RESEARCH ARTICLE

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024) 9 | 1

Optical design of a tunable microneedle array for

photodynamic therapy of metastatic melanomas

Diptayan Dasguptaa, Sonam Berwalb,

Bharpoor Singhc, Neha Khatrid

Abstract: The need for photodynamic therapy is increasing with

the rise of skin cancer melanoma detection. However, low pen-

etration depth of light in the UV range and higher scattering of

skin tissues cause harsh clinical practices and reduced irradi-

ance for the activation of chemicals such as photosensitizers

to facilitate cell necrosis of malignant tumors. In this paper,

a tunable microlens integrated on a microneedle array is de-

signed for variable focusing to reduce melanomas at multiple

sites with an improved intensity for reactive oxygen species

production. A light distribution of 36% percent of the input in-

tensity is achieved at the targeted distance of 4.35 mm for blue

light. Red light attained a light distribution of 13% of the input

intensity at a targeted distance of 6.5 mm. Designing such a

light, delivery-based in-vivo biomedical device is of extreme im-

portance for photodynamic therapy of skin cancer on and beyond

the epidermal tissue layer.

Keywords: Microneedle array; microlens; skin cancer; target

delivery; optical design.

1. INTRODUCTION

Cancer is a major public health issue on a global scale, as evidenced

by the 10 million deaths caused in 2020 (Sung et al., 2021). Amongst

all the types of cancers found in the human body, skin cancer is one

of the most aggressive and lethal forms of cancer that pose a signif-

icant threat to public health due to its ability to resist chemothera-

py and spread to other parts of the body through metastasis. Based

on its origin and certain medical characteristics, skin cancer can be

classied into three general types which include basal cell carcino-

mas, squamous cell carcinomas, and cutaneous melanomas (Naidoo,

Kruger, & Abrahamse, 2018). Basal cell carcinomas and squamous

cell carcinomas are classied as nonmelanocytic skin cancers, and

they do not typically spread to adjacent healthy tissues (Allen, 2000).

In contrast, cutaneous melanomas are considered to be metastatically

invasive, as they can spread and infect nearby healthy tissues (Egger-

mont et al., 2014). Being known to be highly drug-resistant, cutane-

ous melanomas cause low patient survival and a high rate of relapse.

Cutaneous Melanomas usually result from the malignancy of a single

melanocyte or the malfunctioning of dysplastic nevi, which are cells

responsible for producing the melanin pigment and are located in the

deepest regions of the epidermis and the early regions of the dermis

(Naidoo et al., 2018). As skin cancer progresses, metastatic melanoma

develops when cancerous cells from the epidermis spread and invade

Article history:

Received: 01-07-2023

Revised: 13-10-2023

Accepted: 07-11-2023

a Department of Applied Optics

and Photonics, University of

Calcutta, Kolkata 700106, India.

bCSIR-CentralScientic

Instruments Organisation,

Chandigarh 160030, India.

AcademyofScientic&

Innovative Research (AcSIR),

Ghaziabad 201002, India.

cCSIR-CentralScientic

Instruments Organisation,

Chandigarh 160030, India.

dCSIR-CentralScientic

Instruments Organisation,

Chandigarh 160030, India.

AcademyofScientic&

Innovative Research (AcSIR),

Ghaziabad 201002, India.

Corresponding author:

nehakhatri@csio.res.in

RESEARCH ARTICLE Diptayan Dasgupta et al.

2 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

distant organs in the body. As of today’s date, more

than 80% of skin cancer deaths are caused due to

metastatic melanomas (Paluncic et al., 2016).

Photodynamic therapy (PDT) is an immense-

ly crucial method for the treatment of metastatic

melanomas (Naidoo et al., 2018). The procedure

involves a dynamic interaction between photosensi-

tizer (PS), reactive oxygen species (ROS), and light.

PS can be classied into four basic types, which

include porphyrins, phthalocyanines, chlorins and

porphycenes (Abrahamse & Hamblin, 2016). Por-

phyrins are excessively used for PDT applications

as they are known to be very much stable whereas

Phthalocyanines have higher PDT efcacy as they

consist of a diamagnetic metal ion. (Jiang, Shao,

Yang, Wang, & Jia, 2014; Singh et al., 2015). Chlo-

rins have a higher PDT efcacy for basal cell car-

cinomas and squamous cell carcinomas (Calixto,

Bernegossi, De Freitas, Fontana, & Chorilli, 2016).

