Skip to main content
SpringerLink
Log in

Current Trends in Ligand Binding Real-Time Measurement Technologies

  • Review Article
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Numerous advances in ligand binding assay (LBA) real-time measurement technologies have been made within the last several years, ranging from the development of novel platforms to drive technology expansion to the adaptation of existing platforms to optimize performance and throughput. In this review, we have chosen to focus on technologies that provide increased value to two distinct segments of the LBA community. First, experimentally, by measuring real-time binding events, these technologies provide data that can be used to interrogate receptor/ligand binding interactions. While overall the platforms are not new, they have made significant advances in throughput, multiplexing, and/or sensitivity. Second, clinically, these point-of-care (POC) technologies provide instantaneous information which facilitates rapid treatment decisions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Nguyen HH, Park J, Kang S, Kim M. Surface plasmon resonance: a versatile technique for biosensor applications. Sensors. 2015;15(5):10481–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guo X. Surface plasmon resonance based biosensor technique: a review. J Biophotonics. 2012;5(7):483–501.

    Article  CAS  PubMed  Google Scholar 

  3. Maynard JA, Lindquist NC, Sutherland JN, Lesuffleur A, Warrington AE, Rodriguez M, et al. Surface plasmon resonance for high-throughput ligand screening of membrane-bound proteins. Biotechnol J. 2009;4(11):1542–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Phillips KS, Cheng Q. Recent advances in surface plasmon resonance based techniques for bioanalysis. Anal Bioanal Chem. 2007;387(5):1831–40.

    Article  CAS  PubMed  Google Scholar 

  5. Mariani S, Minunni M. Surface plasmon resonance applications in clinical analysis. Anal Bioanal Chem. 2014;406(9–10):2303–23.

    Article  CAS  PubMed  Google Scholar 

  6. Schmidt TP, Perna AM, Fugmann T, Bohm M, Jan H, Haller S, et al. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA. Sci Rep. 2016;6:23264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tarasov A, Gray DW, Tsai MY, Shields N, Montrose A, Creedon N, et al. A potentiometric biosensor for rapid on-site disease diagnostics. Biosens Bioelectron. 2016;79:669–78.

    Article  CAS  PubMed  Google Scholar 

  8. Fischer C, Hunniger T, Jarck JH, Frohnmeyer E, Kallinich C, Haase I, et al. Food sensing: aptamer-based trapping of Bacillus cereus spores with specific detection via real time PCR in milk. J Agric Food Chem. 2015;63(36):8050–7.

    Article  CAS  PubMed  Google Scholar 

  9. Altintas Z, Gittens M, Guerreiro A, Thompson KA, Walker J, Piletsky S, et al. Detection of waterborne viruses using high affinity molecularly imprinted polymers. Anal Chem. 2015;87(13):6801–7.

    Article  CAS  PubMed  Google Scholar 

  10. Fraser S, Cameron M, O'Connor E, Schwickart M, Tanen M, Ware M. Next generation ligand binding assays-review of emerging real-time measurement technologies. AAPS J. 2014;16(5):914–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chardin H, Mercier K, Frydman C, Vollmer N. Surface plasmon resonance imaging: a method to measure the affinity of the antibodies in allergy diagnosis. J Immunol Methods. 2014;405:23–8.

    Article  CAS  PubMed  Google Scholar 

  12. Vance S, Zeidan E, Henrich VC, Sandros MG. Comparative analysis of human growth hormone in serum using SPRi, nano-SPRi and ELISA assays. Journal of visualized experiments : JoVE. 2016;107

  13. Vance SA, Sandros MG. Zeptomole detection of C-reactive protein in serum by a nanoparticle amplified surface plasmon resonance imaging aptasensor. Sci Rep. 2014;4:5129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sage J, Mallevre F, Barbarin-Costes F, Samsonov SA, Gehrcke JP, Pisabarro MT, et al. Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity. Biochemistry. 2013;52(37):6487–98.

    Article  CAS  PubMed  Google Scholar 

  15. Melaine F, Roupioz Y, Buhot A. Gold nanoparticles surface plasmon resonance enhanced signal for the detection of small molecules on split-aptamer microarrays (small molecules detection from split-aptamers). Microarrays. 2015;4(1):41.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Boozer C, Kim G, Cong S, Guan H, Londergan T. Looking towards label-free biomolecular interaction analysis in a high-throughput format: a review of new surface plasmon resonance technologies. Curr Opin Biotechnol. 2006;17(4):400–5.

    Article  CAS  PubMed  Google Scholar 

  17. Ostuni E, Chapman RG, Holmlin RE, Takayama S, Whitesides GM. A survey of structure−property relationships of surfaces that resist the adsorption of protein. Langmuir: the ACS journal of surfaces and colloids. 2001;17(18):5605–20.

