. Burns, D. J. Mooney, W. J. Inder, A. J. Taylor, J. Bogaert, A. I. MacIsaac, H. Heidbüchel, and D. L. Prior. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur. Heart J. 33:998–1006, 2012.
Gervais, L., N. de Rooij, and E. Delamarche. Microfluidic chips for point-of-care immunodiagnostics. Adv. Mater. 23:H151–H176, 2011.
Giavazzi, F., M. Salina, E. Ceccarello, A. Ilacqua, F. Damin, L. Sola, M. Chiari, B. Chini, R. Cerbino, T. Bellini, and M. Buscaglia. A fast and simple label-free immunoassay based on a smartphone. Biosens. Bioelectron. 58:395–402, 2014.
Giordano, B. C., J. Ferrance, S. Swedberg, A. F. R. Hühmer, and J. P. Landers. Polymerase chain reaction in polymeric microchips: DNA amplification in less than 240 seconds. Anal. Biochem. 291:124–132, 2001.
Global Mobile Statistics 2013, Part A: mobile subscribers; handset market share; mobile operators. http://mobithinking.com/mobile-marketing-tools/latest-mobile-stats/a.
Görlinger, K., D. Fries, D. Dirkmann, C. F. Weber, A. A. Hanke, and H. Schöchl. Reduction of Fresh Frozen Plasma Requirements by Perioperative Point-of-Care Coagulation Management with Early Calculated Goal-Directed Therapy. Transfus. Med. Hemotherapy 39:104–113, 2012.
Goroso, D. G., R. R. da Silva, L. R. Battistella, M. Odstrcil, and M. Paolini. Monitoring heart rate variability online using e-health oriented 3G mobile telephone services. J. Phys. Conf. Ser. 477:012036, 2013.
Han, J.-H., B. C. Heinze, and J.-Y. Yoon. Single cell level detection of Escherichia coli in microfluidic device. Biosens. Bioelectron. 23:1303–1306, 2008.
Haun, J. B., C. M. Castro, R. Wang, V. M. Peterson, B. S. Marinelli, H. Lee, and R. Weissleder. Micro-NMR for rapid molecular analysis of human tumor samples. Sci. Transl. Med. 3:71ra16, 2011.
Jamal, S., and Y. K. Agrawal. Advances in microfluidics: lab-on-a-chip to point of care diagnostic devices. Adv. Sci. Eng. Med. 5:385–394, 2013.
Jiang, J., X. Wang, R. Chao, Y. Ren, C. Hu, Z. Xu, and G. L. Liu. Smartphone based portable bacteria pre-concentrating microfluidic sensor and impedance sensing system. Sens. Actuators B Chem. 193:653–659, 2014.
Jin, Z., Y. Sun, and A. C. Cheng. Predicting cardiovascular disease from real-time electrocardiographic monitoring: An adaptive machine learning approach on a cell phone. 2009. doi:10.1109/IEMBS.2009.5333610.
Kadlec, M. W., D. You, J. C. Liao, and P. K. Wong. A cell phone-based microphotometric system for rapid antimicrobial susceptibility testing. J. Lab. Autom. 19(3):258–266, 2013. doi:10.1177/2211068213491095.
Khandoker, A. H., J. Black, and M. Palaniswami. Smartphone-based low cost oximeter photoplethysmography, 2010. doi:10.1109/ICELCE.2010.5700773.
Khandurina, J., T. E. McKnight, S. C. Jacobson, L. C. Waters, R. S. Foote, and J. M. Ramsey. Integrated system for rapid PCR-based DNA analysis in microfluidic devices. Anal. Chem. 72:2995–3000, 2000.
Kim, U., S. Ghanbari, A. Ravikumar, J. Seubert, and S. Figueira. Rapid, affordable, and point-of-care water monitoring via a microfluidic DNA sensor and a mobile interface for global health. IEEE J. Transl. Eng. Health Med. 1:1–7, 2013.
Kim, J., M. Johnson, P. Hill, and B. K. Gale. Microfluidic sample preparation: cell lysis and nucleic acid purification. Integr. Biol. 1:574, 2009.
Kirsch, J., C. Siltanen, Q. Zhou, A. Revzin, and A. Simonian. Biosensor technology: recent advances in threat agent detection and medicine. Chem. Soc. Rev. 42:8733–8768, 2013.
Krüger, J., K. Singh, A. O’Neill, C. Jackson, A. Morrison, and P. O’Brien. Development of a microfluidic device for fluorescence activated cell sorting. J. Micromechanics Microengineering 12:486, 2002.