Porphycenes are isomeric structures of porphyrins

but electronically congured (Ruiz-González et al.,

2013). As depicted in Fig. 1, the PS in action forms

a light-sensitive reaction to the targeted cancer cell

which gets activated by the localization of light at

a suitable wavelength resulting in the formation of

cyto-toxic ROS, including singlet molecular oxy-

gen, hydroxyl radicals, and superoxide anions. ROS

induces photo cytotoxicity by subjecting cancer

cells to oxidative stress, leading to the damage of

their cellular biomolecules, such as lipids, proteins,

and nucleic acids, and causing them to become in-

active. This form of treatment is usually less inva-

sive than conventional forms as it targets specic

cancerous tumor regions based on their stage and

causes limited side effects (Naidoo et al., 2018).

Efcient delivery of photosensitizers and ther-

apeutic light is a critical requirement for effective

photodynamic therapy. However, current delivery

methods, such as intravenous injection of photosensi-

tizers or direct illumination of the skin, have limita-

tions. Intravenous injection can cause photosensitiz-

er accumulation in the circulatory system, leading to

harmful effects on healthy tissues (Zhao et al., 2022).

Light delivery inside the skin tissue is also limited

due to its scattering and absorption. Hence most of

the studies for such applications are based on mi-

croneedle array (MNA) (M. Kim et al., 2016). MNAs

are invasive tools that pierce through the stratum cor-

neum to deliver drugs. The functionality of MNAs

can be classied into two applications: Light-deliv-

ery MNAs and Drug Delivery MNAs (Ganeson et

al., 2023; Li, Zhao, Zhang, Ling, & Zhang, 2022).

Despite the advantages of MNA-mediated trans-

dermal delivery of photosensitizers having been

proved, the delivery method of the other PDT key

element, therapeutic light, is yet to be improved.

For example, most of the clinical practices of PDT

use direct application of the light source onto the

skin tissue causing very high scattering and absorp-

tion inside the stratum corneum, hence reducing ef-

fectiveness (Kim & Darafsheh, 2020). Furthermore,

the penetration depth of the UV light spectrum is

on the lower end, such as for blue light, it is 1 mm

and for red light, it is 4 mm (Ash, Dubec, Donne,

& Bashford, 2017). As a result, limitations of the

photosensitizer effectivity for metastatic melano-

mas occur in depths even more than 4 mm into the

skin tissue. The spectral range spanning from 600

to 1200 nm is commonly referred to as the “optical

window of tissue”. However, it should be noted that

light with wavelengths beyond 800 nm is incapable

of producing singlet oxygen due to its insufcient

energy required to initiate a photodynamic reac-

tion, as opposed to shorter wavelengths (Sharman,

Allen, & Van Lier, 1999; Zhu & Finlay, 2008). Se-

lecting an appropriate light source for Photodynam-

ic Therapy (PDT) can be a challenging task since

no single light source is universally optimal for all

indications, even when employing the same photo-

sensitizer (PS). Factors to consider when making

this choice include PS absorption, the tumor loca-

tion, size, accessibility and tissue characteristics of

the affected area, cost, and size of the light source

(Kim & Darafsheh, 2020).

Several techniques to overcome the issue of

light delivery and performance enhancement of

light particles inside tissues have been reported.

In 2016, Kim et al. rst demonstrated the use of an

optical lens-microneedle array (OMNA) to improve

light delivery in human skin tissues at a wavelength

of 498 nm, extending the penetration depth from

1.3 to 2.5 mm (Kim et al., 2016). In 2018, Wu et

al. proposed a low-cost fabrication process for a

painless and thinner structure of OMNA. They suc-

cessfully demonstrated that OMNA could enhance

the light transmission efciency for light therapy

(Wu, Kono, Takama, & Kim, 2019). They also de-

signed a tunable thickness device consisting of a

micropatterned optical sheet with MNA resulting

in light transmission efciency with reduced pain,

and improved skin care in dermatology (Wu, Taka-

ma, & Kim, 2019). This led to the development of

a height xation device for blue light delivery on a

culture dish and an LED system to conduct the cell

RESEARCH ARTICLE Optical design of a tunable microneedle array…

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024), 9 | 3

apoptosis using an MNA array (Wu et al., 2022).

