Skip to main content
Log in

Blister pouches for effective reagent storage on microfluidic chips for blood cell counting

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

We present the analysis of blister pouches for reagent storage and release into microfluidic devices towards point-of-care blood cell counting applications. Blister pouches provide an effective reagent storage mechanism and can be mounted onto microfluidic cartridges directly. Reagents can be released from blister pouches through automated or manual compression and consequent rupturing of the pouches. A microfluidic device for metering of blister pouch contents was developed and investigated as part of this work, as precise volumes of reagents are often required when performing reactions, and particularly for blood cell counting applications which are the focus of this study. The metering device shows high accuracy and repeatability with an error of 1.93% and standard deviation of 3.1% across 30 test results. This work also investigates important blister pouch characteristics for three different types of blister pouch foil materials, including forces required to burst the blister, as well as shelf life and reagent compatibility of the blisters. Typical forces required are in the range of 25–35 N depending on the blister foil material used. Blister shelf life can be greatly affected by the reagent being stored, and thus, the blister foil material choice is crucial. This work provides a clear understanding of the implementation required to ensure that the blister pouches can be effectively used on microfluidic chips, with an example application area being point-of-care diagnostics.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15

Similar content being viewed by others

References

  • Abbott Laboratories (2015) i-Stat® Test Cartridges, Abbott Point of Care, viewed 20 April 2016. https://www.abbottpointofcare.com/products-services/istat-test-cartridges

  • Bau HH, Liu C, Qiu X (2010) Biodetection cassette with automated actuator. US Patent US20100035349 A1

  • Becker H (2009) Hype, hope and hubris: the quest for the killer application in microfluidics. Lab Chip 9:2119–2122. doi:10.1039/B911553F

    Article  Google Scholar 

  • Becker H, Gärtner C (2008) Polymer microfabrication technologies for microfluidic systems. Anal Bioanal Chem 390(1):89–111

    Article  Google Scholar 

  • Bozhi Y, Levis JW, Qiao L (2004) A PDMS-based constant-flowrate microfluidic control device. In: Proceedings of 17th IEEE international conference on micro electro mechanical systems (MEMS), pp 379–382

  • Chen D, Bau HH, Mauk MG, Qiu X, Kwa J (2010a) Mechanically actuated diagnostic device. US Patent US20100304986 A1

  • Chen D, Mauk M, Qiu X, Liu C, Kim J, Ramprasad S, Ongagna S, Abrams WR, Malamud D, Corstjens PL, Bau HH (2010b) An integrated, self-contained microfluidic cassette for isolation, amplification, and detection of nucleic acids. Biomed Microdevices 12(4):705–719

    Article  Google Scholar 

  • Chin CD, Linder V, Sia SK (2007) Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip 7:41–57

    Article  Google Scholar 

  • Chin CD, Linder V, Sia SK (2012) Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip 12:2118–2134

    Article  Google Scholar 

  • Czurratis D, Beyl Y, Grimm A, Brettschneider T, Zinober S, Laermer F, Zengerle R (2015) Liquids on-chip: direct storage and release employing micro-perforated vapor barrier films. Lab Chip 15:2887–2895

    Article  Google Scholar 

  • Daktari Diagnostics (2015) viewed on 20 April 2016. http://daktaridx.com/

  • Findlay JB, Atwood SM, Bergmeyer L, Chemelli J, Christy K, Cummins T, Donish W, Ekeze T, Falvo J, Patterson D (1993) Automated closed-vessel system for in vitro diagnostics based on polymerase chain reaction. Clin Chem 39(9):1927–1933

    Google Scholar 

  • Focke M, Kosse D, Muller C, Reinecke H, Zengerle T, von Stetten F (2010) Lab on a foil: microfluidcs on thin and flexible films. Lab Chip 10:1365–1386. doi:10.1039/c001195a

    Article  Google Scholar 

  • Giselbrecht S, Gietzelt T, Gottwald E, Guber AE, Trautmann C, Truckenmüller R, Weibezahn KF (2004) Microthermoforming as a novel technique for manufacturing scaffolds in tissue engineering (CellChips). IEE Proc Nanobiotechnol 151(4):151–157

    Article  Google Scholar 

  • Gomez FA (2013) The future of microfluidic point-of-care diagnostic devices. Bioanalysis 5:1–3

    Article  Google Scholar 

  • Hitzbleck M, Delamarche E (2013) Reagents in microfluidics: an “in” and “out” challenge. Chem Soc Rev 42:8494–8516

    Article  Google Scholar 

  • Hugo S, Land K, Becker H (2013) Characterization of microfluidic components for low-cost point-of-care devices. In: Proceedings of 17th international conference on miniaturized systems for chemistry and life sciences, pp 461–463

  • Inamdar T, Anthony BW (2013) Characterizing fluidic seals for on-board reagent delivery. In: Proceedings of SPIE 8615 microfluidics BioMEMS and medical microsystems XI, p 861516. doi:10.1117/12.2006257

  • Jangam SR, Agarwal AK, Sur K, Kelso DM (2013) A point-of-care PCR test for HIV-1 detection in resource-limited settings. Biosens Bioelectron 42:69–75

    Article  Google Scholar 

  • Jokerst JV, Floriano PN, Christodoulides N, Simmons GW, McDevitt JT (2008) Integration of semiconductor quantum dots into nano-bio-chip systems for enumeration of CD4+ T cell counts at the point-of-need. Lab Chip 8(12):2079–2090

