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Extraction and biomolecular analysis of dermal interstitial fluid collected with hollow microneedles

Journal Article · · Communications Biology
 [1];  [2];  [3];  [3];  [4];  [5];  [6];  [6];  [6];  [6];  [6];  [2];  [5]
  1. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); DOE/OSTI
  2. Univ. of New Mexico, Albuquerque, NM (United States)
  3. Excet Inc., Springfield, VA (United States)
  4. US Army Edgewood Chemical Biological Center, Edgewood, MD (United States)
  5. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
  6. Sandia National Lab. (SNL-CA), Livermore, CA (United States)

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize. Here, we present a facile microneedle approach for dermal ISF extraction with minimal pain and no blistering for human subjects and rats. Extracted ISF volumes were sufficient for determining transcriptome, and proteome signatures. We noted similar profiles in ISF, serum, and plasma samples, suggesting that ISF can be a proxy for direct blood sampling. Dynamic changes in RNA-seq were recorded in ISF from induced hypoxia conditions. Finally, we report the first isolation and characterization, to our knowledge, of exosomes from dermal ISF. The ISF exosome concentration is 12–13 times more enriched when compared to plasma and serum and represents a previously unexplored biofluid for exosome isolation. This minimally invasive extraction approach can enable mechanistic studies of ISF and demonstrates the potential of ISF for real-time health monitoring applications.

Research Organization:
Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); Defense Threat Reduction Agency (DTRA); Edgewood Chemical Biological Center (ECBC); National Institutes of Health (NIH)
Grant/Contract Number:
NA0003525
OSTI ID:
1624529
Alternate ID(s):
OSTI ID: 1871985
Journal Information:
Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 1; ISSN 2399-3642
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

References (59)

