Reply to ‘‘Comment on ‘Digital parallel acquisition in frequency domain fluorometry’ ’’ [Rev. Sci. Instrum. <b>6</b>
                  <b />, 2929 (1989)]

Feddersen, Brett; Piston, David W.; Gratton, Enrico

doi:10.1063/1.1142408

Cited by 17 publications
(23 citation statements)

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“…Of course, the peak power of the light pulses may be quite high. Another system which is disadvantageous with respect to duty ratio is the method of Fedderson, Piston, and Gratton 40 where pulsed light sources of widths of a hundred nanoseconds are used at a frequency of 1 MHz; the duty ratio may be only 10%. Systems employing light pulses are of an intrinsically much greater bandwidth than those employing sinusoids, particularly when the operation of the system depends upon harmonic generation by mixed pulse trains.…”

Section: Duty Ratio Considerationsmentioning
confidence: 99%

“…Bandwidth conservation is not a factor in phase modulation, pulse technology, and broadband harmonic generation is employed in multi-frequency phase fluorometry. 40 DSP naturally fits such technology and may be essential to minimize radio frequency interference or crosstalk. However, in SSB phase modulation ͑PMD͒ systems, DSP technology follows state-of-the-art communication design, as found in some modern amateur radio receivers where DSP is employed at the lower intermediate and audio frequencies.…”

Section: Digital Technology: Digital Signal Processing "Dsp…mentioning
confidence: 99%

“…9; in homodyne systems, the intermodulation signals due to the impingement of the two radio frequency carriers simultaneously upon the detector system can cause significant and complex intermodulation products especially when the transfer characteristic of the second dynode of the PMT is relied upon ͑see elsewhere for this description͒. 40 Such a system can be based on time-sharing technology ͑see Fig. 8͒.…”

Section: E Frequency Encoding Multiplexmentioning
confidence: 99%

“…Optical multiplexing employing light sources of different wavelengths shall cause Ͻ0.03°interchannel crosstalk. ͑e͒ Bandwidth signal output should be variable from 0.2 to 2 Hz or in special cases of brain study, 40 Hz.…”

Section: Performance Criteria Phase Delay Measurement Devices "Pdmd…mentioning
confidence: 99%

“…Then Fourier transformation and filtering are necessary. 40,41 Otherwise, noise bandwidth must be progressively reduced as the signal is amplified. This presents special problems in homodyne system where the noise bandwidth of photodetectors may be Ͼ30 MHz and the overload signal of homodyne detectors is in the millivolt range ͑see below͒.…”

mentioning
confidence: 99%

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Phase measurement of light absorption and scatter in human tissue
Chance
¹
,
Cope
²
,
Gratton
³

