Narrowing the Gap to Characterize Sickle Cell Disease

Microfluidic Future is by no means an accurate representation of all the current, ongoing research in microfluidics. Nevertheless, the fact that you won’t be able to find any articles about assays relying on a biophysical marker isn’t too far off the reality in microfluidics. I suppose this is partly due to the incredible amount of previous work on molecular markers when high resolution control hadn’t been realized yet. Regardless, I was happy to come across an article about a microfluidic device that indicates sickle cell disease risk using the disease’s biophysical characteristics. The work “A Biophysical Indicator of Vaso-occusive Risk in Sickle Cell Disease” appeared in Science Translational Medicine this past February and is a result of ongoing sickle research by MIT and Harvard Medical School. My friend originally forwarded me an article about it on Medgadget, which you should also check out, along with the podcast it mentions.

Sickle Cell Disease

Red blood cells with abnormal Hemoglobin (HbS) can form into a sickle shape and occlude blood vessels (image source)

Red blood cells with abnormal Hemoglobin (HbS) can form into a sickle shape and occlude blood vessels (image source)

Sickle cell disease affects more than 13 million people worldwide and is responsible for $1.1 billion in costs per year in the United States. A mutation in the hemoglobin molecule causes red blood cells to change shape and stiffen when releasing oxygen. This shape change in many red blood cells can occlude a blood vessel, resulting in a crisis. While this fundamental component of the disease is known, there are many factors and processes relating to this event that are still unknown, resulting in an inability to discern the severity of sickle cell disease for a particular patient, besides the fact that they have it. The ability to predict the severity of the sickle cell disease would both aid the development of new therapies and guide clinical intervention.

Characterizing Disease Severity

The authors of this paper have previously demonstrated that they could simulate the vaso-occlusive crisis events by altering the oxygen concentration of sickle cell disease blood flowing through a capillary-sized microchannel. This paper takes it a step further and quantifies how the blood conductance, defined as velocity per unit pressure drop, changes during the events and uses it as a measure of disease severity. When the authors reduced the oxygen content, blood velocity would decrease, despite the constant pressure applied. The authors hypothesized that the conductance would change faster for patients with severe sickle cell disease as opposed to patients with a more benign form of the disease. You can see that the conductance of a patient with benign sickle cell disease (A) and that of a patient with severe sickle cell disease (B) are drastically different.

Blood from a patient with benign sickle cell disease (A) and sever sickle cell disease (B) were both subjected to changes in oxygen concentration, indicated by the top panels. This resulted in drastically different changes in conductance, which could distinguish the two types of patients.

Blood from a patient with benign sickle cell disease (A) and sever sickle cell disease (B) were both subjected to changes in oxygen concentration, indicated by the top panels. This resulted in drastically different changes in conductance, which could distinguish the two types of patients.

Device Value

As I mentioned, this device has potential use in developing therapies for sickle cell disease. The authors demonstrated this with 5-hydroxymethyl furfural (5HMF), which is known to increase hemoglobin oxygen affinity. Hemoglobin with a higher oxygen affinity would retain its ‘safe’ structure as it would release its oxygen less readily. As expected, this molecule caused a fivefold slower reduction in conductance change compared to an untreated, severe blood sample. While this device’s strength originates in its focus on biophysical markers, it could also be utilized to further understand the process of vaso-occlusive events and guide the handling of patients and discovery of effective therapies.

Regardless of the praise this paper has already received, I think it’s rather solid, and I’m not sure what else I would have liked to see addressed. Don’t expect to see this in your local pharmacy any time soon, though, since it can’t predict the occurrence of crises, but instead would indicate what treatment a patient would need.

Reference:

ResearchBlogging.org Wood DK, Soriano A, Mahadevan L, Higgins JM, & Bhatia SN (2012). A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease Science Translational Medicine, 4 (123), 1-8 PMID: 22378926