Bioanalysis Zone

New Investigator Award Finalist: Yu Shrike Zhang

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Yu Shrike_finalist_MPUFind out more about the other finalists

Comments from voters:

  • “His work is impressive, progressive and he not only is doing incredible work, but his career holds even greater promises in the future. He is a leader in non-animal research methods, the humane and better science of today and tomorrow.”
  • “He is one of the very few young and brilliant scientists I have come across in my scientific career. His enthusiasm for science is infectious.”
  • “I have read and followed Dr. Zhang’s research. His path breaking research ranging from organ-on-chip to biomaterial, deadly cancer to cardiac ailments, is extraordinary. As a budding scientist, I would like to see him flourish and bring innovation for solving unmet clinical needs.”

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What made you chose a career in bioanalysis?

A small improvement in bioanalysis could transform the way people conduct biomedical research. Since early times of my graduate training, I realized that imaging 3D tissue constructs was extremely challenging. I solved this problem by introducing photoacoustic microscopy to non-invasive, volumetric imaging of engineered tissues with deep penetration and high resolution. Through this experience I realized that developing appropriate bioanalytical tools holds key to tackle many bottlenecks in biomedicine. Therefore, I decided to devote my career to bioanalysis, not only due to its vital importance but also the passion and pride I derive from being a part of the community.

Describe the main highlights of your bioanalytical work?

In my graduate research, I pioneered the applications of photoacoustic microscopy in non-invasive, volumetric characterization of tissue-biomaterial interactions both in vitro and in vivo. During my postdoctoral training, I developed a series of novel on-chip biosensing platforms by integrating sophisticated microfluidic circuitry and valve/flow controllers to achieve, for the first time, fully automated, continual, and multiplexed monitoring of organoid behaviors for drug-screening applications. These biosensing platforms include miniature imagers for characterizing the morphological alterations of the organoids, physical sensors for monitoring microenvironmental parameters (e.g. pH, oxygen, temperature), and biochemical sensors for measuring organoid-secreted soluble biomarkers at trace concentrations. These microfluidic biosensors are critical in providing real-time information of the biological responses of the organoids towards pharmaceutical compounds over extended periods of time without human interference. I have also invented a transformative technology termed the expansion mini-microscopy (ExMM), which elegantly combines physical expansion of biological specimens with mini-microscopy for high-resolution imaging at extremely low cost. I am now carrying these advanced bioanalytical techniques into the research of my recent independence as a junior faculty with a shift in focus towards cancer precision therapy, by producing patient cancer models equipped with high-capacity biosensors for personalized chemotherapeutic drug screening.

How has your work impacted your laboratory, the bioanalytical field and beyond?

All stages of my bioanalytical research have widely impacted both my colleagues and the bioanalytical field. For example, the non-invasive, volumetric imaging technology based on photoacoustic microscopy has resulted in 7 publications in prestigious journals such as Angewandte Chemie, Biomaterials, and Tissue Engineering. My labmates had carried this strategy onwards in characterizing cell-biomaterial interactions. The innovation was further recognized by the community where subsequent review papers positively discussed its usefulness. The various microfluidic biosensing platforms that I developed during postdoctoral research extending into my independence, also generated a series of publications in journals such as Analytical Chemistry and Proceedings of the National Academy of Sciences USA. These innovations in multi-sensor-integrated organs-on-chips systems have been featured by numerous media such as British Broadcasting Corporation, Canadian Broadcasting Corporation, and Brigham and Women’s Hospital news. The unique microfluidic integration will likely transform the way pharmaceutical screening is conducted in the near future.

Describe the most difficult challenge you have encountered in your scientific career and how you overcame it?

The most difficult challenges throughout my career in bioanalysis happen to coincide with each other – that is, to establish an entirely new direction with limited prior experiences to learn from. At the early stage of my graduate research, I was not able to defend my hypothesis that uniform 3D scaffolds induce better cell distribution and angiogenesis than non-uniform counterparts, because cryo-sectioning often crushed the scaffolds instead of cutting them into thin pieces that could be observed under optical microscopy. Fortunately, I took an unusual way to solve this problem by switching to photoacoustic microscopy, necessitating no more sectioning. With these experiences, I felt comfortable to do it again in my postdoctoral training by building up a project from scratch and gearing it towards microfluidics-integrated biosensing, an exciting new direction for me and the laboratory then. After three years of efforts, I developed several multiplexed biosensing platforms capable of continual, non-invasive analysis of biophysical and biochemical parameters in organoid cultures. This most difficult challenge – setting up a research direction with minimal guidance – has well prepared me to transition into recent independence, where I am taking another new direction of applying these bioanalytical tools to cancer precision medicine.

