Paper-based microfluidic devices for low-cost medical and agricultural diagnostics

PaperMicrofluidics
Paper is an economical and ubiquitous material that is suitable for developing simple diagnostic tests (e.g., litmus test and pregnancy test) for applications in both developed and developing countries. Currently, however, its use is mostly limited to qualitative detection of a single target analyte. Our goal is to expand the performance of paper-based microfluidic devices by understanding fundamental fluid transport, inventing novel device designs, and improving the limit of detection, ultimately providing affordable diagnostic solutions to people in resource-limited areas.

References
  1. Modha, S.*, Shen, Y.*, Chamouni, H., Mulchandani, A., and Tsutsui, H. (2021) Laser-etched grooves for rapid fluid delivery for a paper-based chemiresistive biosensor. Biosensors and Bioelectronics. 180:113090. doi.org/10.1016/j.bios.2021.113090.
  2. Modha, S., Castro, C., and Tsutsui, H. (2021) Recent developments in flow modeling and fluid control for paper-based microfluidic biosensors. Biosensors and Bioelectronics. 178:113026. doi.org/10.1016/j.bios.2021.113026.
  3. Shen, Y., Modha, S., Tsutsui, H., and Mulchandani, A. (2021) An origami electrical biosensor for multiplexed analyte detection in body fluids. Biosensors and Bioelectronics. 171:112721. doi:10.1016/j.bios.2020.112721.
  4. Kalish, B., Tan, M.K., and Tsutsui, H. (2020) Modifying wicking speeds in paper-based microfluidic devices by laser-etching. Micromachines. 11(8):773. doi:10.3390/mi11080773.
  5. Kalish, B., Zhang, J., Edema, H., Luong, J., Roper, J., Beaudette, C., Echodu, R., and Tsutsui, H. (2020) Distance and microsphere aggregation-based DNA detection in a paper-based microfluidic device. SLAS Technology. 25(1):58-66. doi:10.1177/2472630319887680.

Injectable chromatic nanosensors for in vivo detection

ChromaticSensor
The goal of this research direction is to develop low-cost in vivo sensors that are integrated with food crop plant leaves. If realized, expected advantages of the proposed technology over existing sensors or the paper-based tests include elimination of extensive sample preparation steps (e.g., trimming of plant materials, extraction of nucleotides, proteins, or other target molecules) that are required for in vitro approaches and significant reduction in cost per test due to the elimination of such steps and the sensor substrates. Accordingly, such injectable nanosensors could find widespread use in resource-limited settings. Toward this goal, we employ photo-crosslinked polydiacetylenes (PDAs) that are responsive to external stimuli and exhibit a blue-to-red transition visible to the naked eye. By conjugating single-stranded DNA aptamers or antibodies, we synthesized PDA sensors that can selectively detect agriculturally relevant micronutrients and bacterial pathogens.

References
  1. Wen, J.T., Roper, J.M., and Tsutsui, H. (2018) Polydiacetylene supramolecules: Synthesis, characterization, and emerging applications. Industrical and Engineering Chemistry Research. 57(28):9037-9053. doi:10.1021/acs.iecr.8b00848.
  2. Wen, J., Viravathana, P., Ingel, B., Roper, C., and Tsutsui, H. (2017) Polydiacetylene-coated sensor strip for immunochromatic detection of Xylella fastidiosa subsp. fastidiosa.SLAS Technology. 22(4):406-412. doi:10.1177/2472630316689286.
  3. Wen, J., Bohorquez, K., and Tsutsui, H. (2016) Polydiacetylene-coated polyvinylidene fluoride strip aptasensor for colorimetric detection of zinc(II). Sensors and Actuators B: Chemical. 232:313317. doi:10.1016/j.snb.2016.03.118.

Portable nucleic acid extraction for food crops

Whereas we strive to develop novel biosensors and sensing mechanisms, we also acknowledge critical importance of sample preparation steps on downstream sending and detection outcomes. If samples were not properly prepared, even the best sensor available would fail to detect he target analyte. Quantitative polymerase chain reaction (qPCR) is the gold standard for the detection of many pathogens affecting food crops. However, extracting laboratory-grade nucleic acids from plant samples is challenging due to the robust cell walls. We are developing tools for portable nucleic acid extraction of food crops in the field for on-site pathogen detection.

References

Dynamic suspension culture system for scalable production of human stem cells

StemCells
Stem cells, with their remarkable abilities to self-renew and to differentiate into multiple tissue lineages, hold great promise for regenerative medicine. However, progress towards clinical implementation of stem cell therapy is limited in part by the lack of a robust and scalable system that can cost-effectively produce clinically relevant quality and quantity of stem cells and their therapeutic derivatives. Stirred suspension culture has been identified as one such promising platform due to its ease of use, scalability, automation, process monitoring, and widespread use in the pharmaceutical industry among others. In suspension cultures, stem cells generally lack robust adherence to solid surfaces where properties such as substrate stiffness and nanotopography could be employed to induce mechanotransduction signals. We propose to use fluidic agitation, in particular shear force/stress, as the physical cue to steer the fate of stem cells and aim to develop a novel scalable stem cell culture system.

References
  1. Ghasemian, M., Layton, C., Nampe, D., zur Nieden, N.I., Tsutsui, H., and Princevac, M. (2020) Hydrodynamic characterization within a spinner flask and a rotary wall vessel for stem cell culture. Biochemical Engineering Journal. 157:107533. doi:10.1016/j.bej.2020.107533.
  2. Nampe, D., Joshi, R., Keller, K., zur Nieden, N., and Tsutsui, H. (2017) Impact of fluidic agitation on human pluripotent stem cells in stirred suspension culture. Biotechnology and Bioengineering. 114(9):2109-2120. doi:10.1002/bit.26334.
  3. Nampe, D., and Tsutsui, H. (2013) Engineered micromechanical cues affecting human pluripotent stem cell regulations and fate. Journal of Laboratory Automation. 18(6):482-493. doi:10.1177/2211068213503156

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