A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin.
Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson's r = 0.86; p < 0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 μg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community.
Junxin
J
Wang
Fang
F
Chen
Santiago J
SJ
Arconada-Alvarez
James
J
Hartanto
Molecular Imaging Center, University of Southern California Keck School of Medicine , Los Angeles, California 90089, United States.
Li-Peng
LP
Yap
Molecular Imaging Center, University of Southern California Keck School of Medicine , Los Angeles, California 90089, United States.
Ryan
R
Park
University of Science and Technology Beijing, Research Center for Bioengineering and Sensing Technology , Beijing 100083, People's Republic of China.
Fang
F
Wang
Molecular Imaging Center, University of Southern California Keck School of Medicine , Los Angeles, California 90089, United States.
Ivetta
I
Vorobyova
Molecular Imaging Center, University of Southern California Keck School of Medicine , Los Angeles, California 90089, United States.
Grant
G
Dagliyan
Molecular Imaging Center, University of Southern California Keck School of Medicine , Los Angeles, California 90089, United States.
Peter S
PS
Conti
Jesse V
JV
Jokerst
Anticoagulation therapy; heparin; optoacoustics; partial thromboplastin time; photoacoustic imaging; silica nanoparticles; therapeutic drug monitoring
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