Describe your role in bioanalytical communities/groups?

My contribution to the bioanalysis community has been recognized by several major awards such as the Baxter Young Investigator Award 2015, Lush Prize Young Researcher Americas 2016, and Society of Toxicology Biotech Specialty Section Outstanding Young Investigator Award 2017. I am a member of the Biomedical Engineering Society, Society of Photo-Optical Instrumentation Engineers, and American Association of Pharmaceutical Scientists focusing on optical, biophysical, and biochemical analyses of organ-on-chip systems. I have organized and chaired multiple sessions on biosensing topics in the annual Micro- and Nanotechnologies for Medicine Workshop. I have been invited to present my bioanalysis research at >20 university/institution seminars, conferences, and workshops. I have reviewed >50 bioanalysis-related manuscripts for many journals such as Advanced Materials, Small, Lab Chip, Toxicology in vitro, and RSC Advances. I recent took a position of Editor-in-Chief for the new journal Microphysiological Systems, where bioanalysis is a major part of the research the journal publishes. I am also devoted to educating next-generation scientists in bioanalysis. For example, Julio Aleman who co-authored the PNAS paper, is now pursuing graduate studies at Wake Forest Institute for Regenerative Medicine focusing on organ-on-chip platforms for drug screening. He recently won the prestigious MIT TR35 Central America award.

List up to five of your publications in the field of bioanalysis:
1[Shin SR, Kilic T, Zhang YS], Avci H, Hu N, Kim D, Branco C, Aleman J, Massa S, Silvestri A, Kang J, Desalvo A, Hussaini MA, Chae SK, Polini A, Bhise N, Hussain MA, Lee HY, Dokmeci MR and Khademhosseini A. Label-free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes. Advanced Science, 2017, in press. DOI: 10.1002/advs.201600522. (Co-first author)

2 Zhang YS*, Aleman J, Shin SR, Kilic T, Kim D, Shaegh SAM, Massa S, Riahi R, Chae S, Hu N, Avci H, Zhang W, Silvestri A, Manbohi A, Polini A, Calzone G, Shaikh N, Sanati A, Alerasool, P, Bhise N, Budina E, Pourmand A, Skardal A, Shupe T, Bishop C, Dokmeci MR, Atala A and Khademhosseini A*. Multi-Sensor-Integrated Organs-on-Chips Platform for Automated and Continual in situ Monitoring of Organoid Behaviors. Proceedings of the National Academy of Sciences USA, 2017, 114, E2293-E2302. (Co-corresponding author)

3 [Shin SR, Zhang YS, Kim D], Manbohi A, Avci H, Silvestri A, Aleman J, Hu N, Kilic T, Keung W, Righi M, Assawes P, Alhadrami HA, Li RA, Dokmeci MR and Khademhosseini A. Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers. Analytical Chemistry, 2016, 88, 10019-10027. (Co-first author)

4 Zhang YS, Busignani F, Ribas J, Aleman J, Rodrigues TN, Shaegh SAM, Massa S, Rossi CB, Taurino I, Shin SR, Calzone G, Amaratunga GM, Chambers DL, Jabari S, Niu Y, Manoharan V, Dokmeci MR, Carrara S, Demarchi D and Khademhosseini A. Google Glass-Directed Monitoring and Control of Microfluidic Biosensors and Actuators. Scientific Reports, 2016, 6, 22237.

5 Zhang YS, Chang J-B, Alvarez MM, Trujillo-de Santiago G, Aleman J, Batzaya B, Krishnadoss V, Ramanujam AA, Kazemzadeh-Narbat M, Chen F, Tillberg PW, Dokmeci MR, Boyden ES and Khademhosseini A. Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications. Scientific Reports, 2016, 6, 22691.

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