No CrossRef data available.
Article contents
Optimizing Homogeneous Thin Solid Films (HTSFs) from µL-Blood Droplets via Hyper-Hydrophilic Coatings (HemaDropTM) for Accurate Compositional Analysis via IBA, XRF, and XPS
Published online by Cambridge University Press: 23 October 2019
Abstract
Liquid phase analysis dominates the field of blood diagnostics and requires drawing blood volumes of several ml for each test. To achieve acceptable accuracy, each single liquid blood test requires ∼7 mL per blood sample, and repeated blood tests are often needed. Frequent testing ca result in Hospital Acquired Anemia for infants, chronically ill, and critically ill patients. Blood testing methods that can be utilized with small amounts of blood are a critical need to save lives. Theranos claimed to have developed novel methods requiring only a few nL of blood. However, Theranos’ techniques led to errors that exceeded beyond the medically acceptable threshold of 10%. This work investigates solid state blood analysis using low volumes of several µL. The most common blood tests used as first line for diagnostics and monitoring patients’ status, always include blood electrolytes, iron, and in some cases, heavy metals.
The present work investigates the formation of rapidly solidified Homogeneous Thin Solid Films (HTSFs) formed from blood drops, in order to make them suitable for solid state analysis in vacuo and in air. The solidification of ∼5 micro-liter (µL)-sized blood droplets into HTSFs is studied with two goals: achieve reproducible HTSFs optimized for producing accurate analysis, and successfully measure the potential accuracy of measurements made on HTSFs for blood electrolytes Na, K, Mg, Ca, and Cl and heavy metals such as Fe.
The blood volumes selected for this work are in the µL range, one thousandth volumes drawn for current liquid phase analysis. Balanced Saline Solution (BSS) is used as an initial liquid for testing solidification uniformity and a potential calibration material. Next, canine and human blood are studied on two types of HemaDropTM coatings for solidification: super-hydrophilic and hyper-hydrophilic. HTSF formation from BSS and blood drops are compared on both coated and uncoated surfaces.
Three solid state analytical methods are investigated in parallel to probe composition at different depths and test each for reproducibility and accuracy: Ion Beam Analysis (IBA), X-ray Fluorescence (XRF), and X-ray Photoelectron Spectroscopy (XPS). The results show that using solid films of blood yields composition, which can be reproducibly measured by IBA, XPS and XRF to varying degrees. XPS’s depth of analysis, limited to ∼5 nm, probes a small fraction of the HTSF, but provides insights into the range of thickness for homogeneous compositions in HTSFs. Statistical and error analysis help establish whether measurements taken in sets of three typically used in lab fall below the medically accepted error threshold (<10%) for each technique and element detected. Measurements are repeated and taken at various locations and on different HTSFs to establish reproducibility. XRF is of particular interest, because it is fast, accurate, portable and can be conducted in air, making it ideal for areas with limited resources.
- Type
- Articles
- Information
- Copyright
- Copyright © Materials Research Society 2019
References
REFERENCES
Harris, A M, Atterbury, C L J, Chaffe, B, Elliott, C, Hawkins, T, Hennem, S J, Howell, C, Jones, J, Murray, S, New, H V, et al. Guideline on the Administration of Blood Components.Google Scholar
Arsie, M P, Marchioro, L, Lapolla, A, Giacchetto, G F, Bordin, M R, Rizzotti, P, and Fedele, D. Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring of HbA1c. Acta diabetologica, 37(1):1–7, 2000.CrossRefGoogle ScholarPubMed
Zhi, Ming, Ding, Eric L, Theisen-Toupal, Jesse, Whelan, Julia, and Arnaout, Ramy. The landscape of inappropriate laboratory testing: a 15-year meta-analysis. PloS one, 8(11): e78962, 2013.CrossRefGoogle ScholarPubMed
Buettner, J, Puser, S, et al. , editors. Senses, sensors, and systems: a journey through the history of laboratory diagnosis. F Hoffmann-La Roche & Co., Basel, Switzerland, 2004.Google Scholar
