Healthcare workers (HCWs) are the first responders when infectious pathogens occur. Powered air-purifying respirators (PAPRs) are one of the most widely used personal protective equipment for healthcare workers. Currently, few studies have been performed with HCWs in the actual healthcare work environments to assess discomforts, acceptance and protective efficiency towards wearing and use of PAPRs. The main purpose of this dissertation was to introduce and assess a brand new unconventional PAPR (Koken breath-response PAPR). The protection performance and user preferance of this unconventional PAPR were studided and compared to that of a N95 FFR and traditional PAPRs. Firstly, a laboratory experiment was conducted to test the performance of the unconventional breath-response respirator (Koken PAPR) during different breathing flow types and rates, faceseal leakages, and motor conditions (fan on or fan off). The results First and foremost, I would like to express my sincere gratitude to my advisor Dr. Xinjian (Kevin) He. Without his support, I would not have the opportunity to pursue my Ph.D. degree in West Virginia University. My sincerely thanks not only for his tremendous and continuous academic support, but also for his patience, motivation, and immense knowledge. His guidance helped me in all the time of research and writing of this dissertation. Dr. He is the greatest advisor that I have ever met in my Ph.D. study. I also would like to thank Dr. Anna Allen for providing professional guidance on my dissertation research. This work would not have been possiblely completed without her endless help.