journal article·2020-10-14Open access

Lipid-Bicelle-Coated Microfluidics for Intracellular Delivery with Reduced Fouling

Jason N. Belling, Liv K. Heidenreich, Jae Hyeon Park, Lisa M. Kawakami, Jack Takahashi, Isaura M. Frost, Yao Gong, Thomas D. Young, Joshua A. Jackman, Steven J. Jonas, Nam-Joon Cho, Paul S. Weiss

ACS Applied Materials & Interfaces· Volume 12· Issue 41

Abstract

Innovative technologies for intracellular delivery are ushering in a new era for gene editing, enabling the utilization of a patient's own cells for stem cell and immunotherapies. In particular, cell-squeezing platforms provide unconventional forms of intracellular delivery, deforming cells through microfluidic constrictions to generate transient pores and to enable effective diffusion of biomolecular cargo. While these devices are promising gene-editing platforms, they require frequent maintenance due to the accumulation of cellular debris, limiting their potential for reaching the throughputs necessary for scalable cellular therapies. As these cell-squeezing technologies are improved, there is a need to develop next-generation platforms with higher throughput and longer lifespan, importantly, avoiding the buildup of cell debris and thus channel clogging. Here, we report a versatile strategy to coat the channels of microfluidic devices with lipid bilayers based on noncovalent lipid bicelle technology, which led to substantial improvements in reducing cell adhesion and protein adsorption. The antifouling properties of the lipid bilayer coating were evaluated, including membrane uniformity, passivation against nonspecific protein adsorption, and inhibition of cell attachment against multiple cell types. This surface functionalization approach was applied to coat constricted microfluidic channels for the intracellular delivery of fluorescently labeled dextran and plasmid DNA, demonstrating significant reductions in the accumulation of cell debris. Taken together, our work demonstrates that lipid bicelles are a useful tool to fabricate antifouling lipid bilayer coatings in cell-squeezing devices, resulting in reduced nonspecific fouling and cell clogging to improve performance.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Lipid Membrane Structure and Behavior · RNA Interference and Gene Delivery · Microfluidic and Bio-sensing Technologies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States

Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, United States

Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095, United States

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea

SKKU-UCLA-NTU Precision Biology Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea

Children’s Discovery and Innovation Institute, University of California, Los Angeles, Los Angeles, California 90095, United States

Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States

School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore

Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095, United States

Funding

David Geffen School of Medicine, University of California, Los Angeles · Tower Cancer Research Foundation · NIH Office of the Director · National Heart, Lung, and Blood Institute · National Institute of Dental and Craniofacial Research · National Research Foundation of Korea · National Research Foundation Singapore · National Institute on Drug Abuse · Alex's Lemonade Stand Foundation for Childhood Cancer · National Institutes of Health · Hyundai Hope On Wheels

References (45)

Show source-provided references
1. 10.1038/nature1976410.1038/nature19764 ↗
2. 10.1063/1.366035210.1063/1.3660352 ↗
3. 10.1038/s41586-018-0326-510.1038/s41586-018-0326-5 ↗
4. 10.1021/acs.chemrev.7b0067810.1021/acs.chemrev.7b00678 ↗
5. 10.1073/pnas.121870511010.1073/pnas.1218705110 ↗
6. 10.1038/s41551-017-003910.1038/s41551-017-0039 ↗
7. 10.1002/adbi.20170005410.1002/adbi.201700054 ↗
8. 10.1016/j.mattod.2018.03.00210.1016/j.mattod.2018.03.002 ↗
9. 10.1063/1.366035210.1063/1.3660352 ↗
10. 10.1021/acs.nanolett.9b0284110.1021/acs.nanolett.9b02841 ↗
11. 10.1073/pnas.191712511710.1073/pnas.1917125117 ↗
12. 10.1021/acsnano.9b0793010.1021/acsnano.9b07930 ↗
13. 10.1039/c3ib40215k10.1039/c3ib40215k ↗
14. 10.1039/c7ib00060j10.1039/c7ib00060j ↗
15. 10.1073/pnas.180967111510.1073/pnas.1809671115 ↗
16. 10.1088/1361-6439/ab3e7d10.1088/1361-6439/ab3e7d ↗
17. 10.1002/(SICI)1522-2683(20000101)21:1<107::AID-ELPS107>3.0.CO;2-Y10.1002/(SICI)1522-2683(20000101)21:1<107::AID-ELPS107>3.0.CO;2-Y ↗
18. 10.1002/sia.296410.1002/sia.2964 ↗
19. 10.1002/sia.227410.1002/sia.2274 ↗
20. Lee W. · 2017 · 110.1007/978-3-319-44139-9 ↗
21. 10.1039/b610503c10.1039/b610503c ↗
22. 10.1021/ac053496h10.1021/ac053496h ↗
23. 10.1021/acs.langmuir.9b0057010.1021/acs.langmuir.9b00570 ↗
24. 10.1021/acs.langmuir.9b0164410.1021/acs.langmuir.9b01644 ↗
25. 10.1021/acsami.9b2061710.1021/acsami.9b20617 ↗
26. 10.1021/acs.langmuir.9b0370610.1021/acs.langmuir.9b03706 ↗
27. 10.1021/ac000997o10.1021/ac000997o ↗
28. 10.1002/elps.20030562710.1002/elps.200305627 ↗
29. 10.1073/pnas.04056229710.1073/pnas.040562297 ↗
30. 10.1016/s0022-1759(03)00193-510.1016/s0022-1759(03)00193-5 ↗
31. 10.1021/bm901445r10.1021/bm901445r ↗
32. 10.1002/adhm.20170024310.1002/adhm.201700243 ↗
33. 10.1021/nl204535h10.1021/nl204535h ↗
34. 10.1021/la010481f10.1021/la010481f ↗
35. 10.1002/jbm.a.1044210.1002/jbm.a.10442 ↗
36. 10.1021/acs.langmuir.7b0021010.1021/acs.langmuir.7b00210 ↗
37. 10.1126/science.276.5317.142510.1126/science.276.5317.1425 ↗
38. 10.1002/jbm.1000510.1002/jbm.10005 ↗
39. 10.1006/jcis.2001.806010.1006/jcis.2001.8060 ↗
40. 10.1039/c6sm01879c10.1039/c6sm01879c ↗
41. 10.1038/natrevmats.2017.1610.1038/natrevmats.2017.16 ↗
42. 10.1039/b813516a10.1039/b813516a ↗
43. 10.1126/sciadv.150045410.1126/sciadv.1500454 ↗
44. 10.1021/ja800049f10.1021/ja800049f ↗
45. 10.1073/pnas.140840111110.1073/pnas.1408401111 ↗