Van der Bom, J G and Cannegieter, S C. Hospital-acquired anemia: the contribution of diagnostic blood loss. Journal of Thrombosis and Haemostasis, 13(6):1157–1159, 2015.CrossRefGoogle ScholarPubMed
Salisbury, Adam C, Reid, Kimberly J, Alexander, Karen P, Masoudi, Frederick A, Lai, Sue-Min, Chan, Paul S, Bach, Richard G, Wang, Tracy Y, Spertus, John A, and Kosiborod, Mikhail. Diagnostic blood loss from phlebotomy and hospital- acquired anemia during acute myocardial infarction. Archives of internal medicine, 171(18):1646–1653, 2011.CrossRefGoogle ScholarPubMed
Thakkar, Rajiv N, Kim, Daniel, Knight, Amy M, Riedel, Stefan, Vaidya, Dhananjay, and Wright, Scott M. Impact of an educational intervention on the frequency of daily blood test orders for hospitalized patients. American journal of clinical pathology, 143(3):393–397, 2015.CrossRefGoogle ScholarPubMed
Hamilton, Richard John and Sewell, Peter Alexis. Introduction to high performance liquid chromatography, 1982.CrossRefGoogle Scholar
Kirkland, J J and McCormick, R M. Liquid phase separation methods: HPLC, FFF, electrophoresis. Chromatographia, 24(1):58–76, 1987.CrossRefGoogle Scholar
Shackelford, Carl L and Rainin, Kenneth. Modular liquid chromatography column apparatus, 1987.Google Scholar
Maldener, Gerhard. Requirements and tests for HPLC apparatus and methods in pharmaceutical quality control. Chromatographia, 28(1-2):85–88, 1989.CrossRefGoogle Scholar
Andersson, Rolf and Bruno, Hedlund. HPLC analysis of organic acids in lactic acid fermented vegetables. Zeitschrift f{ü}r Lebensmittel-Untersuchung und Forschung, 176(6):440–443, 1983.CrossRefGoogle ScholarPubMed
Hamann, J A, Johnson, K, and Jeter, Delbert T. HPLC determination of clenbuterol in pharmaceutical gel formulations. Journal of chromatographic science, 23(1):34– 36, 1985.CrossRefGoogle ScholarPubMed
Homma, Masato, Jayewardene, Anura L, Gambertoglio, John, and Aweeka, Francesca. High-performance liquid chromatographic determination of ribavirin in whole blood to assess disposition in erythrocytes. Antimicrobial agents and chemotherapy, 43(11):2716–2719, 1999.CrossRefGoogle ScholarPubMed
Kidd, Brian A, Hoffman, Gabriel, Zimmerman, Noah, Li, Li, Morgan, Joseph W, Glowe, Patricia K, Botwin, Gregory J, Parekh, Samir, Babic, Nikolina, Doust, Matthew W, et al. Evaluation of direct-to-consumer low-volume lab tests in healthy adults. The Journal of clinical investigation, 126(5):1734–1744, 2016.CrossRefGoogle ScholarPubMed
Zheng, Chunyang Y, Ma, Guanghui, and Su, Zhiguo. Native PAGE eliminates the problem of PEG-SDS interaction in SDS-PAGE and provides an alternative to HPLC in characterization of protein PEGylation. Electrophoresis, 28(16):2801– 2807, 2007.CrossRefGoogle ScholarPubMed
Diamandis, Eleftherios P. Theranos phenomenon: promises and fallacies. Clinical Chemistry and Laboratory Medicine (CCLM), 53(7):989–993, 2015.CrossRefGoogle ScholarPubMed
Blood Pressure Lowering Treatment Trialists’ Collaboration et al. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomized trials. The Lancet, 362(9395):1527–1535, 2003.CrossRefGoogle Scholar
Klonoff, David C, Lee Parkes, Joan, Kovatchev, Boris P, Kerr, David, Bevier, Wendy C, Brazg, Ronald L, Christiansen, Mark, Bailey, Timothy S, Nichols, James H, and Kohn, Michael A. Investigation of the accuracy of 18 marketed blood glucose monitors. Diabetes Care, 41(8):1681–1688, 2018.CrossRefGoogle ScholarPubMed
Pershad, Yash, Mascareno, Ashley A, Watson, Makoyi R, Brimhall, Alex L, Herbots, Nicole, Watson, Clarizza F, Krishnan, Abijith, Kannan, Nithin, Mangus, Mark W, Culbertson, Robert J, et al. Electrolyte Detection by Ion Beam Analysis, in Continuous Glucose Sensors and in Microliters of Blood using a Homogeneous Thin Solid Film of Blood, HemaDropTM. MRS Advances, 1(29):2133–2139, 2016.CrossRefGoogle Scholar
Pershad, Yash, Herbots, Nicole, Day, Grady, Van Haren, Ryan, Whaley, Shawn, Martinez, Alvaro, Suhartono, Sabrina, Culbertson, Robert, Mangus, Mark, and Wilkens, Barry. Determining Canine Blood and Human Blood Composition by Congealing Microliter Drops into Homogeneous Thin Solid Films (HTSFs) via HemaDropTM. MRS Advances, 2(45):2451–2456, 2017.CrossRefGoogle Scholar
