Research

Our laboratory develops microphysiological systems using microfluidics to model non-small cell lung cancer (NSCLC) and support personalized therapeutic strategies. These platforms are engineered to evaluate drug responses to EGFR and KRAS G12C inhibitors using patient-derived organoids (PDOs), which are cultured in standardized microwell formats to ensure consistent analysis. By enabling quantitative assessment of drug efficacy, these systems have contributed to studies addressing both intrinsic and acquired resistance to EGFR tyrosine kinase inhibitors and have facilitated investigations into KRAS-targeted therapies in lung and pancreatic cancers. Recent efforts include the development of microfluidic chips for high-throughput drug screening and the characterization of resistance mechanisms in KRAS G12C and KRAS G12D mutant disease. These technologies are compatible with clinical samples and integrate seamlessly with downstream analytical tools such as molecular profiling, imaging, and cytometry, advancing cancer-on-chip approaches for translational oncology.

1. I. Pulido, L. Gunder, C. Ying, Y. Wang, Y. Dai, Z. Yang, A. Rahnama, J .Li, Y. Sun, C. Li, H. Zhou, G. Wang, K. Foley, K. Abdelhady, M. Massad, T. Prince, I. Papautsky, W. Ying, T. Shimamura. “Dual Inhibitors of KRASG12D and HSP90 are Effective Against KRAS G12D Inhibitor Resistance.” Molecular Cancer Therapeutics 2025. doi:10.1158/1535-7163.MCT-24-1173.
2. I. Pulido, Q. Luan, S. Pastor-Puente, L. Gunder, Y. Wang, C. Ying, J. Li, Y. Sun, Y. Dai, G. Wang, K. Foley, W. Ying, I. Papautsky, J. Carretero, T. Shimamura, “Chaperone directed heterobifunctional molecules circumvent KRASG12C inhibitor resistance,” Cancer Letters 2025, 622, 217691. doi:10.1016/j.canlet.2025.217691
3. Q. Luan, I. Pulido, A. Isagirrea, J. Carreterod, J. Zhou, T. Shimamura, I. Papautsky, “Deciphering fibroblast-induced drug resistance in nonsmall cell lung carcinoma through patient-derived organoids in agarose microwells,” Lab Chip 2024, 24(7), 2025-2038. doi: 10.1039/D3LC01044A
4. Q. Luan, J. H. Becker, C. Macaraniag, M. G. Massad, J. Zhou, T. Shimamura, I. Papautsky, “Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies,” Lab Chip, 2022, 22, 2364-2375. doi: 10.1039/D2LC00244B

Inertial microfluidics is a label-free technique that utilizes hydrodynamic forces within microchannels to focus and separate cells based on size, shape, and deformability. This approach relies on the interplay of shear-induced lift and wall effects, which drive lateral migration of cells to equilibrium positions across streamlines. Our research has advanced the fundamental understanding of these mechanisms through high-speed imaging and experimental studies in straight, spiral, and serpentine channels. While conventional inertial devices typically support bimodal separation, we are developing platforms capable of continuous, multi-modal sorting with tunable cutoff diameters. These innovations enable precise manipulation of complex cell mixtures and facilitate integration with downstream detection methods, expanding the utility of inertial microfluidics in cytometry, liquid biopsy, and systems biology.

1. M. M. Naderi, H. Gao, J. Zhou, I. Papautsky, and Z. Peng, “Deciphering the unique inertial focusing behavior of sperm cells.” Lab Chip, 2025, 25, 2874. doi: 10.1039/d5lc00047e
2. G. Lauricella, M. Naderi, J. Zhou, I. Papautsky, and Z. Peng. “Reversed equilibrium bifurcation for ellipsoidal particles in inertial shear flows between two walls,” Journal of Fluid Mechanics. 2024, 984, A47. doi: 10.1017/jfm.2024.152
3. J. Zhou, P. Mukherjee, H. Gao, Q. Luan, and I. Papautsky, “Label-free microfluidic sorting of microparticles,” APL Bioengineering, 3, 041504, 2019.  doi: 10.1063/1.5120501
4.  J. Zhou, I. Papautsky, “Viscoelastic microfluidics: progress and challenges,” Microsystems & Nanoengineering, 2020, 6 (1), 1-24. doi: 10.1038/s41378-020-00218-x
5. J. Zhou and I. Papautsky, “Fundamentals of inertial focusing in microchannels” Lab Chip, 2013, 13: 1121. doi: 10.1039/C2LC41248A

We apply inertial microfluidic principles to develop label-free, high-throughput platforms for isolating circulating tumor cells (CTCs) from whole blood, enabling non-invasive cancer diagnostics through liquid biopsy. These devices operate passively, without external fields or power, and exploit size-based inertial effects to separate CTCs (>15 µm) from smaller blood cells such as red and white blood cells. Our systems achieve high purity (>95%) and rapid processing rates (up to 2 mL/min), making them suitable for clinical workflows. In addition to isolating individual CTCs for molecular analysis, our platforms capture circulating tumor microemboli and cell clusters, which are increasingly recognized for their role in cancer progression. Integration with downstream tools such as sequencing and imaging enhances the utility of these devices in personalized oncology.

