Inkjet-printed micro-calibration standards for ultraquantitative Raman spectral cytometry

Vernon LaLone; Maria V. Fawaz; Jomar Morales-Mercado; Márcio A. Mourão; Catherine S. Snyder; Sang Yeop Kim; Andrew P. Lieberman; Anish Tuteja; Geeta Mehta; Theodore J. Standiford; Krishnan Raghavendran; Kerby Shedden; Anna Schwendeman; Kathleen A. Stringer; Gus R. Rosania

doi:10.1039/C9AN00500E

Inkjet-printed micro-calibration standards for ultraquantitative Raman spectral cytometry†

Vernon LaLone,

*^a Maria V. Fawaz,

^b Jomar Morales-Mercado,

^c Márcio A. Mourão,

^d Catherine S. Snyder,

^e Sang Yeop Kim,

^a Andrew P. Lieberman,^f Anish Tuteja,

^eg Geeta Mehta,

^eh Theodore J. Standiford,

ⁱ Krishnan Raghavendran,

^j Kerby Shedden,

^d Anna Schwendeman,

^a Kathleen A. Stringer

^ik and Gus R. Rosania

*^a

Author affiliations

* Corresponding authors

^a Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA
E-mail: grosania@umich.edu
Tel: +1 734-763-1032

^b Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA

^c School of Sciences, Technology, and Environment, Universidad Ana G. Méndez Cupey Campus, San Juan, Puerto Rico

^d CSCAR Center, University of Michigan, Ann Arbor, MI 48109, USA

^e Department of Materials Science and Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA

^f Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA

^g Biointerfaces Institute, Macromolecular Science and Engineering, Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA

^h Department of Biomedical Engineering, Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA

ⁱ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA

^j Department of Surgery, Michigan Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA

^k Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA

Abstract

Herein we report the development of a cytometric analysis platform for measuring the contents of individual cells in absolute (picogram) scales; this study represents the first report of Raman-based quantitation of the absolute mass – or the total amount – of multiple endogenous biomolecules within single-cells. To enable ultraquantitative calibration, we engineered single-cell-sized micro-calibration standards of known composition by inkjet-printer deposition of biomolecular components in microarrays across the surface of silicon chips. We demonstrate clinical feasibility by characterizing the compositional phenotype of human skin fibroblast and porcine alveolar macrophage cell populations in the respective contexts of Niemann–Pick disease and drug-induced phospholipidosis: two types of lipid storage disorders. We envision this microanalytical platform as the foundation for many future biomedical applications, ranging from diagnostic assays to pathological analysis to advanced pharmaco/toxicokinetic research studies.

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Inkjet-printed micro-calibration standards for ultraquantitative Raman spectral cytometry†

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Inkjet-printed micro-calibration standards for ultraquantitative Raman spectral cytometry

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