Landers, K. A., M. J. Burger, M. A. Tebay, D. M. Purdie, B. Scells, H. Samaratunga, M. F. Lavin, and R. A. Gardiner. Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int. J. Cancer 114:950–956, 2005.
Lillehoj, P. B., M.-C. Huang, N. Truong, and C.-M. Ho. Rapid electrochemical detection on a mobile phone. Lab. Chip 13:2950–2955, 2013.
Liu, J., M. Enzelberger, and S. Quake. A nanoliter rotary device for polymerase chain reaction. Electrophoresis 23:1531–1536, 2002.
Llovet, J. M., and J. Bruix. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48:1312–1327, 2008.
Market Research Report – point of care testing market to reach $25 billion by 2016. http://finance.yahoo.com/news/market-research-report-point-care-080800154.html.
Martinez, A. W., S. T. Phillips, E. Carrilho, S. W. Thomas, H. Sindi, and G. M. Whitesides. Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal. Chem. 80:3699–3707, 2008.
Minogue, T. D., P. A. Rachwal, A. T. Hall, J. W. Koehler, and S. A. Weller. Cross institute evaluations of inhibitor resistant PCR reagents for direct testing of aerosol and blood samples containing biological warfare agent (BWA) DNA. Appl. Environ. Microbiol., 2013. doi:10.1128/AEM.03478-13.
Miranda, B. S., E. M. Linares, S. Thalhammer, and L. T. Kubota. Development of a disposable and highly sensitive paper-based immunosensor for early diagnosis of Asian soybean rust. Biosens. Bioelectron. 45:123–128, 2013.
Mothershed, E. A., and A. M. Whitney. Nucleic acid-based methods for the detection of bacterial pathogens: present and future considerations for the clinical laboratory. Clin. Chim. Acta 363:206–220, 2006.
Mushlin, A. I., H. S. Ruchlin, and M. A. Callahan. Costeffectiveness of diagnostic tests. The Lancet 358:1353–1355, 2001.
Navruz, I., A. F. Coskun, J. Wong, S. Mohammad, D. Tseng, R. Nagi, S. Phillips, and A. Ozcan. Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array. Lab. Chip 13:4015–4023, 2013.
Niemz, A., T. M. Ferguson, and D. S. Boyle. Point-of-care nucleic acid testing for infectious diseases. Trends Biotechnol. 29:240–250, 2011.
Oncescu, V., D. O’Dell, and D. Erickson. Smartphone based health accessory for colorimetric detection of biomarkers in sweat and saliva. Lab. Chip 13:3232–3238, 2013.
Park, T. S., W. Li, K. E. McCracken, and J.-Y. Yoon. Smartphone quantifies Salmonella from paper microfluidics. Lab. Chip 13:4832–4840, 2013.
Petersen, C. L., T. P. Chen, J. M. Ansermino, and G. A. Dumont. Design and evaluation of a low-cost smartphone pulse oximeter. Sensors 13:16882–16893, 2013.
Price, C. W., D. C. Leslie, and J. P. Landers. Nucleic acid extraction techniques and application to the microchip. Lab. Chip 9:2484, 2009.
Ryuzakir, M., H. Nakamoto, S. Kinoshita, M. Sone, E. Nishida, H. Suzuki, and H. Itoh. 866 home blood pressure comparataive study between telmisartan plus hydrochlorothiazide vs. amlodipine using telemedicine blood pressure monitoring system. J. Hypertens. 30:e253, 2012.
Shah, P., X. Zhu, and C. Li. Development of paper-based analytical kit for point-of-care testing. Expert Rev. Mol. Diagn. 13:83–91, 2013.
Sidransky, D. Nucleic acid-based methods for the detection of cancer. Science 278:1054–1058, 1997.
Soper, S. A., K. Brown, A. Ellington, B. Frazier, G. Garcia-Manero, V. Gau, S. I. Gutman, D. F. Hayes, B. Korte, J. L. Landers, D. Larson, F. Ligler, A. Majumdar, M. Mascini, D. Nolte, Z. Rosenzweig, J. Wang, and D. Wilson. Point-of-care biosensor systems for cancer diagnostics/prognostics. Biosens. Bioelectron. 21:1932–1942, 2006.
Stedtfeld, R. D., D. M. Tourlousse, G. Seyrig, T. M. Stedtfeld, M. Kronlein, S. Price, F. Ahmad, E. Gulari, J. M. Tiedje, and S. A. Hashsham. Gene-Z: a device for point of care genetic testing using a smartphone. Lab. Chip 12:1454–1462, 2012.