Furthermore, Zhao et al. proposed a dual-function

dissolvable MNA for delivering light as well as

drugs with reduced therapeutic irradiance resulting

in limited skin damage (Zhao et al., 2022). Yang et

al. demonstrated a deep tissue light enhancement

and delivery system for in vivo photothermal treat-

ment, using gold nanoshells and a fabricated optical

ber needle array with multimodal bers (Yang et

al., 2017). The transportation of visible and near-in-

frared light to interstitial tissues has also been facil-

itated through the application of optical bers and

ber-optic MNAs [(Guo et al., 2015; Okuno et al.,

2013; Robinson et al., 2010)].

In this work, an optical design of a tunable mi-

crolens array integrated into a MNA array is pro-

posed to address the therapeutic challenges asso-

ciated with metastatic melanomas located in deep

tissues beyond the epidermal layer. The design aims

to have multiple focuses of light onto the skin tissue

for multiple underlying tumors with enhanced light

intensity distribution for blue and red light. It was

developed to ensure compliance with the photother-

mal damage benchmark. Furthermore, an optimiza-

tion method is also strategized for this application.

2. DESIGN METHODOLOGY

AND THEORETICAL FORMULATION

In this section, the design methodology of the de-

vice is described with its theoretical formulation.

Section 2.1 describes the human skin model design

for this application. Section 2.2 shows the design

principles of the microlens array (MLA) and MNA.

The entire design procedure of the microlens array

and microneedle array was performed using Zemax

Opticstudio and Solidworks respectively.

2.1. Skin Model

The human skin is identied as an interfacial barrier

from the environment. Light penetration inside skin

tissue is different for different wavelengths. Blue light

gets extinguished within 1 mm inside the tissue lay-

er whereas it is roughly around 4 mm for red light as

shown in the schematic skin model in Fig. 2. The skin

model has scattering properties which lead to light

dispersion and hence, eventually reduces the energy

density with increasing depth. The scattering model

for photons inside tissues is designed using the Hen-

vey-Greenstein scattering function (Ash et al., 2017):

Figure 1. Steps involved in photodynamic therapy. (a) Light is provided to the system which as a

result activates the photosensitizer. (b) This indicated the production of ROS after the PS is excited.

appropriate wavelength, cancer cells undergo oxidative stress, inducing photo cytotoxicity through

the formation of singlet molecular oxygen. This process damages cellular biomolecules like lipids,

proteins, and nucleic acids, rendering the cancer cells inactive.

RESEARCH ARTICLE Diptayan Dasgupta et al.

4 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

(1)

where α is the longitudinal scattering function and

g is the anisotropic factor, ranging from −1 ≤ g ≤ 1,

from backscattering through isotropic scattering

to forward scattering. The longitudinal scattering

function is calculated by (Magnain, Elias, & Frige-

rio, 2008):

(2)

The thickness of each skin layer varies accord-

ing to different body layers (Oltulu, Ince, Kokbu-

dak, Findik, & Kilinc, 2018). The thickness of the

skin affects the effectiveness of PDT in different

regions of the body. Hence depending on the loca-

tion, this can affect the diffusion of light and the

absorption of the photosensitizing agent. The light

diffusion ux is calculated using the below equa-

tion (Magnain et al., 2008):

(3)

where μ = cosӨ and ϖ = s/(k+s). The scatterers

embedded in the medium are characterized by their

absorption and scattering coefcients, respectively,

k and s. F, being the collimating ux, follows Fres-

nel and Snell’s law. P(u,ui) is dened as the phase

function for probability for an incident light with

the direction ui to be scattered in the direction ui

Single and multiple scattering are separated here

and are respectively expressed by the second and

third terms of equation (3).

Figure 2. Thickness model used for skin. Blue light cannot penetrate beyond

1 mm inside the skin whereas red light can penetrate to 4mm inside the tissue.

