A cell-based biosensor for real-time detection of cardiotoxicity using lensfree imaging.

Sang Bok Kim, Hojae Bae, Jae Min Cha, Sang Jun Moon, Mehmet R Dokmeci, Donald M Cropek, Ali Khademhosseini
Author Information
  1. Sang Bok Kim: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

A portable and cost-effective real-time cardiotoxicity biosensor was developed using a CMOS imaging module extracted from a commercially available webcam. The detection system consists of a CMOS imaging module, a white LED and a pinhole. Real-time image processing was conducted by comparing reference and live frame images. To evaluate the engineered system, the effects of two different drugs, isoprenaline and doxorubicin, on the beating rate and beat-to-beat variations of ESC-derived cardiomyocytes were measured. The detection system was used to conclude that the beat-to-beat variability increased under treatment with both isoprenaline and doxorubicin. However, the beating rates increased upon the addition of isoprenaline but decreased for cultures supplemented with doxorubicin. Moreover, the response time for both the beating rates and the beat-to-beat variability of ESC-derived cardiomyocytes under treatment of isoprenaline was shorter than for doxorubicin, although the amount of isoprenaline used in the measurement was three orders of magnitude lower than that of doxorubicin. Given its ability to perform real-time cell monitoring in a simple and inexpensive manner, the proposed system may be useful for a range of cell-based biosensing applications.

References

  1. Trends Biotechnol. 2009 Mar;27(3):179-88 [PMID: 19187988]
  2. Nat Med. 2006 Aug;12(8):908-16 [PMID: 16862153]
  3. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15340-4 [PMID: 20798064]
  4. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10670-5 [PMID: 18663227]
  5. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16978-83 [PMID: 19805103]
  6. Assay Drug Dev Technol. 2008 Jun;6(3):375-85 [PMID: 18532900]
  7. Eur J Pharmacol. 2002 Jun 7;445(1-2):1-12 [PMID: 12065188]
  8. Lab Chip. 2010 Apr 7;10(7):824-7 [PMID: 20379564]
  9. Biosens Bioelectron. 2010 Dec 15;26(4):1493-9 [PMID: 20732805]
  10. Drug Discov Today. 2008 Sep;13(17-18):778-84 [PMID: 18617014]
  11. Pharmacogenomics. 2006 Sep;7(6):889-908 [PMID: 16981848]
  12. Circ Res. 2002 Aug 9;91(3):189-201 [PMID: 12169644]
  13. Appl Phys Lett. 2010 Nov 29;97(22):221107 [PMID: 21203381]
  14. Drug Discov Today. 2008 Nov;13(21-22):989-96 [PMID: 18835363]
  15. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2480-7 [PMID: 16477028]
  16. Biosens Bioelectron. 1990;5(3):223-34 [PMID: 2206490]
  17. J Mol Med (Berl). 2009 Apr;87(4):401-10 [PMID: 19139834]
  18. Lab Chip. 2009 Mar 21;9(6):777-87 [PMID: 19255659]
  19. Nat Mater. 2005 Aug;4(8):622-8 [PMID: 16041377]
  20. Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:1060-3 [PMID: 19965137]
  21. Nat Med. 1999 Mar;5(3):331-4 [PMID: 10086391]
  22. Drug Discov Today. 2008 Jan;13(1-2):1-13 [PMID: 18190858]
  23. Biomaterials. 2008 Feb;29(6):752-63 [PMID: 18001830]
  24. Tissue Eng Part B Rev. 2009 Dec;15(4):443-54 [PMID: 19552604]
  25. Biochem Biophys Res Commun. 2009 Dec 25;390(4):1214-20 [PMID: 19878660]
  26. Angew Chem Int Ed Engl. 2002 Jul 2;41(13):2320-3 [PMID: 12203579]
  27. Am J Gastroenterol. 2008 Apr;103(4):815-9 [PMID: 18397418]
  28. Chem Res Toxicol. 2008 May;21(5):978-89 [PMID: 18376852]
  29. Lab Chip. 2010 Nov 21;10(22):3125-9 [PMID: 20877904]
  30. Crit Care Med. 2000 Oct;28(10 Suppl):N121-8 [PMID: 11055680]
  31. Biomed Microdevices. 2007 Apr;9(2):149-57 [PMID: 17146728]
  32. Biomed Microdevices. 2006 Sep;8(3):231-7 [PMID: 16732418]
  33. Biosens Bioelectron. 2007 Jun 15;22(12):3224-9 [PMID: 17416514]
  34. Biomaterials. 2006 Dec;27(36):5968-77 [PMID: 16901537]
  35. Opt Lett. 2004 May 15;29(10):1132-4 [PMID: 15182009]
  36. Biotechnol Bioeng. 2009 Feb 15;102(3):856-868 [PMID: 18853435]

Grants

  1. R01 HL092836-04/NHLBI NIH HHS
  2. R21 EB007249-02/NIBIB NIH HHS
  3. EB007249/NIBIB NIH HHS
  4. HL092836/NHLBI NIH HHS
  5. R21 EB009196/NIBIB NIH HHS
  6. EB009196/NIBIB NIH HHS
  7. DE019024/NIDCR NIH HHS
  8. R21 EB009196-02/NIBIB NIH HHS
  9. RL1 DE019024/NIDCR NIH HHS
  10. RL1 DE019024-04/NIDCR NIH HHS
  11. R21 EB007249/NIBIB NIH HHS
  12. R01 HL092836/NHLBI NIH HHS

MeSH Term

Animals
Biosensing Techniques
Doxorubicin
Embryonic Stem Cells
Image Processing, Computer-Assisted
Immunohistochemistry
Isoproterenol
Mice
Myocytes, Cardiac
Semiconductors
Time Factors
Toxicity Tests

Chemicals

Doxorubicin
Isoproterenol

Word Cloud

Created with Highcharts 10.0.0isoprenalinedoxorubicinsystemreal-timeimagingdetectionbeatingbeat-to-beatcardiotoxicitybiosensorusingCMOSmoduleESC-derivedcardiomyocytesusedvariabilityincreasedtreatmentratescell-basedportablecost-effectivedevelopedextractedcommerciallyavailablewebcamconsistswhiteLEDpinholeReal-timeimageprocessingconductedcomparingreferenceliveframeimagesevaluateengineeredeffectstwodifferentdrugsratevariationsmeasuredconcludeHoweveruponadditiondecreasedculturessupplementedMoreoverresponsetimeshorteralthoughamountmeasurementthreeordersmagnitudelowerGivenabilityperformcellmonitoringsimpleinexpensivemannerproposedmayusefulrangebiosensingapplicationslensfree

Similar Articles

Cited By