A biophysical marker of severity in sickle cell disease
The search for predictive indicators of disease has largely focused on molecular markers. However, biophysical markers, which can integrate multiple pathways, may provide a more global picture of pathophysiology. Sickle cell disease affects millions of people worldwide and has been studied intensely...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for the Advancement of Science (AAAS)
2014
|
| Online Access: | http://hdl.handle.net/1721.1/86116 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826195915624415232 |
|---|---|
| author | Mahadevan, L. Wood, David K. Soriano, Alicia HIggins, John M. Bhatia, Sangeeta N |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Mahadevan, L. Wood, David K. Soriano, Alicia HIggins, John M. Bhatia, Sangeeta N |
| author_sort | Mahadevan, L. |
| collection | MIT |
| description | The search for predictive indicators of disease has largely focused on molecular markers. However, biophysical markers, which can integrate multiple pathways, may provide a more global picture of pathophysiology. Sickle cell disease affects millions of people worldwide and has been studied intensely at the molecular, cellular, tissue, and organismal level for a century, but there are still few, if any, markers quantifying the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as an indicator of disease severity. Here, we use a microfluidic device to characterize the dynamics of “jamming,” or vaso-occlusion, in physiologically relevant conditions, by measuring a biophysical parameter that quantifies the rate of change of the resistance to flow after a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish patients with poor outcomes from those with good outcomes, unlike existing laboratory tests. This biophysical indicator could therefore be used to guide the timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drugs, transfusion, and novel small molecules in an ex vivo setting. |
| first_indexed | 2024-09-23T10:17:51Z |
| format | Article |
| id | mit-1721.1/86116 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:17:51Z |
| publishDate | 2014 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/861162022-09-30T20:09:57Z A biophysical marker of severity in sickle cell disease A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease Mahadevan, L. Wood, David K. Soriano, Alicia HIggins, John M. Bhatia, Sangeeta N Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Koch Institute for Integrative Cancer Research at MIT Wood, David K. Bhatia, Sangeeta N. The search for predictive indicators of disease has largely focused on molecular markers. However, biophysical markers, which can integrate multiple pathways, may provide a more global picture of pathophysiology. Sickle cell disease affects millions of people worldwide and has been studied intensely at the molecular, cellular, tissue, and organismal level for a century, but there are still few, if any, markers quantifying the severity of this disease. Because the complications of sickle cell disease are largely due to vaso-occlusive events, we hypothesized that a physical metric characterizing the vaso-occlusive process could serve as an indicator of disease severity. Here, we use a microfluidic device to characterize the dynamics of “jamming,” or vaso-occlusion, in physiologically relevant conditions, by measuring a biophysical parameter that quantifies the rate of change of the resistance to flow after a sudden deoxygenation event. Our studies show that this single biophysical parameter could be used to distinguish patients with poor outcomes from those with good outcomes, unlike existing laboratory tests. This biophysical indicator could therefore be used to guide the timing of clinical interventions, to monitor the progression of the disease, and to measure the efficacy of drugs, transfusion, and novel small molecules in an ex vivo setting. National Institute for Biomedical Imaging and Bioengineering (U.S.) (National Research Service Award Fellowship) 2014-04-11T17:20:35Z 2014-04-11T17:20:35Z 2012-02 2011-06 Article http://purl.org/eprint/type/JournalArticle 1946-6234 1946-6242 http://hdl.handle.net/1721.1/86116 Wood, D. K., A. Soriano, L. Mahadevan, J. M. Higgins, and S. N. Bhatia. “A Biophysical Indicator of Vaso-Occlusive Risk in Sickle Cell Disease.” Science Translational Medicine 4, no. 123 (February 29, 2012): 123ra26–123ra26. https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1126/scitranslmed.3002738 Science Translational Medicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Mahadevan, L. Wood, David K. Soriano, Alicia HIggins, John M. Bhatia, Sangeeta N A biophysical marker of severity in sickle cell disease |
| title | A biophysical marker of severity in sickle cell disease |
| title_full | A biophysical marker of severity in sickle cell disease |
| title_fullStr | A biophysical marker of severity in sickle cell disease |
| title_full_unstemmed | A biophysical marker of severity in sickle cell disease |
| title_short | A biophysical marker of severity in sickle cell disease |
| title_sort | biophysical marker of severity in sickle cell disease |
| url | http://hdl.handle.net/1721.1/86116 https://orcid.org/0000-0002-1293-2097 |
| work_keys_str_mv | AT mahadevanl abiophysicalmarkerofseverityinsicklecelldisease AT wooddavidk abiophysicalmarkerofseverityinsicklecelldisease AT sorianoalicia abiophysicalmarkerofseverityinsicklecelldisease AT higginsjohnm abiophysicalmarkerofseverityinsicklecelldisease AT bhatiasangeetan abiophysicalmarkerofseverityinsicklecelldisease AT mahadevanl abiophysicalindicatorofvasoocclusiveriskinsicklecelldisease AT wooddavidk abiophysicalindicatorofvasoocclusiveriskinsicklecelldisease AT sorianoalicia abiophysicalindicatorofvasoocclusiveriskinsicklecelldisease AT higginsjohnm abiophysicalindicatorofvasoocclusiveriskinsicklecelldisease AT bhatiasangeetan abiophysicalindicatorofvasoocclusiveriskinsicklecelldisease AT mahadevanl biophysicalmarkerofseverityinsicklecelldisease AT wooddavidk biophysicalmarkerofseverityinsicklecelldisease AT sorianoalicia biophysicalmarkerofseverityinsicklecelldisease AT higginsjohnm biophysicalmarkerofseverityinsicklecelldisease AT bhatiasangeetan biophysicalmarkerofseverityinsicklecelldisease |