The optical depth differential (dτ) is factorized

on parameters such as wavelength (λ), skin depth (z)

and directions which are dened by angles (Ө, ф)

and its unit vector u. It is calculated by:

(4)

The incident angle is taken as 0°.

Region Epidermis (μm) Dermis (μm) Total Thickness (μm)

Breast 164.3 5888 6052.3

Scalp 112 .4 3132.8 3245.8

Abdomen 163.3 5 4 9 7.7 5661

Back 116 5717.8 5834

Dorsum of hand 244.8 2538.5 2284

Dorsum of foot 206.4 2363.3 2583

Table 1. Depth chart of skin for different body regions

where PDT can be used (Oltulu e t al., 2018).

RESEARCH ARTICLE Optical design of a tunable microneedle array…

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024), 9 | 5

The dermis contains various sublayers including

the upper blood net, reticular dermis and subcuta-

neous fat. The average depth chart of shin tissue

for different body regions where this model can

be used is shown in Table 1. The tumor size under-

neath the skin layers is classied according to the

Breslow depth which is a helpful measure of how

far melanoma has invaded the body (Marghoob,

Koenig, Bittencourt, Kopf, & Bart, 2000). The stag-

ing of skin cancer melanomas can be classied into

9 levels starting from a depth of less than 0.76 mm,

which makes the melanoma on site to distant metas-

tasis (Iqbal, Biermann, Ali, Zaini, & Metzger, 2019;

Keung & Gershenwald, 2018; Marghoob et al.,

2000). Metastasis describes the spread of melano-

ma throughout the human skin to other parts of the

body. M0, the earliest stage, denotes no evident dis-

tant metastasis whereas M1 metastasis denotes evi-

dent spread or distant metastasis. It is the last stage

or stage IV of melanoma, which can occur at a depth

of more than 4mm into the tissue. Usually, it means

that the melanoma has proliferated the whole body.

PDT dosimetry also plays a crucial role in

reducing melanoma and inducing cell necrosis

(Naidoo et al., 2018; Swavey & Tran, 2013). This

process is complex, as it involves the dynamic in-

teractions of light, photosensitizer, and oxygen. The

clinical efcacy of PDT is determined by multiple

factors, such as the type of dosimetry employed, the

total dose, light exposure time, delivery method,

and fractionation scheme. Furthermore, the char-

acteristics of the cancer type, melanoma spread,

and skin thickness must also be taken into account

(Kim & Darafsheh, 2020). Skin contains various

chromophores with scattering and absorption coef-

cients that strongly depend on the wavelength of

light. The tissue’s scattering properties result from

inherent chromophore attenuation and the size of

particles within the tissue, which dictate the type

of scattering that takes place. This scattering phe-

nomenon causes light dispersion within the tissue,

leading to a gradual reduction in energy density as

depth increases (Ash et al., 2017).

2.2. Microlens and Microneedle Design

The proposed design consists of an 11x11 array of

multifocal microlens and MNA where each micro-

lens corresponds to an MNA structure. As depicted

in Fig 3a, the variation of focal length is construct-

ed in a vertical direction to focus on the subsequent

layers of the skin tissue. The proposed MNA makes

the light focus on multiple tumors, increasing the

effective ROS formation and the accuracy of tu-

mor reduction & elimination for PDT considering

there is enough photosensitizer and ROS present

in the tissue. The focal length of the MLA makes

the illumination area tunable as shown in Fig. 3b.

Increasing the eld of illumination (FOI) results

in a corresponding increase in the spread of light

throughout the skin tissue. The designed MLA and

MNA structure is useful for melanomas or tumors

which occur at a depth of more than 3 cm, where

blue and red light tend to get extinguished or have

limited performances. The microlens array is de-

signed using the following equation (Khatri, Berw-

al, Manjunath, & Singh, 2023):

(5)

Where r is the lens distance concerning the

optics axis and hL is the lens height at the vertex.

For spherically designed MLA, k=0. The radius of

curvature (R) relates to the focal length using the

following equation:

(6)

Microlens

array

Radius of

Curvature (mm)

Back focal

length (mm)

R1 1.3 2.51

R2 1.5 2.90

R3 1.7 3.29

R4 1.9 3.67

R5 2.0 3.87

R6 2.2 4.25

R7 2.4 4.64

R8 2.6 5.03

R9 2.8 5.41

R10 35.80

R11 3.25 6.28

Table 2. Microlens Array Dimensions.

