»


RAMAN


»


Nonlinear Optical Imaging – Introduction and Pharmaceutical Applications


Andrew L. Fussell1 3 , Antti Isomäki, Ph.D.2


Clare J. Strachan, Ph.D.3* 1


Optical Sciences Group, University of Twente, Enschede, the Netherlands 2Faculty of Medicine, Biomedicum Imaging Unit, University of Helsinki, Finland


Faculty of Pharmacy, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Finland


and Introduction to Nonlinear Optics


Nonlinear optics deals with processes where two or more photons interact with the sample material simultaneously. This is only possible when a high enough number of photons is confined in a small volume, i.e. the intensity of the incident light has to be much higher when compared to linear effects (normal absorption, refractive index). In practice this is made possible using ultrashort laser pulses with durations from picoseconds to femtoseconds. The narrow temporal width limits the interaction time between laser pulses and the target medium. Therefore, they offer a way to precisely probe the medium with reduced risk of optically induced damage. Even more importantly, the energy confined within the narrow optical pulse gives rise to very high light intensities and, thus, ultrashort pulses constitute ideal means for provoking a variety of nonlinear optical phenomena. Since the signal is produced selectively at the focus where the intensity is highest, nonlinear methods offer intrinsic axial sectioning property wellsuited for three-dimensional imaging. In optical microscopy, the two most commonly exploited phenomena are TPEF and SHG. CARS microscopy is yet another emerging nonlinear optical technique which is suitable for imaging various biological and pharmaceutical samples. The energy level diagrams of these processes are illustrated in Fig. 1.


54 | | September/October 2013 - 15TH ANNIVERSARY ISSUE


Abstract


Nonlinear optical imaging is an emerging technology with much potential in pharmaceutical analysis. The technique encompasses a range of optical phenomena, including coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two- photon excited fluorescence (TPEF). The combined potential of these phenomena for pharmaceutical imaging includes chemical and solid- state specificity, high optical spatial and temporal resolution, non- destructive and non-contact analysis, no requirement for labels, and the compatibility with imaging in aqueous and biological environments.


In this article, the theory and practical aspects of nonlinear imaging are briefly introduced and pharmaceutical and biopharmaceutical applications are considered. These include material and dosage form characterization, drug release, and drug and nanoparticle distribution in tissues and within live cells. The advantages and disadvantages of the technique in the context of these analyses are also discussed.


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124  |  Page 125  |  Page 126  |  Page 127  |  Page 128  |  Page 129  |  Page 130  |  Page 131  |  Page 132  |  Page 133  |  Page 134  |  Page 135  |  Page 136  |  Page 137  |  Page 138  |  Page 139  |  Page 140  |  Page 141  |  Page 142  |  Page 143  |  Page 144  |  Page 145  |  Page 146  |  Page 147  |  Page 148  |  Page 149  |  Page 150  |  Page 151  |  Page 152  |  Page 153  |  Page 154  |  Page 155  |  Page 156