## Abstract

Starting with a historical account of evolution in Raman spectroscopy,
in this review we provide details of the advancements that have pushed
detection limits to single molecules and enabled non-invasive
molecular characterization of distinct organelles to provide
next-generation bioanalytical assays and ultrasensitive molecular and
cellular diagnostics. Amidst a growing number of publications in
recent years, there is an unmet need for a consolidated review that
discusses salient aspects of Raman spectroscopy that are broadly
applicable in biosensing ranging from fundamental biology to disease
identification and staging, to drug screening and food and agriculture
quality control. This review offers a discussion across this range of
applications and focuses on the convergent use of Raman spectroscopy,
coupling it to bioanalysis, agriculture, and food quality control,
which can affect human life through biomedical research, drug
discovery, and disease diagnostics. We also highlight how the potent
combination of advanced spectroscopy and machine-learning algorithms
can further advance Raman data analysis, leading to the emergence of
an optical Omics discipline, coined “Ramanomics.”
Finally, we present our perspectives on future needs and
opportunities.

© 2023 Optica Publishing
Group

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### Equations (15)

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(1)
$$P = \alpha \; E,
$$
(2)
$$\left[ {\begin{array}{c}
{{p_x}}\\ {{p_y}}\\ {{p_z}} \end{array}} \right] = \; \left[
{\begin{array}{ccc}
{{\alpha_{xx}}}&{{\alpha_{xy}}}&{{\alpha_{xz}}}\\
{{\alpha_{yx}}}&{{\alpha_{yy}}}&{{\alpha_{yz}}}\\
{{\alpha_{zx}}}&{{\alpha_{zy}}}&{{\alpha_{zz}}} \end{array}}
\right]\left[ {\begin{array}{c} {{E_x}}\\ {{E_y}}\\ {{E_z}}
\end{array}} \right]. $$
(3)
$$P = \alpha \; E = \alpha
{E_0}\; \textrm{cos}\,2\pi {\nu _0}t. $$
(4)
$$q = {q_0}\;
\textrm{cos}\,2\pi {\nu _{vib}}t, $$
(5)
$$\alpha = {\alpha _0} +
{\left( {\frac{{d\alpha }}{{dq}}} \right)_0}q + \; \ldots .
$$
(6)
$$\begin{array}{l} P = \;
\alpha {E_0}\; \textrm{cos}\; 2\pi {\nu _0}t = {\alpha _0}{E_0}\;
\textrm{cos}\; 2\pi {\nu _0}t + {\left( {\frac{{d\alpha }}{{dq}}}
\right)_0}q{E_0}\; \textrm{cos}\; 2\pi {\nu _0}t\\ \;\;\; = {\alpha
_0}{E_0}\; \textrm{cos}\; 2\pi {\nu _0}t + \frac{1}{2}{\left(
{\frac{{d\alpha }}{{dq}}} \right)_0}{q_0}{E_0}[{\{{\textrm{cos}\; 2\pi
({\nu_0} + } {\nu_{vib}}} )t\} \; + \{{\textrm{cos}\; 2\pi ({\nu_0} -
} {\nu _{vib}}) t \}]. \end{array}$$
(7)
$$\scalebox{0.97}{$\displaystyle{\alpha _{ij}} = \mathop \sum
\limits_e \mathop \sum \limits_{v^{\prime\prime}} \left[
{\frac{{{\chi_{g,v}}\textrm{|}{\textrm{D}_{ge}} \cdot
{\textrm{e}_S}\textrm{|}{\chi_{e,v^{\prime\prime}}}{\chi_{e,v^{\prime\prime}}}\textrm{|}{\textrm{D}_{eg}}
\cdot
{\textrm{e}_I}\textrm{|}{\chi_{g,v^{\prime}}}}}{{{E_{e,v^{\prime\prime}}}
- {E_{g,v}} - \hbar {\omega_\textrm{I}}}} +
\frac{{{\chi_{g,v}}\textrm{|}{\textrm{D}_{ge}} \cdot
{\textrm{e}_I}\textrm{|}{\chi_{e,v^{\prime\prime}}}{\chi_{e,v^{\prime\prime}}}\textrm{|}{\textrm{D}_{eg}}
\cdot
{\textrm{e}_S}\textrm{|}{\chi_{g,v^{\prime}}}}}{{{E_{e,v^{\prime\prime}}}
- {E_{g,v}} + \hbar {\omega_\textrm{S}}}}} \right],$}$$
(8)
$$\imath \hbar \frac{\partial
}{{\partial t}}\mathrm{\Psi }({r,R,t} )= ({{\mathbf{H}_0} +
\mathbf{V}(t )} )\mathrm{\Psi }({r,R,t} ), $$
(9)
$$\mathrm{\Psi }({r,R,t} )=
\mathop \sum \limits_{j = 1}^\infty {\chi _{j,v}}({R,t} ){\psi
_j}({r,R} ), $$
(10)
$$\scalebox{0.82}{$\displaystyle\chi _j^{(2 )}({R,t} )=
\frac{1}{{{{({\imath \hbar } )}^2}}}\mathop \sum \limits_e \mathop
\smallint \limits_0^T ds\mathop \smallint \limits_0^s du\; {e^{ -
\imath {H_j}({T - s} )/\hbar }}[{ - {\mathbf{D}_{je}}(R )\cdot
\boldsymbol{E}(s )} ]\; {e^{ - \imath {H_e}({s - u} )/\hbar }}[{ -
{\mathbf{D}_{eg}}(R )\cdot \boldsymbol{E}(u )} ]\; {e^{ - \imath
{H_g}u/\hbar }}\chi _{g,v}^{(0 )}(R,0),$}$$
(11)
$$\frac{{{I_{Stokes}}}}{{{I_{anti - Stokes}}}} \propto
\textrm{exp}\left( {\frac{{hc\mathrm{\Delta }\tilde{\nu }}}{{{k_B}T}}}
\right), $$
(12)
$$\chi _{CARS}^{(3
)}({{\omega_{aS}};{\omega_{pump}}, -
{\omega_{Stokes}},{\omega_{pump}}} )\propto \frac{{{\sigma
_{Raman}}}}{{{\omega _R} - {\omega _{pump}} + {\omega _{Stokes}} +
\imath {\mathrm{\Gamma }_R}}}, $$
(13)
$$A(\nu )=
\frac{{{E_M}(\nu )}}{{{E_0}(\nu )}} = \frac{{\varepsilon -
{\varepsilon _0}}}{{\varepsilon + 2{\varepsilon _0}}}{\left(
{\frac{r}{{r + d}}} \right)^3}. $$
(14)
$${G_{EME}}({{\nu_L},{\nu_s}} )= {|{A({{\nu_L}} )}
|^2}{|{A({{\nu_S}} )} |^2} = {\left|{\frac{{\varepsilon ({\nu_L})
- {\varepsilon_0}}}{{\varepsilon ({\nu_L}) + 2{\varepsilon_0}}}}
\right|^2}{\left|{\frac{{\varepsilon ({\nu_S}) -
{\varepsilon_0}}}{{\varepsilon ({\nu_S}) + 2{\varepsilon_0}}}}
\right|^2}{\left( {\frac{r}{{r + d}}} \right)^{12}}, $$
(15)
$$\textrm{EF} = \left(
{\frac{{{I_{Tip - in}}}}{{{I_{Tip - out}}}} - 1}
\right)\frac{{{A_{FF}}}}{{{A_{NF}}}}, $$