This research will develop wearable sensors analogous to the pulse oximeter, but to monitor heparin anticoagulation therapy and other drugs with a narrow therapeutic window. This work is exceptionally innovative and completely distinct from other work on therapeutic drug monitoring because it is sample-free, acoustics-based, non-invasive, and real-time. This approach is also the only design to measure the heparin/anti-thrombin complex in contrast to existing surrogate methods that simply measure clotting time. Although applicable to multiple drugs, we will focus on heparin because it is a cornerstone (500M doses/year) of surgical and cardiovascular medicine. Heparin has variable molecular weight, activity, biodistribution, and pharmacokinetics resulting in a narrow therapeutic window causing heparin to be the second most common medication error. The current standard for heparin monitoring is the activated partial thromboplastin time (aPTT); however, this in vitro diagnostic tool suffers from long turnaround times, a variable reference range, and poor correlation to outcome. To solve this, I will develop novel wearable ultrasound-based sensors. In particular, I will use photoacoustic imaging?a hybrid approach that uses incident light pulses to trigger an acoustic signal. Its spectral nature, intense contrast, and high frame rate facilitates real-time, multiplexed, and high sensitivity measurements. These are ideal features for therapeutic drug monitoring. First, we will synthesize novel sensing molecules. We will then integrate these chemical sensors into wearable devices that will interact with ultrasound transducers to quantitate coagulation without venipuncture. In the final phases of the program, we will validate this approach with animal models and expand this to other drugs such as digoxin and phenytoin as well as multiplexed sensors. Rather than injecting a contrast agent and hoping it goes to the site of disease in vivo or drawing blood and processing it in vitro, this work will immobilize a sensor in situ for constant feedback on anticoagulation therapy. The confluence of imaging technology, wearable technology, and chemical technology that I offer here will truly revolutionize the incredibly common practice of heparin therapy?patients will no longer be subjected to invasive sampling and will avoid dangerous overdoses and underdoses. Doctors and nurses will have instantaneous feedback on their patients and smart infusion pumps will carefully and automatically titrate drug dosages. Long term, this work will translate into significant cost savings for insurers and providers.

Public Health Relevance

Heparin is an anticoagulant or blood thinner given to people in intensive care, undergoing surgery, and with clotting disorders, but it has a narrow concentration window in which it is both safe and effective. Many patients are harmed when too much or too little heparin is given, and thus I will develop a real-time and wearable sensor to monitor blood coagulation. This tool will replace blood draws and result in a safer and more effective medicine.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2HL137187-01
Application #
9165380
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56)R)
Program Officer
Danthi, Narasimhan
Project Start
2016-09-30
Project End
2021-06-30
Budget Start
2016-09-30
Budget End
2021-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$2,325,000
Indirect Cost
$825,000
Name
University of California San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Chen, Fang; Hableel, Ghanim; Zhao, Eric Ruike et al. (2018) Multifunctional nanomedicine with silica: Role of silica in nanoparticles for theranostic, imaging, and drug monitoring. J Colloid Interface Sci 521:261-279
Kim, Taeho; Zhang, Qiangzhe; Li, Jin et al. (2018) A Gold/Silver Hybrid Nanoparticle for Treatment and Photoacoustic Imaging of Bacterial Infection. ACS Nano :
Kang, Jinyoung; Kim, Dokyoung; Wang, Junxin et al. (2018) Enhanced Performance of a Molecular Photoacoustic Imaging Agent by Encapsulation in Mesoporous Silicon Nanoparticles. Adv Mater 30:e1800512
Moore, Colman; Bai, Yuting; Hariri, Ali et al. (2018) Photoacoustic imaging for monitoring periodontal health: A first human study. Photoacoustics 12:67-74
Hariri, Ali; Wang, Junxin; Kim, Yeji et al. (2018) In vivo photoacoustic imaging of chorioretinal oxygen gradients. J Biomed Opt 23:1-8
Chen, Fang; Li, Gongyi; Zhao, Eric Ruike et al. (2018) Cellular toxicity of silicon carbide nanomaterials as a function of morphology. Biomaterials 179:60-70
Dhong, Charles; Edmunds, Samuel J; Ramírez, Julian et al. (2018) Optics-Free, Non-Contact Measurements of Fluids, Bubbles, and Particles in Microchannels Using Metallic Nano-Islands on Graphene. Nano Lett 18:5306-5311
Pohling, Christoph; Campbell, Jos L; Larson, Timothy A et al. (2018) Smart-Dust-Nanorice for Enhancement of Endogenous Raman Signal, Contrast in Photoacoustic Imaging, and T2-Shortening in Magnetic Resonance Imaging. Small 14:e1703683
Lin, C Y; Chen, F; Hariri, A et al. (2018) Photoacoustic Imaging for Noninvasive Periodontal Probing Depth Measurements. J Dent Res 97:23-30
Wang, Junxin; Lin, Ching-Yu; Moore, Colman et al. (2018) Switchable Photoacoustic Intensity of Methylene Blue via Sodium Dodecyl Sulfate Micellization. Langmuir 34:359-365

Showing the most recent 10 out of 17 publications