Senior/Postdoctoral Associate - Concentration-Based Detection of Low Abundance Viral and Bacterial...

Project Overview

SMART CAMP (Critical Analytics for Manufacturing Personalized-Medicine) is a new interdisciplinary research programme in Singapore (CREATE international research campus and innovation hub) and at the Massachusetts Institute of Technology (MIT). SMART CAMP addresses key technology bottlenecks in cell therapy manufacturing: (i) critical quality attributes of safe, effective cell therapy products; and (ii) integrated process analytics to monitor and modulate those attributes. While cell therapies are poised to transform healthcare for both the industry and the patient, there remain many outstanding scientific and technical challenges to significant global impact that this R&D programme addresses. This high-impact focus includes measurement and feedback control of processing parameters (process analytic technologies, or PAT) that contribute to cell viability and function during cell proliferation, and the measurement at intermediate and final steps of the cell product properties correlated with positive therapeutic outcomes (critical quality attributes, or CQA).

This interdisciplinary team comprises engineers, biologists, clinicians, manufacturing, and data analytics experts from multiple MIT academic units, and multiple Singapore-based universities, research centres of excellence, and hospitals who are experienced at translational demonstrations of technologies in safety-regulated industries such as cell therapies.

CAMP’s unique, enabling and cross-cutting capabilities include cell and clinical biology, microfluidics, real-time optics and spectroscopies, 3D-printed devices, process analytics, data analytics, and bioinformatics. This programme will demonstrate these approaches required of cell-based personalized medicine through three translational testbeds (three Flagship Projects), ultimately facilitating access for more patients to life-saving, approved cell therapies for currently intractable health challenges. These flagship projects will address allogeneic and autologous cell therapy products, including but not limited to cell sources including adult stem/progenitor cells and immune cells for treatment of specific cancers, tissue degeneration, and autoimmune diseases.

For information on SMART CAMP: https://camp.smart.mit.edu

Job Responsibilities

In the adventitious agent monitoring, it is critical to process relatively large volume (10mL and larger) to collect extremely low abundance targets (e.g. ~1CFU/ml pathogens). This person will develop and integrate general-use sample preparation platform, to be integrated with downstream detectors, including NGS, nanopores, culture-based conventional techniques (for follow-up investigation and validation), and many others. The goal is to significantly (by at least 2-3 orders of magnitudes) increase the detection sensitivity and decrease the assay time by implementing better sample separation and concentration.

DNA-based species identification and detection of extremely low-abundance adventitious agent detection is critical, yet the copy number of target DNA / RNA contained in a relatively large volume of starting sample poses a significant technical hurdle, which is not trivial even for real-time PCR. In this project, we will address by employing a culture-free / amplification-free DNA-PNA hybridization assay, enabled by microfluidic selective preconcentration device.

For more information, see the following reference.

Wei Ouyang, and Jongyoon Han, “Universal amplification-free molecular diagnostics by billion-fold hierarchical nanofluidic concentration,” Proceedings of the National Academy of Sciences of the United States of America (PNAS), 116(33),16240-16249(2019).

Wei Ouyang, Jongyoon Han, “One-Step Nucleic Acid Purification and Noise-Resistant Polymerase Chain Reaction by Electrokinetic Concentration for Ultralow-Abundance Nucleic Acid Detection,” Angewandte Chemie International Edition, 59, 27, 10981-10988, (2020)

• Engineer multi-step preconcentration system for enhanced volume throughput and detection sensitivity
• Engineer better high-throughput preconcentration system for generic sample processing and interfacing with nanopore sequencing / other assays
• Develop a rapid DNA-PNA hybridization assay enabled by multi-step selective preconcentration system.
• Characterize assay characteristics of PNA-based tools to enable their use in a manufacturing setting, by engineering a portable system deployable.
• Development of large-volume preconcentration strategy for sampling 10-100mL volume from bioreactor

Job Requirements

• Ph.D degree in bioengineering, mechanical engineering, electrical engineering and other relevant engineering from a respectable university
• Strong hands-on ability to carry out experimental engineering / instrumentation
• Proven track record of microfluidics and microfabrication
• Creativity to solve challenging technical problem with uncertainty
• Good communication skills to work with researchers from biological / clinical backgrounds
• Good track record of publications and scientific output.
• Able and committed to work in Singapore.

Interested applicants are invited to send in their full CV/resume, cover letter and list of three references (to include reference names and contact information). We regret that only shortlisted candidates will be notified.