Microfluidic cellular synthesis of heparin

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Jonathan Dordick and his associates at RPI have succeeded in creating an artificial Golgi apparatus capable of mimicking the cellular organelle's ability to synthesize complex organic molecules and catalyze intricate reactions. In cells, the Golgi apparatus is responsible for numerous functions including the synthesis of polymers called glycosaminoglycans (using enzymes called glycosyltransferases found within the organelle). One of those glycosaminoglycan products, heparin, is a valuable pharmaceutical used to prevent coagulation of blood. To date, the only means of producing medical grade heparin require purification of harvested animal tissue or complex organic synthesis reaction. The artificial Golgi apparatus developed by Dr. Dordick and his team may some day be a viable alternative that does not require animal matter or toxic organic chemicals. In natural Golgi apparatuses, nascent compounds are shuttled between cisternae (stacked, membrane-bound sacks) and modified by the specific enzymes and compounds enclosed within each in an assembly line fashion. The artificial Golgi apparatus developed by Dr. Dordick and his team mimics this mechanism with a chip containing up to 100,000 microscopic gold squares. Each square contains different enzymes that have been immobilized in place. A computer is then able to physically move droplets of water between squares so that compounds dissolved in the solution can be modified in a systematic pattern. The movement is facilitated by electrically charging individual squares, which attracts the magnetic particles within the droplets. The order and timing of the movement can be modified so as to fine tune synthesis. In this way, the precise assembly line style production of chemicals like heparin in the Golgi apparatus is mimicked.

Key Differentiators

Raising cattle has an enormous carbon footprint; moreover, a great quantity of other waste is produced in the process. Laboratory synthesis techniques for producing heparin are costly, time intensive, toxic, and unsuitable for industrial-scale operation. The artificial Golgi apparatus involves reusable enzymes and predominately non-toxic chemicals. In addition, it holds the potential for cost-effective industrial up-scaling.

Challenges Solved

Until very recently, producing pharmaceutical grade heparin has exclusively involved harvesting organs from slaughtered cows and pigs and performing purification of the material. Newer techniques are capable of synthesizing the compound in a laboratory but are expensive and require toxic reagents and solvents. Biomimetic techniques for heparin synthesis like the lab-on-chip Golgi apparatus developed by Dr. Dordick at RPI may some day make production of heparin cheaper and less environmentally taxing.

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Journal article
Toward an Artificial Golgi: Redesigning the Biological Activities of Heparan Sulfate on a Digital Microfluidic ChipJournal of the American Chemical SocietyJuly 10, 2009
Martin JG; Gupta M; Xu Y; Akella S; Liu J; Dordick JS; Linhardt RJ

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