The variable focal length helps in a better dis-

tribution of light radiation inside the skin tissue.

The target design specication of the MLA is listed

in Table 2. The R1-R11 is the specic row number

for which the tunable focal length is presented. The

RESEARCH ARTICLE Diptayan Dasgupta et al.

6 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

proposed MLA and MNA can be produced as a sin-

gle optical element using transparent and durable

materials that do not harm the skin upon applica-

tion. To fulll this criterion, poly-lactic acid (PLA)

is used as a suitable option for the MNA due to its

refractive index of 1.47 and low absorption coef-

cient of 0.014 mm–1 for wavelengths beyond 400 nm.

Fig. 4 and 5 show the structure of the designed de-

vice. The selected light sources are two lasers with

a wavelength of 491 nm and 675 nm with 20 mW

power. To achieve optimal results with PDT, it is

crucial to ensure the light source is suitable for the

target tissue, delivery device, and photosensitizer.

Laser technology is commonly employed for PDT

due to its ability to generate coherent, monochro-

matic light with a narrow bandwidth. The excep-

tional optical power of lasers and their capacity to

produce specic wavelengths make them an excel-

lent choice for matching with particular photosensi-

tizers (Kim & Darafsheh, 2020).

Figure 3. (a) Variation of the tunability is constructed in the vertical direction.

The lenses which appear to be thicker are short focusing whereas the thinner ones are longer

focusingmicrolens.(b)Thefocallengthisalsoafactorforthetotaleldofillumination.

The needle inserts a force of about 2.75-2.8N

which can be calculated by the buckling equation

(He, Chen, & Tang, 2008):

(7)

The maximum or critical force (Pe) is deter-

mined by the modulus of elasticity (E), area mo-

ment of inertia (I), column length (L), and spring

constant (μ).

Figure 4. Close view of the designed microlens

integrated on a microneedle array structure.

RESEARCH ARTICLE Optical design of a tunable microneedle array…

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024), 9 | 7

Figure 5. Design parameters of the microneedle array

ortheeldofviewenhancement.

3. COMPUTATIONAL OPTIMIZATION

AND SIMULATION RESULTS

In this section, the results obtained from this simu-

lation study have been explained, along with an op-

timization strategy. Section 3.1 depicts the overall

optimization procedure whereas section 3.2 depicts

the results obtained.

3.1. Optimization Strategy

An optimization procedure has been shown to

maximize performance, as illustrated in Fig. 6.

The focusing depth is set primarily as the light

on each layer of skin will depend on it. Modu-

lating factors are then dened to set up the op-

timization pathways. This is solely dependent on

Figure 6.Optimizationalgorithmowcharttomaximizetheperformancevariables.

RESEARCH ARTICLE Diptayan Dasgupta et al.

8 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

the application and designated wavelength selec-

tion. The wavefront control system is designed to

enable control of illumination using a ray map-

ping technique, depending on tissue constraints,

thereby improving accuracy in the dosimetry of

the photosensitizer. To achieve optimal pene-

tration depth, a positional optimization system

has been employed to design and set design con-

straints. Two sets of wavelengths, as mentioned

earlier, have been considered to enhance penetra-

tion depth under realistic boundary conditions.

Boundary conditions can be added based on the

selection criteria of light dosimetry and spatial

uniformity of the FOI. The larger the FOI, the

more area is covered. Initially, a system with vari-

able illumination space is obtained. Under this

system, the optimization takes place through two

pathways. The microlens with the lowest and the

highest focal length values contribute to the limits

of depth of eld. Next, ray mapping is performed

to point rays at every skin layer, keeping in mind

the absorption rate of the tissue. The positional

optimization system is used after ray mapping in

order to nd the limits of the rays. It usually gets

reduced with the increase in skin depth. However,

the FOI increases, providing a more diffused area

of illumination, resulting in the reduction of light

intensity. After that, the following step requires

the checking of appropriate wavelength and eld

angles. Upon satisfying the parameters, the sys-

tem gives optimized results. Otherwise, initial

parameters are revised and the optimization

method is performed again.