    Article  CAS  Google Scholar 

  18. Helmerhorst E, Chandler DJ, Nussio M, Mamotte CD. Real-time and label-free bio-sensing of molecular interactions by surface plasmon resonance: a laboratory medicine perspective. The Clinical Biochemist Reviews. 2012;33(4):161.

    PubMed  PubMed Central  Google Scholar 

  19. Wegener J, Janshoff A, Steinem C. The quarts crystal microbalance as a novel means to study cell-substrate interactions in situ. Cell Biochem Biophys. 2001;34:121–51.

    Article  CAS  PubMed  Google Scholar 

  20. Cathy I, Cheng Y-P, Ca Y-HC. Biomoleuclar interactions and tools for their recognition: focus on the quartz crystal microblalance and its diverse surface chemistries and applications. ChemSocRev. 2012;41:1947–71.

    Google Scholar 

  21. Dixon MC. Quartz crystal microbalance with dissipation monitoring: enabling real-time characterization of biological materials and their interactions. J Biomol Tech. 2008;19:151–8.

    PubMed  PubMed Central  Google Scholar 

  22. Salanti A, Clausen TM, Agerbaek MO, Al Nakouzi N, Dahlback M, Oo HZ, et al. Targeting human cancer by a glycosaminoglycan binding malaria protein. Cancer Cell. 2015;28(4):500–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Peiris D, Markiv A, Curley PG, Dwek M. A novel approach to determining the affinity of protein-carbohydrate interactions employing adherent cancer cells grown on a biosensor surface. Biosens Bioelectron. 2012;35:160–6.

    Article  CAS  PubMed  Google Scholar 

  24. Chen M-X, Chen J-X, Chen S-H, Huang D-N, Ai L, Zhang R-L. Development of lateral flow immunoassay for antigen detection in human Angiostrongylus cantonensis infection. Korean J Parasitol. 2016;54(3):375–80.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jawaid W, Campbell K, Melville K, Holmes SJ, Rice J, Elliott CT. Development and validation of a novel lateral flow immunoassay (LFIA) for the rapid screening of paralytic shellfish toxins (PSTs) from shellfish extracts. Anal Chem. 2015;87(10):5324–32.

    Article  CAS  PubMed  Google Scholar 

  26. Nagatani N, Yamanaka K, Ushijima H, Koketsu R, Sasaki T, Ikuta K, et al. Detection of influenza virus using a lateral flow immunoassay for amplified DNA by a microfluidic RT-PCR chip. Analyst. 2012;137(15):3422–6.

    Article  CAS  PubMed  Google Scholar 

  27. Zhu J, Zou N, Mao H, Wang P, Zhu D, Ji H, et al. Evaluation of a modified lateral flow immunoassay for detection of high-sensitivity cardiac troponin I andmyoglobin. Biosens Bioelectron. 2013;42:522–5.

    Article  CAS  PubMed  Google Scholar 

  28. Plotz CM, Singer JM. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Am J Med. 1956;21(6):888–92.

    Article  CAS  PubMed  Google Scholar 

  29. Taranova N, Byzova N, Zaiko V, Starovoitova T, Vengerov Y, Zherdev A, Dzantiev B. Integration of lateral flow and microarray technologies for multiplex immunoassay: application to the determination of drugs of abuse. Microchim Acto. 2013;180:1165–72.

    Article  CAS  Google Scholar 

  30. Fong WK, Modrusan Z, McNevin JP, Marostenmaki J, Zin B, Bekkaoui F. Rapid solid-phase immunoassay for detection of methicillin-resistant Staphylococcus aureus using cycling probe technology. J Clin Microbiol. 2000;38(7):2525–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Edwards KA, Baeumner AJ. Optimization of DNA-tagged dye-encapsulating liposomes for lateral-flow assays based on sandwich hybridization. Anal Bioanal Chem. 2006;386(5):1335–43.

    Article  CAS  PubMed  Google Scholar 

  32. Connelly JT, Nugen SR, Borejsza-Wysocki W, Durst RA, Montagna RA, Baeumner AJ. Human pathogenic Cryptosporidium species bioanalytical detection method with single oocyst detection capability. Anal Bioanal Chem. 2008;391(2):487–95.

    Article  CAS  PubMed  Google Scholar 

  33. Kalogianni DP, Goura S, Aletras AJ, Christopoulos TK, Chanos MG, Christofidou M, et al. Dry reagent dipstick test combined with 23S rRNA PCR for molecular diagnosis of bacterial infection in arthroplasty. Anal Biochem. 2007;361(2):169–75.

    Article  CAS  PubMed  Google Scholar 

  34. Hansen J, Slechta ES, Gates-Hollingsworth MA, Neary B, Barker AP, Bauman S, et al. Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid. Clinical and vaccine immunology: CVI. 2013;20(1):52–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. McDonnell B, Hearty S, Leonard P, O'Kennedy R. Cardiac biomarkers and the case for point-of-care testing. Clin Biochem. 2009;42(7–8):549–61.