et al. 1998
Review of Scientific Instruments
235
0
132
0
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Analog and digital technologies are presented for precise measurement of propagation delay of photons from source and detector placed on portions of the human body. The goal of the apparatus design is to quantify absorption ( a ) and scattering ( s Ј) induced by biological pigments and biological structures, respectively. Body tissues are highly scattering with a mean distance between scatterers of less than a mm ͑at 700-850 nm͒. Significant absorption is mainly due to 5%-10% of the tissue volume occupied by blood. Measurement of a and s Ј is done by both time and frequency domain equipment. This article focuses upon frequency domain equipment because of its simplicity, reduced noise bandwidth, versatility, and the strong analogy to very high frequency/ ultrahigh frequency communication devices, particularly those using phase modulation. Comparisons are made of homodyne and heterodyne systems together with evaluation of single and multiple side band systems, with particular emphasis on methods for multiplexed optical and radio frequencies by frequency encoding or time-sharing technologies. The applications of these phase modulation systems to quantitative brain and muscle blood oximetry, functional activity of the forebrain, and other important problems of medical science, are presented. © 1998 American Institute of Physics. ͓S0034-6748͑98͒01110-1͔ I. BACKGROUND OF THE PROBLEM SET TIME: INTRODUCTION TO THE NATURE OF THE MEDICAL DEVICESThe burgeoning interest in medical devices that are safe, economical, and efficacious, combined with recent observations of the feasibility of time domain optical measurements in human and animal brain, has led to significant interest in, and many publications on, the optical characteristics of human tissues, 1 particularly breast tissue, 2 brain tissue, 3,4 and skeletal muscle. 5 These novel techniques not only allow the measurement of the tissue absorption but also allow the independent measurement of tissue scatter which can also be of great clinical significance. 6,7 Most recently, flow, particularly of blood cells through tissue, can be detected using autocorrelation techniques in the time domain. 8 These reduced transport scattering ( s Ј) and absorption ( a ) parameters are measured in what is termed the near infrared ͑NIR͒ window lying between the declining absorption of blood and the increasing absorption of tissue water in the wavelength region 700-900 nm ͑see Fig. 1͒. In this region, scattering dominates absorption by 2 orders of magnitude and the average distance between isotropic scattering events is approximately 1 mm, while photon propagation pathways in the human head may readily reach 1 m enabling the sampling of large tissue volumes. 9 Thus, measurements at various wavelengths can separate the contributions of the parameters to the total absorption and scattering. For example, for oxy Hb, deoxy Hb, and water three wavelengths will suffice, and since rapidly modulated light is advantageous, laser diodes are most frequently employed as monochromatic light sources at...
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Section: Duty Ratio Considerationsmentioning
confidence: 99%

Section: Digital Technology: Digital Signal Processing "Dsp…mentioning
confidence: 99%

Section: E Frequency Encoding Multiplexmentioning
confidence: 99%

Section: Performance Criteria Phase Delay Measurement Devices "Pdmd…mentioning
confidence: 99%

mentioning
confidence: 99%

See 3 more Smart Citations
Phase measurement of light absorption and scatter in human tissue
Chance
¹
,
Cope
²
,
Gratton
³

et al. 1998
Review of Scientific Instruments
235
0
132
0
View full text Add to dashboard Cite
Analog and digital technologies are presented for precise measurement of propagation delay of photons from source and detector placed on portions of the human body. The goal of the apparatus design is to quantify absorption ( a ) and scattering ( s Ј) induced by biological pigments and biological structures, respectively. Body tissues are highly scattering with a mean distance between scatterers of less than a mm ͑at 700-850 nm͒. Significant absorption is mainly due to 5%-10% of the tissue volume occupied by blood. Measurement of a and s Ј is done by both time and frequency domain equipment. This article focuses upon frequency domain equipment because of its simplicity, reduced noise bandwidth, versatility, and the strong analogy to very high frequency/ ultrahigh frequency communication devices, particularly those using phase modulation. Comparisons are made of homodyne and heterodyne systems together with evaluation of single and multiple side band systems, with particular emphasis on methods for multiplexed optical and radio frequencies by frequency encoding or time-sharing technologies. The applications of these phase modulation systems to quantitative brain and muscle blood oximetry, functional activity of the forebrain, and other important problems of medical science, are presented. © 1998 American Institute of Physics. ͓S0034-6748͑98͒01110-1͔ I. BACKGROUND OF THE PROBLEM SET TIME: INTRODUCTION TO THE NATURE OF THE MEDICAL DEVICESThe burgeoning interest in medical devices that are safe, economical, and efficacious, combined with recent observations of the feasibility of time domain optical measurements in human and animal brain, has led to significant interest in, and many publications on, the optical characteristics of human tissues, 1 particularly breast tissue, 2 brain tissue, 3,4 and skeletal muscle. 5 These novel techniques not only allow the measurement of the tissue absorption but also allow the independent measurement of tissue scatter which can also be of great clinical significance. 6,7 Most recently, flow, particularly of blood cells through tissue, can be detected using autocorrelation techniques in the time domain. 8 These reduced transport scattering ( s Ј) and absorption ( a ) parameters are measured in what is termed the near infrared ͑NIR͒ window lying between the declining absorption of blood and the increasing absorption of tissue water in the wavelength region 700-900 nm ͑see Fig. 1͒. In this region, scattering dominates absorption by 2 orders of magnitude and the average distance between isotropic scattering events is approximately 1 mm, while photon propagation pathways in the human head may readily reach 1 m enabling the sampling of large tissue volumes. 9 Thus, measurements at various wavelengths can separate the contributions of the parameters to the total absorption and scattering. For example, for oxy Hb, deoxy Hb, and water three wavelengths will suffice, and since rapidly modulated light is advantageous, laser diodes are most frequently employed as monochromatic light sources at...
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Widefield multifrequency fluorescence lifetime imaging using a two‐tap complementary metal‐oxide semiconductor camera with lateral electric field charge modulators
Chen
¹
,
Ma
²
,
Kagawa
³

