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Nonlinear photoacoustic signal amplification from single targets in absorption background.

Sarimollaoglu M, Nedosekin DA, Menyaev YA, Juratli MA, Zharov VP - Photoacoustics (2014)

Bottom Line: This approach was demonstrated by using nonlinear PA flow cytometry platform for label-free detection of circulating melanoma cells in blood background in vitro and in vivo.Nonlinearly amplified PA signals from overheated melanin nanoclusters in melanoma cells became detectable above still linear blood background.Nonlinear nanobubble-based photoacoustics provide new opportunities to significantly (5-20-fold) increase PA contrast of single nanoparticles, cells, viruses and bacteria in complex biological environments.

View Article: PubMed Central - PubMed

Affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.

ABSTRACT
Photoacoustic (PA) detection of single absorbing targets such as nanoparticles or cells can be limited by absorption background. We show here that this problem can be overcome by using the nonlinear photoacoustics based on the differences in PA signal dependences on the laser energy from targets and background. Among different nonlinear phenomena, we focused on laser generation of nanobubbles as more efficient PA signal amplifiers from strongly absorbing, highly localized targets in the presence of spatially homogenous absorption background generating linear signals only. This approach was demonstrated by using nonlinear PA flow cytometry platform for label-free detection of circulating melanoma cells in blood background in vitro and in vivo. Nonlinearly amplified PA signals from overheated melanin nanoclusters in melanoma cells became detectable above still linear blood background. Nonlinear nanobubble-based photoacoustics provide new opportunities to significantly (5-20-fold) increase PA contrast of single nanoparticles, cells, viruses and bacteria in complex biological environments.

No MeSH data available.


Related in: MedlinePlus

Percentage of melanoma cell population that is detectable as function of laser fluence, under static conditions. The threshold for detection was set to mean + 3σ of the PA signals from background (PBS or blood). Bars are mean ± σ.
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fig0030: Percentage of melanoma cell population that is detectable as function of laser fluence, under static conditions. The threshold for detection was set to mean + 3σ of the PA signals from background (PBS or blood). Bars are mean ± σ.

Mentions: Detection thresholds of laser energy fluence, where the PA signals from cells exceed mean + 3σ of the PA signals from background (PBS or blood), are listed in Table 1. The data in this table reflect the presence of at least one cell producing signal above a given threshold (i.e., it is not directly comparable to Fig. 5). All cells that produce signals above threshold were then counted, and plotted in Fig. 6 as percentage of cell population that is detectable as function of laser fluence. When the signals of first laser pulses at each energy level were considered (i.e., no averaging), the detection thresholds were higher than the thresholds observed from averaged signals (Table 1). Averaging consecutive A-line signals reduced the random noise and background level from PBS, hence increased the SBR. When the background medium was blood, however, signals from blood was not diminished. As a result, for a given fluence, increase in SBR for cells in PBS was larger than those in blood. Background curves from PBS and blood are similar in Fig. 5a and c, but after averaging, the gap between curves of cells and background is smaller for blood (Fig. 5b and d). This effect is also visible in Fig. 6, as the improvement in detection by averaging only is better for cells in PBS than the cells in blood. For instance, when the medium-pigmented cells are considered, detection threshold in blood drops from 294 (N = 1) to 224 mJ/cm2 (N = 100). In comparison, detection threshold in PBS drops from 294 to 50 mJ/cm2, indicating ∼3-fold difference in improvement by averaging. On the other hand, when PT bleaching occurs and PA signals are not constant anymore, excessive averaging does not help to improve the SBR. This effect was observed in Fig. 5b and d, as distorted signals at highest fluences. These points were excluded from regression and indicated by dashed lines.


Nonlinear photoacoustic signal amplification from single targets in absorption background.

Sarimollaoglu M, Nedosekin DA, Menyaev YA, Juratli MA, Zharov VP - Photoacoustics (2014)

Percentage of melanoma cell population that is detectable as function of laser fluence, under static conditions. The threshold for detection was set to mean + 3σ of the PA signals from background (PBS or blood). Bars are mean ± σ.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048727&req=5

fig0030: Percentage of melanoma cell population that is detectable as function of laser fluence, under static conditions. The threshold for detection was set to mean + 3σ of the PA signals from background (PBS or blood). Bars are mean ± σ.
Mentions: Detection thresholds of laser energy fluence, where the PA signals from cells exceed mean + 3σ of the PA signals from background (PBS or blood), are listed in Table 1. The data in this table reflect the presence of at least one cell producing signal above a given threshold (i.e., it is not directly comparable to Fig. 5). All cells that produce signals above threshold were then counted, and plotted in Fig. 6 as percentage of cell population that is detectable as function of laser fluence. When the signals of first laser pulses at each energy level were considered (i.e., no averaging), the detection thresholds were higher than the thresholds observed from averaged signals (Table 1). Averaging consecutive A-line signals reduced the random noise and background level from PBS, hence increased the SBR. When the background medium was blood, however, signals from blood was not diminished. As a result, for a given fluence, increase in SBR for cells in PBS was larger than those in blood. Background curves from PBS and blood are similar in Fig. 5a and c, but after averaging, the gap between curves of cells and background is smaller for blood (Fig. 5b and d). This effect is also visible in Fig. 6, as the improvement in detection by averaging only is better for cells in PBS than the cells in blood. For instance, when the medium-pigmented cells are considered, detection threshold in blood drops from 294 (N = 1) to 224 mJ/cm2 (N = 100). In comparison, detection threshold in PBS drops from 294 to 50 mJ/cm2, indicating ∼3-fold difference in improvement by averaging. On the other hand, when PT bleaching occurs and PA signals are not constant anymore, excessive averaging does not help to improve the SBR. This effect was observed in Fig. 5b and d, as distorted signals at highest fluences. These points were excluded from regression and indicated by dashed lines.

Bottom Line: This approach was demonstrated by using nonlinear PA flow cytometry platform for label-free detection of circulating melanoma cells in blood background in vitro and in vivo.Nonlinearly amplified PA signals from overheated melanin nanoclusters in melanoma cells became detectable above still linear blood background.Nonlinear nanobubble-based photoacoustics provide new opportunities to significantly (5-20-fold) increase PA contrast of single nanoparticles, cells, viruses and bacteria in complex biological environments.

View Article: PubMed Central - PubMed

Affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR USA 72205.

ABSTRACT
Photoacoustic (PA) detection of single absorbing targets such as nanoparticles or cells can be limited by absorption background. We show here that this problem can be overcome by using the nonlinear photoacoustics based on the differences in PA signal dependences on the laser energy from targets and background. Among different nonlinear phenomena, we focused on laser generation of nanobubbles as more efficient PA signal amplifiers from strongly absorbing, highly localized targets in the presence of spatially homogenous absorption background generating linear signals only. This approach was demonstrated by using nonlinear PA flow cytometry platform for label-free detection of circulating melanoma cells in blood background in vitro and in vivo. Nonlinearly amplified PA signals from overheated melanin nanoclusters in melanoma cells became detectable above still linear blood background. Nonlinear nanobubble-based photoacoustics provide new opportunities to significantly (5-20-fold) increase PA contrast of single nanoparticles, cells, viruses and bacteria in complex biological environments.

No MeSH data available.


Related in: MedlinePlus