Influence of Array Interspacing on the Force Required for Successful Microneedle Skin Penetration: Theoretical and Practical Approaches journal April 2013
Suction blister fluid as potential body fluid for biomarker proteins journal September 2007
Exosomes in bodily fluids are a highly stable resource of disease biomarkers journal March 2015
Drilling accurate nanopores for biosensors by energetic multi-wall carbon nanotubes: a molecular dynamics investigation journal September 2022
Minimally-invasive transepidermal potentiometry with microneedle salt bridge journal June 2016
Advances in the Prevention and Treatment of High Altitude Illness journal May 2017
Microneedle array for transdermal biological fluid extraction and in situ analysis journal September 2004
Non-invasive evaluation of skin cytokines secretion: An innovative complementary method for monitoring skin disorders journal May 2013
Orthogonality of Separation in Two-Dimensional Liquid Chromatography journal October 2005
Suction Blister Device for Separation of Viable Epidermis from Dermis* journal February 1968
Semi-supervised learning for peptide identification from shotgun proteomics datasets journal October 2007
Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2 journal June 2020
A hemimetabolous wing development suggests the wing origin from lateral tergum of a wingless ancestor journal February 2022
Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens journal March 2021
Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress journal September 2022
Precise Microinjection into Skin Using Hollow Microneedles journal May 2006
Minimally Invasive Extraction of Dermal Interstitial Fluid for Glucose Monitoring Using Microneedles journal February 2005
Measurement of skin surface biomakers by Transdermal Analyses Patch following different in vivo models of irritation: a pilot study journal November 2016
Pen needle design influences ease of insertion, pain, and skin trauma in subjects with type 2 diabetes journal December 2016
Suction effusion fluid from skin and constituent analysis: new candidate for interstitial fluid journal November 1992
Analysis of ultrasonically extracted interstitial fluid as a predictor of blood glucose levels journal September 2000
Acute high-altitude sickness journal January 2017
1D and 2D annotation enrichment: a statistical method integrating quantitative proteomics with complementary high-throughput data journal November 2012
Development of TAP, a non-invasive test for qualitative and quantitative measurements of biomarkers from the skin surface journal January 2014
Isolation of Exosomes from Blood Plasma: Qualitative and Quantitative Comparison of Ultracentrifugation and Size Exclusion Chromatography Methods journal December 2015
Isolation, identification, and characterization of novel nanovesicles journal May 2016
populacDNA normalization by hydroxyapatite chromatography to enrich transcriptome diversity in RNA-seq applications journal December 2012
Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene journal July 2006
Peregrine: A rapid and unbiased method to produce strand-specific RNA-Seq libraries from small quantities of starting material journal April 2013
Evaluating the Molecular Basis for Acute Mountain Sickness: Hypoxia Response Gene Expression Patterns in Warfighters and Murine Populations journal November 2013
Suction blister fluid as a model for interstitial fluid in rats journal January 1978
Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring journal May 2016
Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution journal November 2010
Fast gapped-read alignment with Bowtie 2 journal March 2012
NIH Image to ImageJ: 25 years of image analysis journal June 2012
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist journal January 2020
Optimal Statistical Incorporation of Independent Feature Stability Information into Radiomics Studies journal January 2020
Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter journal January 2021
Microneedle-based sensors for medical diagnosis journal January 2016
Microdialysis methodology for the measurement of dermal interstitial fluid in humans journal June 1996
Multiplexed, Quantitative Workflow for Sensitive Biomarker Discovery in Plasma Yields Novel Candidates for Early Myocardial Injury journal February 2015
HTSeq--a Python framework to work with high-throughput sequencing data journal September 2014
Adjusting batch effects in microarray expression data using empirical Bayes methods journal April 2006
Analytical Characterization of Electrochemical Biosensor Test Strips for Measurement of Glucose in Low-Volume Interstitial Fluid Samples journal September 1999
2016 update of the PRIDE database and its related tools journal November 2015
2016 update of the PRIDE database and its related tools journal September 2016
Microdialysis methodology for the measurement of dermal interstitial fluid in humans journal June 1996
Suction blister device for separation of viable epidermis from dermis journal January 2004
Mechanisms of intermittent hypoxia induced hypertension journal October 2009
Silicon microneedle array for minimally invasive human health monitoring conference March 2018
Intermittent hypoxia in rats reduces activation of Ca 2+ sparks in mesenteric arteries journal December 2015
Differential effects of chronic hypoxia and intermittent hypocapnic and eucapnic hypoxia on pulmonary vasoreactivity journal January 2008
Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20 and VEGF production by human monocytes and macrophages journal September 2013
Quantifying the Composition of Human Skin for Glucose Sensor Development journal September 2010
1D and 2D annotation enrichment: a statistical method integrating quantitative proteomics with complementary high-throughput data journal November 2012
DAVID: Database for Annotation, Visualization, and Integrated Discovery journal January 2003
Targeting Tumor Adaption to Chronic Hypoxia: Implications for Drug Resistance, and How It Can Be Overcome journal August 2017
Standardization of sample collection, isolation and analysis methods in extracellular vesicle research journal January 2013
Evaluating the Molecular Basis for Acute Mountain Sickness: Hypoxia Response Gene Expression Patterns in Warfighters and Murine Populations journal November 2013

Cited By (7)

Lipid profiling of suction blister fluid: comparison of lipids in interstitial fluid and plasma journal August 2019
A Hydrogel Microneedle Patch for Point‐of‐Care Testing Based on Skin Interstitial Fluid journal January 2020
Advances in the Formulations of Microneedles for Manifold Biomedical Applications journal April 2020
Parametric study of 3D printed microneedle (MN) holders for interstitial fluid (ISF) extraction journal February 2020
Accessing analytes in biofluids for peripheral biochemical monitoring journal February 2019
Serum-borne factors alter cerebrovascular endothelial microRNA expression following particulate matter exposure near an abandoned uranium mine on the Navajo Nation journal July 2020
Engineering Microneedles for Therapy and Diagnosis: A Survey journal March 2020

Figures / Tables (10)