    Article  CAS  PubMed  Google Scholar 

  36. Vaidya VS, Ford GM, Waikar SS, Wang Y, Clement MB, Ramirez V, et al. A rapid urine test for early detection of kidney injury. Kidney Int. 2009;76(1):108–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Miano R, Mele GO, Germani S, Bove P, Sansalone S, Pugliese PF, et al. Evaluation of a new, rapid, qualitative, one-step PSA test for prostate cancer screening: the PSA RapidScreen test. Prostate Cancer Prostatic Dis. 2005;8(3):219–23.

    Article  CAS  PubMed  Google Scholar 

  38. Barnett JM, Wraith P, Kiely J, Persad R, Hurley K, Hawkins P, et al. An inexpensive, fast and sensitive quantitative lateral flow magneto-immunoassay for total prostate specific antigen. Biosensors. 2014;4(3):204–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, Halloran SP, et al. Advances in fecal occult blood tests: the FIT revolution. Dig Dis Sci. 2015;60(3):609–22.

    Article  PubMed  Google Scholar 

  40. Cho IH, Seo SM, Paek EH, Paek SH. Immunogold-silver staining-on-a-chip biosensor based on cross-flow chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878(2):271–7.

    Article  CAS  PubMed  Google Scholar 

  41. van Amerongen A, Wichers JH, Berendsen LB, Timmermans AJ, Keizer GD, van Doorn AW, et al. Colloidal carbon particles as a new label for rapid immunochemical test methods: quantitative computer image analysis of results. J Biotechnol. 1993;30(2):185–95.

    Article  PubMed  Google Scholar 

  42. Linares EM, Kubota LT, Michaelis J, Thalhammer S. Enhancement of the detection limit for lateral flow immunoassays: evaluation and comparison of bioconjugates. J Immunol Methods. 2012;375(1–2):264–70.

    Article  CAS  PubMed  Google Scholar 

  43. Sun K, Xing W, Yu X, Fu W, Wang Y, Zou M, et al. Recombinase polymerase amplification combined with a lateral flow dipstick for rapid and visual detection of Schistosoma japonicum. Parasit Vectors. 2016;9:476.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Worbs S, Skiba M, Bender J, Zeleny R, Schimmel H, Luginbuhl W, et al. An international proficiency test to detect, identify and quantify ricin in complex matrices. Toxins. 2015;7(12):4987–5010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stojanovic I, Schasfoort RB, Terstappen LW. Analysis of cell surface antigens by surface plasmon resonance imaging. Biosens Bioelectron. 2014;52:36–43.

    Article  CAS  PubMed  Google Scholar 

  46. Stojanovic I, van der Velden TJ, Mulder HW, Schasfoort RB, Terstappen LW. Quantification of antibody production of individual hybridoma cells by surface plasmon resonance imaging. Anal Biochem. 2015;485:112–8.

    Article  CAS  PubMed  Google Scholar 

  47. Gong C, Zeng J, Akinsanya B, Jiang H, Mora J, Chilewski S, et al. Development and validation of an LC-MS/MS assay for the quantitation of a PEGylated anti-CD28 domain antibody in human serum: overcoming interference from antidrug antibodies and soluble target. Bioanalysis. 2014;6(18):2371–83.

    Article  CAS  PubMed  Google Scholar 

  48. Dong H, Mora JR, Brockus C, Chilewski SD, Dodge R, Merrifield C, et al. Development of a generic anti-PEG antibody assay using BioScale’s Acoustic Membrane MicroParticle technology. AAPS J. 2015;17(6):1511–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pfizer, Eastern Point Rd, Groton, Connecticut, 06340, USA

    Stephanie Fraser

  2. Amgen Inc., One Amgen Center Drive, Thousand Oaks, California, 91320, USA

    Judy Y. Shih

  3. Janssen Research & Development, LLC, 1400 McKean Road, Spring House, Pennsylvania, 19477, USA

    Mark Ware

  4. AegisBioconsult, 78 Marbern Dr., Suffield, Connecticut, 06078, USA

    Edward O’Connor

  5. Lumigen, 22900 8 Mile Road, Southfield, Michigan, 48033, USA

    Mark J. Cameron

  6. MedImmune, 319 N. Bernardo Ave, Mountain View, California, 94043, USA

    Martin Schwickart

  7. Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Xuemei Zhao

  8. Boehringer Ingelheim, 6701 Kaiser Drive, Fremont, California, 94555, USA

    Karin Regnstrom

Authors
  1. Stephanie Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judy Y. Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Ware
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edward O’Connor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark J. Cameron
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martin Schwickart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuemei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karin Regnstrom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephanie Fraser.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fraser, S., Shih, J., Ware, M. et al. Current Trends in Ligand Binding Real-Time Measurement Technologies. AAPS J 19, 682–691 (2017). https://doi.org/10.1208/s12248-017-0067-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-017-0067-7

KEY WORDS

Search

Navigation