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Research Article

Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis

Rahim Esfandyarpour, Matthew J. DiDonato, Yuxin Yang, Naside Gozde Durmus, James S. Harris, and Ronald W. Davis
  1. aDepartment of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304;
  2. bStanford Genome Technology Center, Stanford University, Stanford, CA 94304;
  3. cSchool of Engineering, Stanford University, Stanford, CA 94304;
  4. dElectrical Engineering Department, Stanford University, Stanford, CA 94304

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PNAS February 21, 2017 114 (8) E1306-E1315; first published February 6, 2017; https://doi.org/10.1073/pnas.1621318114
Rahim Esfandyarpour
aDepartment of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304;
bStanford Genome Technology Center, Stanford University, Stanford, CA 94304;
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Matthew J. DiDonato
cSchool of Engineering, Stanford University, Stanford, CA 94304;
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Yuxin Yang
dElectrical Engineering Department, Stanford University, Stanford, CA 94304
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Naside Gozde Durmus
aDepartment of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304;
bStanford Genome Technology Center, Stanford University, Stanford, CA 94304;
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James S. Harris
dElectrical Engineering Department, Stanford University, Stanford, CA 94304
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Ronald W. Davis
aDepartment of Biochemistry, School of Medicine, Stanford University, Stanford, CA 94304;
bStanford Genome Technology Center, Stanford University, Stanford, CA 94304;
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  • For correspondence: jeanne.thompson@stanford.edu
  1. Contributed by Ronald W. Davis, December 28, 2016 (sent for review December 15, 2016; reviewed by Behrad Noudoost and Iman Rezanezhad Gatabi)

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Significance

Point-of-care diagnostics in the developing world and resource-limited areas require numerous special design considerations to provide effective early detection of disease. Of particular need for these contexts are diagnostic technologies featuring low costs, ease of use, and broad applicability. Here we present a nanoparticle-inkjet-printable microfluidics-based platform that fulfills these criteria and that we expect to significantly reduce the footprint, complexity, and cost of clinical diagnostics. This reusable $0.01 platform is miniaturized to handle small sample volumes and can perform numerous analyses. It can perform complex, minimally invasive analyses of single cells without specialized equipment and personnel. This inexpensive, accessible platform has broad applications in precision diagnostics and is a step toward the democratization of medical technologies.

Abstract

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra–low-cost, rapid, and miniaturized lab-on-a-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, time-consuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01—an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries.

  • lab on a chip
  • point of care
  • diagnostics
  • nanoparticles
  • microfluidics

Footnotes

  • ↵1To whom correspondence should be addressed. Email: jeanne.thompson{at}stanford.edu.
  • Author contributions: R.E., J.S.H., and R.W.D. designed research; R.E., M.J.D., and Y.Y. performed research; R.E., M.J.D., Y.Y., and N.G.D. contributed new reagents/analytic tools; R.E., M.J.D., Y.Y., and R.W.D. analyzed data; and R.E., M.J.D., and R.W.D. wrote the paper.

  • Reviewers: I.R.G., Cypress Semiconductor Corporation; and B.N., Montana State University.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1621318114/-/DCSupplemental.

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Multifunctional, inexpensive biochip
Rahim Esfandyarpour, Matthew J. DiDonato, Yuxin Yang, Naside Gozde Durmus, James S. Harris, Ronald W. Davis
Proceedings of the National Academy of Sciences Feb 2017, 114 (8) E1306-E1315; DOI: 10.1073/pnas.1621318114

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Multifunctional, inexpensive biochip
Rahim Esfandyarpour, Matthew J. DiDonato, Yuxin Yang, Naside Gozde Durmus, James S. Harris, Ronald W. Davis
Proceedings of the National Academy of Sciences Feb 2017, 114 (8) E1306-E1315; DOI: 10.1073/pnas.1621318114
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Proceedings of the National Academy of Sciences: 114 (8)
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