1. C. Macaraniag, I. Khan, A. Barabanova, V. Valle, J. Zhou, P. C. Giulianotti, A. Borgeat, G. Votta-Velis, I. Papautsky, “Benchmarking microfluidic and immunomagnetic platforms for isolating circulating tumor cells in pancreatic cancer.” Lab Chip, 2025, 25, 5292-5301. doi: 10.1039/d5lc00512d
2. C. Macaraniag, J. Zhou, J. Li, W. Putzbach, N. Hay, I. Papautsky, “Microfluidic isolation of breast cancer circulating tumor cells from microvolumes of mouse blood.” Electrophoresis. 2023 Dec;44(23):1859-1867. doi: 10.1002/elps.202300108
3. J. Zhou, A. Kulasinghe, A. Bogseth, K. O’Byrne, C. Punyadeera, and I. Papautsky, “Isolation of circulating tumor cells in non-small-cell-lung-cancer (NSCLC) patients using a multi-flow microfluidic channel”, Microsystems & Nanoengineering, 2019, 5, 8.  doi: 10.1038/s41378-019-0045-6
4. A. Kulasinghe, J. Zhou, L. Kenny, I. Papautsky,and C. Punyadeera, “Capture of circulating tumour cell clusters using straight microfluidic chip,” Cancers, 2019, 11(1), 89.  doi: 10.3390/cancers11010089

Blood fractionation is essential for clinical diagnostics and biomedical research, enabling targeted analysis of specific cellular components. Our lab develops compact spiral inertial microfluidic devices that achieve label-free, continuous separation of blood cell populations with high throughput and efficiency. These systems utilize hydrodynamic lift forces and secondary Dean flows within curved microchannels to focus and sort cells based on physical properties. Optimized spiral designs enable high-throughput processing (1–2 mL/min) with high separation efficiency (>95%) in small device footprints (<1 in²), even at physiological hematocrit levels. Our platforms also support sheathless cytometry, preserving fragile or rare cells by minimizing shear stress. Recent innovations using viscoelastic fluids allow direct cell isolation from whole blood without dilution, simplifying sample preparation. These capabilities support integration with downstream analyses such as flow cytometry, molecular assays, and imaging, paving the way for point-of-care blood diagnostics.

1. J. Zhou and I. Papautsky, “Size-dependent enrichment of leukocytes from undiluted whole blood using shear-induced diffusion”, Lab Chip, 19, 3416-3426, 2019. doi: 10.1039/C9LC00786E
2. J. Zhou, C. Tu, Y. Liang, B. Huang, Y. Fang, X. Liang, I. Papautsky, and X. Ye, “Isolation of cells from whole blood using shear-induced diffusion,” Scientific Reports, 2018, 8, 9411.  doi: 10.1038/s41598-018-27779-2
3.  N. Nivedita, N. Garg, A. P. Lee and I. Papautsky, “A high throughput microfluidic platform for size-selective enrichment of cell populations in tissue and blood samples,” Analyst, 2017, 142, 2558-2569.  doi: 10.1039/C7AN00290D
4. N. Nivedita and I. Papautsky, “Continuous separation of blood cells in spiral microfluidic devices,” Biomicrofluidics, 2013, 7: 054101. doi: 10.1063/1.4819275

In earlier research, our lab developed point-of-care electrochemical sensors for rapid detection of trace metals such as lead (Pb), manganese (Mn), cadmium (Cd), and zinc (Zn) in biological fluids and environmental water samples. These sensors employed anodic and cathodic stripping voltammetry and were miniaturized into USB-stick form factors for field deployment. Initial designs featured bismuth electrodes, later replaced by copper-based systems to reduce cost and improve stability. This approach demonstrated high sensitivity and low detection limits, offering a promising solution for on-site exposure assessment in vulnerable populations. To expand biosensing capabilities, we explored electrochemical impedance spectroscopy (EIS) as a sensitive method for detecting biomolecules. EIS sensors typically use interdigitated electrode arrays (IDAs) functionalized with bio-recognition elements such as antibodies, peptides, or aptamers. Target binding induces changes in impedance, which can be quantified through Faradaic measurements. Our recent work demonstrated the use of EIS for detecting the neurotransmitter Orexin A at picomolar concentrations. Although this research thrust is no longer active, it laid important groundwork for integrating electrochemistry and microfluidics in the development of low-cost, multiplexed biosensors for global health and environmental monitoring.

1. C. Kim, T. J. Hilbert, K. J. Brunst, A. A. Mangino, W. J. Christian, P. J. Parsons, C. D. Palmer, J. Landero, S. Westneat, I. Papautsky, K. N. Dietrich, E. N. Haynes, “Impact of manganese and metal mixtures in blood, hair, and soil on child adaptive behaviors in Southeast Side Chicago.” Environmental Research, 2025, 278, 121637. doi: 10.1016/j.envres.2025.121637
2. E. Boselli, Z. Wu, EN Haynes, I. Papautsky, “Screen-Printed Sensors Modified with Nafion and Mesoporous Carbon for Electrochemical Detection of Lead in Blood.” J Electrochem Soc. 2024 Feb 1;171(2):027513. doi: 10.1149/1945-7111/ad2397
3. A. Friedman, E. Boselli, Y. Ogneva-Himmelberger, W. Heiger-Bernays, P. Brochu, M. Burgess, S. Schildroth, A. Denehy, T. Downs, I. Papautsky, B. Clauss Henn, “Manganese in residential drinking water from a community initiated case study in Massachusetts,” Journal of Exposure Science & Environmental Epidemiology; 34, 58-67. doi: 10.1038/s41370-023-00563-9
4. Z. Zhang, E. Boselli, I. Papautsky, “Potentiometric Sensor System with Self-Calibration for Long-Term, In Situ Measurements.” Chemosensors 2023, 11, 48. doi: 10.3390/chemosensors11010048
5. C. Andreasi Bassi, Z. Wu, L. Forst, and I. Papautsky, “Determination of Mercury with a Miniature Sensor for Point-of-care Testing,” Electroanalysis, 34, 2022. doi.org/10.1002/elan.202200234