Abstract
Fluorescence spectroscopy has become a prominent research tool with wide applications in medical diagnostics and bio-imaging. However, the realization of combined high-performance, portable, and low-cost spectroscopic sensors still remains a challenge, which has limited the technique to the laboratories. A fluorescence lifetime measurement seeks to obtain the characteristic lifetime from the fluorescence decay profile. Time-correlated single photon counting (TCSPC) and time-gated techniques are two key variations of time-resolved measurements. However, commercial time-resolved analysis systems typically contain complex optics and discrete electronic components, which lead to bulkiness and a high cost. These two limitations can be significantly mitigated using contact sensing and complementary metal-oxide-semiconductor (CMOS) implementation. Contact sensing simplifies the optics, whereas CMOS technology enables on-chip, arrayed detection and signal processing, significantly reducing size and power consumption. This paper examines recent advances in contact sensing and CMOS time-resolved circuits for the realization of fully integrated fluorescence lifetime measurement microsystems. The high level of performance from recently reported prototypes suggests that the CMOS-based contact sensing microsystems are emerging as sound technologies for application-specific, low-cost, and portable time-resolved diagnostic devices.
Highlights
Fluorescence spectroscopy and microscopy have been ubiquitous research tools, serving a variety of applications ranging from biomedical diagnostics [1,2,3,4,5] to bio-imaging such as cellular [6,7,8] and molecular imaging [9,10]
Time-resolved fluorescence measurement is a technique where the fluorescence decay profile is recorded with high temporal resolution after a pulsed excitation
We present a study of recent advances in complementary metal-oxide-semiconductor (CMOS) fluorescence lifetime analytic microsystems, in which the combination of contact sensing and time-resolved circuits are expected to play a key role on the roadmap of application-specific, low-cost, and portable diagnostic devices
Summary
Fluorescence spectroscopy and microscopy have been ubiquitous research tools, serving a variety of applications ranging from biomedical diagnostics [1,2,3,4,5] to bio-imaging such as cellular [6,7,8] and molecular imaging [9,10]. Time-resolved fluorescence measurement is a technique where the fluorescence decay profile is recorded with high temporal resolution after a pulsed excitation. A wide variety of FLM instruments are commercially available They are typically bulky and expensive, targeting bench-top, laboratory-based applications [18,19]. Efficient contact sensing systems have been demonstrated covering widespread applications, such as cell manipulation process [22], high-resolution imaging [23], and detecting cellular functions at the single-cell level [24]. We present a study of recent advances in CMOS fluorescence lifetime analytic microsystems, in which the combination of contact sensing and time-resolved circuits are expected to play a key role on the roadmap of application-specific, low-cost, and portable diagnostic devices.
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