    Article  Google Scholar 

  • Jokerst JV, Jacobson JW, Bhagwandin BD, Floriano PN, Christodoulides N, McDevitt JT (2010) Programmable nano-bio-chip sensors: analytical meets clinical. Anal Chem 82(5):1571–1579

    Article  Google Scholar 

  • Jung W, Han J, Choi JW, Ahn CH (2015) Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies. Microelectron Eng 132:46–57

    Article  Google Scholar 

  • Kelso DM, Agarwal AK, Sur K, Beebe DJ (2012) Burstable liquid packaging and uses thereof. US Patent US2012010781 A1

  • Kim J, Johnson M, Hill P, Gale BK (2009) Microfluidic sample preparation: cell lysis and nucleic acid purification. Integr Biol 1:574–586

    Article  Google Scholar 

  • Lauks IR, Wieck HJ, Zelin MP, Blyskal P (1988) Disposable sensing device for real time fluid analysis. US Patent US5096669 A

  • Lewis SM, Bain BJ, Bates I (2006) Dacie and Lewis practical haematology. Churchill Livingstone, Philadelphia

    Google Scholar 

  • McDevitt J, Haque A, McRae M, Simmons G (2015) Integrated instrumentation for the analysis of biofluids at the point-of-care. US Patent US20150004717 A1

  • Osei-Bimpong A, Jury C, McLean R, Lewis SM (2009) Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device. Int J Lab Hematol 31(6):657–664

    Article  Google Scholar 

  • Pilchik R (2000) Pharmaceutical blister packaging, Part I. Rationale and materials. Pharm Technol 24(11):68–78

    Google Scholar 

  • Qiu X, Thompson JA, Chen Z, Liu C, Chen D, Ramprasad S, Mauk MG, Ongagna S, Barber C, Abrams WR, Malamud D (2009) Finger-actuated, self-contained immunoassay cassettes. Biomed Microdevices 11(6):1175–1186

    Article  Google Scholar 

  • Qiu X, Liu C, Mauk MG, Hart RW, Chen D, Qiu J, Kientz T, Fiene J, Bau HH (2011) A portable analyzer for pouch-actuated, immunoassay cassettes. Sens Actuators B Chem 160(1):1529–1535

    Article  Google Scholar 

  • Selvakumar S, Linares R, Oppenheimer A, Anthony B (2012) Variation analysis of flow rate delivered using a blister pump. In: Proceedings of SPIE 8251 microfluidics BioMEMS and medical microsystems X, p 82510I

  • Sia SK, Kricka LJ (2008) Microfluidics and point-of-care testing. Lab Chip 8:1982–1983

    Article  Google Scholar 

  • Simmons GW, McRae MP, Shadfan B, Wong J, Christodoulides N, Ruijven PWMV, Hayes JP, Mehalso R, McDevitt JT (2014) Programmable bio-nano-chip system: an ultra-flexible platform for bioscience and clinical measurements. In: Proceedings of 18th international conference on miniaturized systems for chemistry and life sciences, pp 2059–2063

  • Smith S, Naidoo T, Davies E, Fourie L, Nxumalo Z, Swart H, Marais P, Land K, Roux P (2015) Sample to answer visualization pipeline for low-cost point-of-care blood cell counting. In: Proceedings of SPIE 9332 optical diagnostics and sensing XV: towards point-of-care diagnostics, p 93320V

  • Smith S, Sewart R, Land K, Roux P, Gärtner C, Becker H (2016) Blister technology for the storage of liquid reagents in microfluidic devices. In: Proceedings of SPIE 9705 microfluidics BioMEMS and medical microsystems XIV, p 97050F

  • Temiz Y, Lovchik RD, Kaigala GV, Delamarche E (2015) Lab-on-a-chip devices: how to close and plug the lab. Microelectron Eng 132:156–175

    Article  Google Scholar 

  • van Oordt T, Barb Y, Smetana J, Zengerle R, von Stetten F (2013) Miniature stick-packaging—an industrial technology for pre-storage and release of reagents in lab-on-a-chip systems. Lab Chip 13(15):2888–2892

    Article  Google Scholar 

  • Weaver W, Kittur H, Dhar M, Di Carlo D (2014) Research highlights: microfluidic point-of-care diagnostics. Lab Chip 14:1962–1965

    Article  Google Scholar 

  • Weber L (2015) Microfluidic storage device. US Patent US9211538 B2

  • Wright DW, Aiello D (2014) Apparatus, devices, and methods for manipulating deformable fluid vessels. US Patent US20140263437 A1

  • Yager P, Edwards T, Fu E, Helton K, Nelson K, Tam M, Weigl B (2006) Microfluidic diagnostic technologies for global public health. Nature 442:412–418

    Article  Google Scholar 

  • Yetisen AK, Volpatti LR (2014) Patent protection and licensing in microfluidics. Lab Chip 14:2217–2225

    Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the Council for Scientific and Industrial Research (CSIR) in Pretoria, South Africa, for funding this project. Part of the work carried out at microfluidic ChipShop GmbH was financially supported by the European Union in an FP-7 Grant under the project “Routine”, Grant Agreement No. 304941, by the Bundesministerium für Bildung und Forschung (BMBF) through the Project “IMRA”, FKZ: 031A094C and the Project “MRCyte”, FZK 13N12018. The authors thank all project partners for their contributions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suzanne Smith.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smith, S., Sewart, R., Becker, H. et al. Blister pouches for effective reagent storage on microfluidic chips for blood cell counting. Microfluid Nanofluid 20, 163 (2016). https://doi.org/10.1007/s10404-016-1830-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10404-016-1830-2

Keywords

Navigation