1 Research 2 Real-time metabolic heat-based specific growth rate soft sensor for monitoring and control 3 of high molecular weight HA production by Streptococcus zooepidemicus. 4 Naresh Mohan1,#, Satya Sai Pavan1,# Anjali Jayakumar1, Sivakumar Rathinavelu1, Senthilkumar 5 Sivaprakasam*,1 6 7 Authors’ official mail 8 Naresh Mohan –
[email protected] 9 Satya Sai Pavan –
[email protected] 10 Anjali Jayakumar –
[email protected] 11 Sivakumar Rathinavelu –
[email protected] 12 Senthilkumar Sivaprakasam –
[email protected] 13 1BioPAT Laboratory, Department of Biosciences & Bioengineering, Indian Institute of 14 Technology Guwahati, Guwahati-781039, Assam, India. 15 # Equally contributed. 16 *Correspondence: 17 Dr. Senthilkumar Sivaprakasam, 18 Associate Professor, 19 Department of Biosciences and Bioengineering, 20 Indian Institute of Technology Guwahati, 21 Guwahati – 781039, Assam. 22 Tel: +91 361 2582226. 23 Fax: +91 361 2582249 1 24 Abstract 25 Background: Hyaluronic acid (HA) is an important mucopolysaccharide of higher molecular 26 weight range and holds sheer economic interest. Its applications are widely acknowledged in 27 rheumatoid arthritis treatment, tissue engineering, and cosmetics industries. This present 28 investigation aims for the fed-batch production of high molecular weight range HA by 29 application of real-time metabolic heat measurements. 30 31 Results: Fed-batch strategies based on Feedforward (FF) and Feedback (FB) control was devised 32 to improve the Molecular Weight (MW) of HA production by S. zooepidemicus. Metabolic heat 33 measurements (Fermentation calorimetry) were modeled to decipher real-time specific growth 34 rate, was looped to the PID circuit, envisaged to control to their desired setpoint values 35 0.05 h , 0.1 h and 0.15 h respectively.