4. RESULTS AND DISCUSSION

The input laser strikes on the microlens array

produce one beam for each needlepoint in an

11x11 system. The MNA acts as a bridging path-

way device between air and high diffusion & ab-

sorption-enabled skin medium. Insertion of the

MNA is a painless procedure, making the photo-

dynamic process hassle-free with improved per-

formance. Fig. 7 shows the working principle of

the variable focal length system. Fig. 7a denotes

the microlens array schematics used for design

whereas Fig. 7b denotes the variable illumina-

tion scheme after adding the microneedle array.

Simulations were performed on the designed

11x11 array.

Figure 7. (a) schematic of the working principle of a smaller tunable microlens array.

(b) Schematics of the working principle of a smaller proposed design.

The microlens array has a distributed focusing

scheme on the MNA for light penetration at dif-

ferent depths. This results in ROS production at

different skin depths. The targeted depth for blue

light is at 4.35 mm to perform PDT at optimized

results.

The extended depth of eld typically improves

light delivery by increasing the appropriate depth.

At a depth of 4.35 mm, the optical intensity at the

tissue surface is approximately 36% of the input

intensity, and it gradually decreases as the light

penetrates deeper into the skin tissue. Fig. 8a,b

show the detector display at a depth of 2 mm inside

the skin tissue, with lenses at the R1 and R2 posi-

tions illuminating the epidermal layer and beyond.

As the ray path becomes unfocused, the light be-

comes distorted, as shown in Fig. 8c. resulting in

reduced power on the tissue. Fig. 9a depicts tun-

able illumination at a depth of 3.5 mm inside the

skin tissue, and Fig. 9b shows the focused lighting

onto the initial reticular dermal layers. Fig. 10a

demonstrates illumination at the end of the der-

mal layer, where the light is focused by R10 and

R11. In conclusion, this attempt at optical simula-

tion has demonstrated improved light delivery into

skin fold models.

RESEARCH ARTICLE Optical design of a tunable microneedle array…

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024), 9 | 9

Figure 9. (a) Detector display of the designed system for blue light at 3.5 mm

inside the skin tissue. (b) focused image of R3 and R4 at the reticular dermis.

Figure 10. (a) Detector display of the designed system

for blue light at 4.2 mm inside the skin tissue. (b) focused

image of R10 and R11 at the end of the dermal layer.

Figure 8. (a) Detector display of the designed system for blue light at 2 mm inside

the skin tissue. (b) focused image of R1 and R2 at the epidermis. (c) Defocused

image of R1 and R2 at 2.5 mm inside the skin tissue due to variable focal length.

RESEARCH ARTICLE Diptayan Dasgupta et al.

10 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

Red light is capable of penetrating deeper into the

skin compared to other visible wavelengths due to its

low absorption as it propagates through the skin tissue.

Therefore, this property makes it an ideal candidate for

various biomedical applications, including skin thera-

pies and diagnostics. The optical penetration depth of

red light targeted using tunable microlens integrated

MNA array within the skin tissue is 6.5 mm, with an

intensity of 13% of the input source. Fig. 11 depicts

the illumination of red light inside the skin tissue,

demonstrating an enhanced penetration depth. This

improved penetration allows for better visualiza-

tion and targeting of specic structures within the

skin, such as blood vessels and pigmented lesions.

Figure 11. Detector display of the designed system

for red light at 6.5 mm inside the skin tissue.

5. CONCLUSION

Light has a tremendous number of therapeutic val-

ues which are very important for the treatment of

skin cancers. One such example is photodynamic

therapy, where a PS is injected into the body which

gets activated at a certain wavelength after being

absorbed by the tumor. This, as a result, causes

a reduction of the tumor size through ROS pro-

duction and cell necrosis. The scope of this paper

includes:

● A tunable microlens integrated MNA has been

developed with a variable focal length to in-

crease the intensity and penetration depth of tar-

get areas. This design enables a target depth of

up to 4.35 mm with 36% of the input intensity

for blue light and up to 6.5 mm with 13% of the

input intensity for red light.

