2 results
Optimizing Homogeneous Thin Solid Films (HTSFs) from µL-Blood Droplets via Hyper-Hydrophilic Coatings (HemaDropTM) for Accurate Compositional Analysis via IBA, XRF, and XPS
- Nicole Herbots, Nikhil C. Suresh, Shaurya Khanna, Saaketh R. Narayan, Amber A. Chow, Mohammed Sahal, Sukesh Ram, Jack M. Day, Yash W. Pershad, Harshini L. Thinakaran, Robert J. Culbertson, Eric J. Culbertson, Karen L. Kavanagh
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- Journal:
- MRS Advances / Volume 4 / Issue 46-47 / 2019
- Published online by Cambridge University Press:
- 23 October 2019, pp. 2489-2513
- Print publication:
- 2019
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- Article
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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.
Electrolyte Detection by Ion Beam Analysis, in Continuous Glucose Sensors and in Microliters of Blood using a Homogeneous Thin Solid Film of Blood, HemaDrop™
- Yash Pershad, Ashley A. Mascareno, Makoyi R. Watson, Alex L. Brimhall, Nicole Herbots, Clarizza F. Watson, Abijith Krishnan, Nithin Kannan, Mark W. Mangus, Robert J. Culbertson, B. J. Wilkens, E. J. Culbertson, T. Cappello-Lee, R.A. Neglia
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- Journal:
- MRS Advances / Volume 1 / Issue 29 / 2016
- Published online by Cambridge University Press:
- 21 June 2016, pp. 2133-2139
- Print publication:
- 2016
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Percolation of blood and of interstitial fluids into implantable continuous glucose sensors (CGS) for diabetics presently limits sensor lifetime between 3 and 7 days. Na+ mobile ions in body fluids damage Si-based CGS sensors electronics. The direct detection of Na percolation is investigated by Ion Beam Analysis (IBA) and Proton Induced X-ray Emission (PIXE) in previously used CGS. Based on these results, a new technology called HemaDropTM is then tested to prepare small volume (5-10 µL) of blood for IBA. A species’s detectability by IBA scales with the square of the ratio of element’s atomic number Z to that of the substrate. Because Na has a low atomic number (Z=11), Si signals from sensor substrates can prevent Na detection in Si by 2 mega electron volt (MeV) IBA.
Using 4.7 MeV 23Na (α, α)23Na nuclear resonance (NR) can increase the 23Na scattering cross section and thus its detectability in Si. The NR energy, width, and resonance factor, is calibrated via two well-known alpha (α) particle signals with narrow energy spreads: a 5.486 ± 0.007 MeV 241Am α-source (ΔΕ = 0.12%) and the 3.038 ± 0.003 MeV 16O(α, α)16O NR (ΔΕ = 0.1%). Next, the NR cross section is calibrated via 100 nm NaF thin films on Si(100) by scanning the beam energy. The23Na (α, α) NR energy is found to be 4.696 ± 0.180 MeV, and the NR/RBS cross section 141 ± 7%. This is statistically significant but small compared to the 4.265 MeV 12C NR (1700%) and 3.038 MeV 16O NR (210%), and insufficient to detect small amounts of 23Na in Si. Next, a new method of sample preparation HemaDropTM, is tested for detection of elements in blood, such Fe, Ca, Na, Cl, S, K, C, N, and O, as an alternative to track fluid percolation and Na diffusion in damaged sensors. Detecting more abundant, heavier elements in blood and interstitial fluids can better track fluid percolation and Na+ ions in sensors. Both Na detection and accuracy of measured blood composition by IBA is greatly improved by using HemaDropTM sample preparation to create Homogeneous Thin Solid Films (HTSFs) of blood from 5-10 µL on most substrates. HTSF can be used in vacuo such as 10-8 –10-6 Torr).