et al. 2019
Journal of Biophotonics
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Widefield frequency‐domain fluorescence lifetime imaging microscopy (FD‐FLIM) measures the fluorescence lifetime of entire images in a fast and efficient manner. We report a widefield FD‐FLIM system based on a complementary metal‐oxide semiconductor camera equipped with two‐tap true correlated double sampling lock‐in pixels and lateral electric field charge modulators. Owing to the fast intrinsic response and modulation of the camera, our system allows parallel multifrequency FLIM in one measurement via fast Fourier transform. We demonstrate that at a fundamental frequency of 20 MHz, 31‐harmonics can be measured with 64 phase images per laser repetition period. As a proof of principle, we analyzed cells transfected with Cerulean and with a construct of Cerulean‐Venus that shows Förster Resonance Energy Transfer at different modulation frequencies. We also tracked the temperature change of living cells via the fluorescence lifetime of Rhodamine B at different frequencies. These results indicate that our widefield multifrequency FD‐FLIM system is a valuable tool in the biomedical field.

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Glucose Sensor for Low-Cost Lifetime-Based Sensing Using a Genetically Engineered Protein
Tolosa
¹
,
Gryczyński
²
,
Eichhorn
³

et al. 1999
Analytical Biochemistry
191
2
157
1
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We describe a glucose sensor based on a mutant glucose/galactose binding protein (GGBP) and phase-modulation fluorometry. The GGBP from Escherichia coli was mutated to contain a single cysteine residue at position 26. When labeled with a sulfhydryl-reactive probe 2-(4'-iodoacetamidoanilino)naphthalene-6-sulfonic acid, the labeled protein displayed a twofold decrease in intensity in response to glucose, with a dissociation constant near 1 microM glucose. The ANS-labeled protein displayed only a modest change in lifetime, precluding lifetime-based sensing of glucose. A modulation sensor was created by combining ANS26-GGBP with a long-lifetime ruthenium (Ru) metal-ligand complex on the surface of the cuvette. Binding of glucose changed the relative intensity of ANS26-GGBP and the Ru complex, resulting in a dramatic change in modulation at a low frequency of 2.1 MHz. Modulation measurements at 2.1 MHz were shown to accurately determine the glucose concentration. These results suggest an approach to glucose sensing with simple devices.

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Reply to ‘‘Comment on ‘Digital parallel acquisition in frequency domain fluorometry’ ’’ [Rev. Sci. Instrum. 6 , 2929 (1989)]

Abstract: The duty cycle problem referred to by Alcala has been discussed in our original manuscript, and we calculated the reduction of the signal quite explicitly. His comments on the harmonic content are in error, and the correct values were given in the original paper.

Cited by 17 publications

References 3 publications

Phase measurement of light absorption and scatter in human tissue

Phase measurement of light absorption and scatter in human tissue

Widefield multifrequency fluorescence lifetime imaging using a two‐tap complementary metal‐oxide semiconductor camera with lateral electric field charge modulators

Glucose Sensor for Low-Cost Lifetime-Based Sensing Using a Genetically Engineered Protein

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