● Development of the skin model is done to pro-

vide accurate simulation results of light penetra-

tion and irradiance inside the tissue.

● An optimization algorithm is also shown and

applied.

● Furthermore, an in-depth analysis of tumor

stages is also provided.

Although the current study focuses on optimiz-

ing the system to achieve variable light distribution

at maximal intensity within a specic depth, the

design parameters of the system can be tailored to

meet specic requirements based on various factors,

such as optical wavelength, tissue type, therapeutic

depth range, and in-vitro applications. The proposed

system can also be integrated with medical devices,

such as endoscopes. For instance, if necessary, the

optical microneedle array can be attached to a ber

optical probe for coupled laser PDT in interstitial

application. By extending the effective therapeutic

depth, this device can be widely utilized to enhance

the efcacy of existing photo-therapies, including

blue light therapy for antimicrobial treatment and

photodynamic therapy for different types of cancer-

ous lesions inside the body. With the help of state-

of-the-art fabrication techniques, the implementa-

tion of such a scheme would give enhanced optical

performance for modern biomedical applications in

light delivery systems.

RESEARCH ARTICLE Optical design of a tunable microneedle array…

https://doi.org/10.37819/nanofab.009.1795 Nanofabrication (2024), 9 | 11

Declaration of conicting interests

The authors declare that they have no known com-

peting nancial interests or personal relationships

that could have appeared to inuence the work re-

ported in this paper. ♦

REFERENCES

AbrAhAmse, h., & hAmblin, m. r. 2016. “New pho-

tosensitizers for photodynamic therapy”. Bio-

chemical Journal, 473(4), 347-364.

Allen, D. C. (2000). Histopathology reporting:

Springer.

Ash, C., DubeC, m., Donne, K., & bAshforD, T.

2017. “Effect of wavelength and beam width

on penetration in light-tissue interaction using

computational methods”. Lasers in Medical Sci-

ence, 32, 1909-1918.

CAlixTo, G. m. f., berneGossi, J., De freiTAs, l.

m., fonTAnA, C. r., & Chorilli, m. 2016. “Nan-

otechnology-based drug delivery systems for

photodynamic therapy of cancer: a review”.

Molecules, 21(3), 342.

eGGermonT, A. m., ChiArion-sileni, V., Grob, J. J.,

Dummer, r., WolChoK, J. D., sChmiDT, h., …

riChArDs, J. m. (2014). Ipilimumab versus pla-

cebo after complete resection of stage III mel-

anoma: Initial efcacy and safety results from

the EORTC 18071 phase III trial. In: American

Society of Clinical Oncology.

GAneson, K., AliAs, A. h., muruGAiyAh, V., Amir-

ul, A.-A. A., rAmAKrishnA, s., & ViGnesWAri,

s. 2023. “Microneedles for Efcient and Precise

Drug Delivery in Cancer Therapy”. Pharmaceu-

tics, 15(3), 744.

Guo, C., yu, h., fenG, b., GAo, W., yAn, m., ZhAnG,

Z., … liu, s. 2015. “Highly efcient ablation of

metastatic breast cancer using ammonium-tung-

sten-bronze nanocube as a novel 1064 nm-la-

ser-driven photothermal agent”. Biomaterials,

52, 407-416.

he, x., Chen, y., & TAnG, l. (2008). Modeling of

exible needle for haptic insertion simulation.

Paper presented at the 2008 IEEE Conference

on Virtual Environments, Human-Computer In-

terfaces and Measurement Systems.

iqbAl, A., biermAnn, D., Ali, h. m., ZAini, J., &

meTZGer, m. 2019. “Investigating the impact of

tool inertia on machinability of a β-titanium al-

loy using tool deection and acoustic emission”.

Proceedings of the Institution of Mechanical En-

gineers, Part B: Journal of Engineering Manu-

facture, 233(7), 1745-1760.

JiAnG, Z., shAo, J., yAnG, T., WAnG, J., & JiA, l.

2014. “Pharmaceutical development, composi-

tion and quantitative analysis of phthalocyanine

as the photosensitizer for cancer photodynamic

therapy”. Journal of Pharmaceutical and Bio-

medical Analysis, 87, 98-104.

