A 3D-printed microfluidic device was developed for testing the combinatorial effects of drugs on patient-derived 3D spheroid tissues cultured under dynamic flow conditions. Figure 1 shows the heterogeneous drug responses observed in three oral cancer patient samples cultured in the device, highlighting the significance of personalized functional drug testing in cancer using tumor-on-chips. The device successfully identified several effective drug combinations for each patient that may be suitable for treatment. Additionally, we identified a few ineffective drug therapies to which the patient samples were resistant.
For more details, kindly refer to the published article in Journal of Nanobiotechnology:
DOI: https://doi.org/10.1186/s12951-024-02625-y
Indian patent (granted): 432209
Figure 1. Live/dead staining after drug perfusion at 2 µl/min for 6 h and 2 h static incubation on day 3: (A) Patient 1 spheroids showing live cells in green and dead cells in red color. (B) Patient 2 spheroids showing live cells in green and dead cells in red color. (C) Patient 3 spheroids showing live cells in green and dead cells in red color. (D) Inter-patient comparison. (Reduced chemosensitivity in a few spheroids in patient 2 and 3 has been shown by small colored squares in the fluorescent images and arrows showing high standard deviation in the bar graph). (All data normalized to control, data presented as Mean±SD, A one-way ANOVA, Tukey’s post hoc test, n=7 spheroids measured for each treatment group, ‘&’ shows p<0.001 with control, ‘#’ shows p<0.05 with control) The spheroids cultured in left-most and right-most microwell arrays have been shown in the horizontal orientation. Controls were treated with 0.1% DMSO. Scale bars in left panels are 100 µm and right magnifed panels are 50 µm (Image credit: Springer Nature publications)
In vitro platform predicting the metastatic potential of patient-derived oral tumor cells has been developed. The device design is inspired from Dr. Kamm's work. However, the use of 3D printing greatly simplified the fabrication procedure and design iteration process. We show the feasibility of real time three-dimensional (3D) tissue-specific invasion of cancer stem like-cells (CSCs) from two different primary tumors employing a microfluidic device. (Figure 2). We report a novel decellularized bone-derived matrix, which induced differential invasion of patient-derived cells. Overall, this work demonstrated that the proposed microfluidic chip with bone-specific ECM can efficiently replicate in vitro biochemical conditions for distinguishing tissue-specific invasive phenotype and screening drug resistance.
For more details, kindly refer to the published article in Chemical Engineering Journal:
DOI: https://doi.org/10.1016/j.cej.2024.151202
Figure 2. Influence of osteo-specific matrix on invasion. (a) Representative image of whole chip shows central gel channel and CSC-like cells in two side channels of on day 5 of culture. Invasion of OCSCs in (b) Col and (c) Os-Col. Invasion of BCSCs in (d) Col and (e) Os-Col. Cells that moved across the hydrogel barrier (denoted as white dotted lines) were defined as invading cells as per ROI. Cells were stained for viability with Calcein-AM/PI. Green depicts live cells, and red depicts dead cells. (f) Number of invading cells in Col and Os-Col. (g) Average migration distance of invading cells in Col and Os-Col. Data represents mean ± standard deviation for n = 5–6 chips with 6 ROIs imaged per chip. *p < 0.05, **p < 0.01, and ***p < 0.001. ‘&’ shows p < 0.01 and ‘#’ shows p < 0.001 between the same cells on two hydrogel groups. OCSCs: enriched cancer stem-like cells derived from oral carcinoma; BCSCs: enriched cancer stem-like cells derived from breast adenocarcinoma. Scale bar = 100 μm. (Image credit: Elsevier publications)
Imagine a versatile and dynamic organ-on-chip device compatible with a variety of 3D tissue models such as 3D spheroids, organoids, biopsy tissues, reconstructed tissues, vascularized tissues, barrier tissues, bioprinted tissues and co-cultures of multiple cells! Imagine a device which can allow access to your cultured tissues for molecular studies! Imagine a device which is very simple to operate, affordable, and doesn't require significant training!
We are currently developing a first of its kind novel patented technology which will include all of the above features in one platform. PCT application has been filed for the device and currently we are looking for potential investors interested in supporting our venture.
Additionally, we are also looking for potential co-founder(s) preferably experienced in organ-on-chips development and passionate about complex in vitro models! Do connect over E-mail or LinkedIn, if you are interested in collaborating with us!