Grüner, Nico, Stambouli, Oumaima, and Ross, R Stefan. Dried blood spots-preparing and processing for use in immunoassays and in molecular techniques. JoVE (Journal of Visualized Experiments), (97): e52619, 2015.Google ScholarPubMed
Mukhopadhyay, Sharmila M. Sample preparation for microscopic and spectroscopic characterization of solid surfaces and films. CHEMICAL ANALYSIS-NEW YORK- INTERSCIENCE THEN JOHN WILEY-, pages 377–412, 2003.Google Scholar
Greer, John P, DAA, Bertil Glader, List, Alan F, Means, Robert T, Paraskevas, Frixos, and Rodgers, George M. Wintrobe’s Clinical Hematology, (2014). Lippincott Williams & Wilkins, Philadelphia, 14 edition, 2014.Google Scholar
Fan, Rong, Vermesh, Ophir, Srivastava, Alok, Yen, Brian KH, Qin, Lidong, Ahmad, Habib, Kwong, Gabriel A, Liu, Chao-Chao, Gould, Juliane, Leroy, Hood, et al. Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nature biotechnology, 26(12):1373, 2008.CrossRefGoogle Scholar
Xing, Q., Hart, M. A., Culbertson, R., Bradley, J. D., Herbots, N., Wilkens, B. J., Watson, C. F. (2011). Particle-Induced X-ray Emission (PIXE) of silicate coatings on high impact resistance polycarbonates. In AIP Conference Proceedings (Vol. 1336, pp. 303-309) https://doi.org/10.1063/1.3586109 Qian Xing. Modeling Mechanisms of Water Affinity and Condensation on Si-based Surfaces via Experiments and Applications, Ph D thesis, Arizona State University (2011).Google Scholar
Herbots, Nicole, Suresh, N. C., Narayan., S.R., Day, J. M.., Thinakaran, H. L., Ram, S. , and Pershad, Y., 2019. Patent Pending.Google Scholar
Herbots, Nicole, Shaw, Justin M, Hurst, Q B, Grams, M P, Culbertson, R J, Smith, David J, Atluri, V, Zimmerman, P, and Queeney, K T. The formation of ordered, ultrathin SiO2/Si (1 0 0) interfaces grown on (1*1) Si (1 0 0). Materials Science and Engineering: B, 87(3):303–316, 2001.CrossRefGoogle Scholar
Dar, Khavar, Williams, Tim, Aitken, Richard, Woods, Kent L, and Fletcher, Susan. Arterial versus capillary sampling for analysing blood gas pressures. Bmj, 310(6971):24–25, 1995.CrossRefGoogle Scholar
Luukkonen, Antti AM, Lehto, Tiina M, Hedberg, Pirjo SM, and Vaskivuo, Tommy E. Evaluation of a hand-held blood gas analyzer for rapid determination of blood gases, electrolytes and metabolites in intensive care setting. Clinical Chemistry and Laboratory Medicine (CCLM), 54(4):585–594, 2016.CrossRefGoogle ScholarPubMed
Hatakeyama, Hiroto, Wu, Sherry Y, Mangala, Lingegowda S, Lopez- Berestein, Gabriel, and Sood, Anil K. Assessment of in vivo siRNA delivery in cancer mouse models, 2016.CrossRefGoogle Scholar
Mayer, M. SIMNRA user’s guide, report IPP 9/113. Max-Planck-Institut fur Plasmaphysik, Garching, Germany, 1(9):9, 1997.Google Scholar
Mayer, M. SIMNRA, a simulation program for the analysis of NRA, RBS and ERDA. In AIP Conference Proceedings, volume 475, pages 541–544, 1999.CrossRefGoogle Scholar
Eckstein, W and Mayer, M. Rutherford backscattering from layered structures beyond the single scattering model. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 153(1-4):337– 344, 1999.CrossRefGoogle Scholar
Mayer, M. Ion beam analysis of rough thin films. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 194(2):177–186, 2002CrossRefGoogle Scholar
Mayer, M, Arstila, Kai, Nordlund, Kai, Edelmann, Erik, and Keinonen, Juhani. Multiple scattering of MeV ions: Comparison between the analytical theory and Monte-Carlo and molecular dynamics simulations. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 249(1-2):823–827, 2006.CrossRefGoogle Scholar
Sabbatini, Luigia and Zambonin, Pier G. XPS and SIMS surface chemical analysis of some important classes of polymeric biomaterials. Journal of electron spectroscopy and related phenomena, 81(3):285–301, 1996.CrossRefGoogle Scholar
Boro, Ronald T and Cipolla, Sam J. Proton-excited X-ray analysis on whole blood using a small accelerator. Nuclear Instruments and Methods, 131(2):343–352.CrossRefGoogle Scholar
Chu, Wei-Ku, Mayer, James W., and Nicolet, Marc-A. Backscattering Spectrometry, Academic Press Inc., San Diego, California, 197Google Scholar