Stemple, C. C., S. V. Angus, T. S. Park, and J.-Y. Yoon. Smartphone-based optofluidic lab-on-a-chip for detecting pathogens from blood. J. Lab. Autom. 19:35–41, 2014.
Strommer, E., J. Kaartinen, J. Parkka, A. Ylisaukko-oja, and I. Korhonen. Application of near field communication for health monitoring in daily life. 2006. doi:10.1109/IEMBS.2006.260021.
Tachakra, S., X. H. Wang, R. S. H. Istepanian, and Y. H. Song. Mobile e-health: the unwired evolution of telemedicine. Telemed. J. E Health 9:247–257, 2003.
Tahat, A. A. Mobile personal electrocardiogram monitoring system and transmission using MMS, 2008. doi:10.1109/ICCDCS.2008.4542630.
Thornton, C. R., and O. E. Wills. Immunodetection of fungal and oomycete pathogens: established and emerging threats to human health, animal welfare and global food security. Crit. Rev. Microbiol. 1–25, 2013. doi:10.3109/1040841X.2013.788995.
Tomita, N., Y. Mori, H. Kanda, and T. Notomi. Loop-mediated isothermal amplification (LAMP) of gene sequences and simple visual detection of products. Nat. Protoc. 3:877–882, 2008.
Tseng, D., O. Mudanyali, C. Oztoprak, S. O. Isikman, I. Sencan, O. Yaglidere, and A. Ozcan. Lensfree microscopy on a cellphone. Lab. Chip 10:1787–1792, 2010.
Vasudev, A., A. Kaushik, K. Jones, and S. Bhansali. Prospects of low temperature co-fired ceramic (LTCC) based microfluidic systems for point-of-care biosensing and environmental sensing. Microfluid. Nanofluidics 14:683–702, 2013.
Von Lode, P. Point-of-care immunotesting: approaching the analytical performance of central laboratory methods. Clin. Biochem. 38:591–606, 2005.
Wei, Q., H. Qi, W. Luo, D. Tseng, S. J. Ki, Z. Wan, Z. Göröcs, L. A. Bentolila, T–. T. Wu, R. Sun, and A. Ozcan. Fluorescent imaging of single nanoparticles and viruses on a smart phone. ACS Nano 7:9147–9155, 2013.
Wild, D. G. The Immunoassay Handbook: Theory and Applications of Ligand Binding, ELISA and Related Techniques. Oxford: Newnes, 2013, 1038 pp.
Wojtczak, J., and P. Bonadonna. Pocket mobile smartphone system for the point-of-care submandibular ultrasonography. Am. J. Emerg. Med. 31:573–577, 2013.
Wolcott, M. J. Advances in nucleic acid-based detection methods. Clin. Microbiol. Rev. 5:370–386, 1992.
Woodward, B., R. S. H. Istepanian, and C. I. Richards. Design of a telemedicine system using a mobile telephone. IEEE Trans. Inf. Technol. Biomed. 5:13–15, 2001.
Worldwide Quarterly Mobile Phone Tracker, 2011. http://www.idc.com/.
Zhang, R. Q., S. L. Liu, W. Zhao, W. P. Zhang, X. Yu, Y. Li, A. J. Li, D. W. Pang, and Z. L. Zhang. A simple point-of-care microfluidic immunomagnetic fluorescence assay for pathogens. Anal. Chem. 85:2645–2651, 2013.
Zhu, H., S. Mavandadi, A. F. Coskun, O. Yaglidere, and A. Ozcan. Optofluidic fluorescent imaging cytometry on a cell phone. Anal. Chem. 83:6641–6647, 2011.
Zhu, H., and A. Ozcan. Wide-field fluorescent microscopy and fluorescent imaging flow cytometry on a cell-phone. J. Vis. Exp. 2013. doi:10.3791/50451.
Zhu, H., I. Sencan, J. Wong, S. Dimitrov, D. Tseng, K. Nagashima, and A. Ozcan. Cost-effective and rapid blood analysis on a cell-phone. Lab. Chip 13:1282–1288, 2013.
Zhu, H., U. Sikora, and A. Ozcan. Quantum dot enabled detection of Escherichia coli using a cell-phone. Analyst 137:2541–2544, 2012.
Acknowledgments
We thank Carley Henke for her assistance in reviewing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Tingrui Pan oversaw the review of this article.
Rights and permissions
About this article
Cite this article
Liu, X., Lin, TY. & Lillehoj, P.B. Smartphones for Cell and Biomolecular Detection. Ann Biomed Eng 42, 2205–2217 (2014). https://doi.org/10.1007/s10439-014-1055-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-014-1055-z