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Many clinical procedures and biomedical research workflows rely on microscopy, including diagnosis of cancer, genetic disorders, autoimmune diseases, infections, and quantification of cell culture. Despite its widespread use, traditional image acquisition and review by trained microscopists is often lengthy and expensive, limited to large hospitals or laboratories, precluding use in point‐of‐care settings. In contrast, lensless or lensfree holographic microscopy (LHM) is inexpensive and widely deployable because it can achieve performance comparable to expensive and bulky objective‐based benchtop microscopes while relying on components that cost only a few hundred dollars or less. Lab‐on‐a‐chip integration is practical and enables LHM to be combined with single‐cell isolation, sample mixing, and in‐incubator imaging. Additionally, many manual tasks in conventional microscopy are instead computational in LHM, including image focusing, stitching, and classification. Furthermore, LHM offers a field of view hundreds of times greater than that of conventional microscopy without sacrificing resolution. Here, the basic LHM principles are summarized, as well as recent advances in artificial intelligence integration and enhanced resolution. How LHM is applied to the above clinical and biomedical applications is discussed in detail. Finally, emerging clinical applications, high‐impact areas for future research, and some current challenges facing widespread adoption are identified.
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This content will become publicly available on September 1, 2026
Evaporation and focus degradation mitigation in in-incubator live cell imaging for capacitance lab-on-CMOS microsystem calibration
Lab-on-CMOS is an instrumentation technology that combines miniaturized bioanalytical hardware with complementary metal-oxide semiconductor (CMOS) electronics to provide integrated biosensing in a compact format. This paper focuses on a class of lab-on-CMOS systems that utilize capacitance sensing as a means to monitor cell cultures and track cell proliferation, as well as other cell life-cycle events. In this paradigm, changes in interfacial capacitance result from the activity of adherent cells at a bioelectronic interface. These changes are mapped to cell proliferation or life-cycle events using ground-truth measurements such as live cell imaging from real-time microscopy. This paper identifies instrumentation challenges that arise from conducting these ground-truth measurements in a calibrated cell culture environment, i.e., when the lab-on-CMOS system is deployed inside a CO2 cell culture incubator. In particular, we provide a detailed study of evaporation and focus degradation mitigation techniques for application in-incubator live cell imaging during lab-on-CMOS capacitance sensor calibration tasks. We show that autofocusing the microscopy column and provisioning the lab-on-CMOS with an immersion lid are two approaches that significantly improve the quality of live cell imaging ground-truth measurements over long periods.
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- Award ID(s):
- 2442346
- PAR ID:
- 10655024
- Publisher / Repository:
- AIP
- Date Published:
- Journal Name:
- Review of Scientific Instruments
- Volume:
- 96
- Issue:
- 9
- ISSN:
- 0034-6748
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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