KeunG, e. Z., & GershenWAlD, J. e. 2018. “The

eighth edition American Joint Committee on

Cancer (AJCC) melanoma staging system: im-

plications for melanoma treatment and care”.

Expert Review of Anticancer Therapy, 18(8),

775-784.

KhATri, n., berWAl, s., mAnJunATh, K., & sinGh,

b. 2023. “Optical design and fabrication of

zinc selenide microlens array with extended

depth of focus for biomedical imaging”. Nano-

fabrication, 8.

Kim, m., An, J., Kim, K. s., Choi, m., humAr, m.,

KWoK, s. J., … yun, s. h. 2016. “Optical lens-mi-

croneedle array for percutaneous light delivery”.

Biomedical Optics Express, 7(10), 4220-4227.

Kim, m. m., & DArAfsheh, A. 2020. “Light sourc-

es and dosimetry techniques for photodynam-

ic therapy”. Photochemistry and Photobiology,

96(2), 280-294.

li, x., ZhAo, Z., ZhAnG, m., linG, G., & ZhAnG, P.

2022. “Research progress of microneedles in the

treatment of melanoma”. Journal of Controlled

Release, 348, 6 31- 6 47.

mAGnAin, C., eliAs, m., & friGerio, J.-m. 2008.

“Skin color modeling using the radiative transfer

equation solved by the auxiliary function meth-

od: inverse problem”. JOSA A, 25(7), 1737-1743.

mArGhoob, A. A., KoeniG, K., biTTenCourT, f. V.,

KoPf, A. W., & bArT, r. s. 2000. “Breslow

thickness and Clark level in melanoma: support

for including level in pathology reports and in

American Joint Committee on Cancer Staging”.

Cancer, 88(3), 589-595.

nAiDoo, C., KruGer, C. A., & AbrAhAmse, h. 2018.

“Photodynamic therapy for metastatic melano-

ma treatment: A review”. Technology in Cancer

Research & Treatment, 17, 1533033818791795.

oKuno, T., KATo, s., hATAKeyAmA, y., oKAJimA, J.,

mAruyAmA, s., sAKAmoTo, m., … KoDAmA, T.

2013. “Photothermal therapy of tumors in lymph

nodes using gold nanorods and near-infrared la-

ser light”. Journal of Controlled Release, 172(3),

879-884.

RESEARCH ARTICLE Diptayan Dasgupta et al.

12 | Nanofabrication (2024) 9 https://doi.org/10.37819/nanofab.009.1795

olTulu, P., inCe, b., KoKbuDAK, n., finDiK, s., &

KilinC, f. 2018. “Measurement of epidermis,

dermis, and total skin thicknesses from six dif-

ferent body regions with a new ethical histo-

metric technique”. Turkish Journal of Plastic

Surgery, 26(2), 56.

PAlunCiC, J., KoVACeViC, Z., JAnsson, P. J., KA-

linoWsKi, D., merloT, A. m., huAnG, m. l.-h.,

… riChArDson, D. r. 2016. “Roads to melano-

ma: Key pathways and emerging players in mel-

anoma progression and oncogenic signaling”.

Biochimica et Biophysica Acta (BBA)-Molecular

Cell Research, 1863(4), 770-784.

robinson, J. T., Welsher, K., TAbAKmAn, s. m., sher-

loCK, s. P., WAnG, h., luonG, r., & DAi, h. 2010.

“High performance in vivo near-IR (> 1 μm) im-

aging and photothermal cancer therapy with car-

bon nanotubes”. Nano Research, 3, 779-793.

ruiZ-GonZáleZ, r., ACeDo, P., sánCheZ-GArCíA,

D., nonell, s., CAñeTe, m., sToCKerT, J. C., &

VillAnueVA, A. 2013. “Efcient induction of

apoptosis in HeLa cells by a novel cationic por-

phycene photosensitizer”. European Journal of

Medicinal Chemistry, 63, 401-414.

shArmAn, W. m., Allen, C. m., & VAn lier, J. e.

1999. “Photodynamic therapeutics: basic princi-

ples and clinical applications”. Drug Discovery

Today, 4(11), 507-517.

sinGh, s., AGGArWAl, A., bhuPAThirAJu, n. D.

K., AriAnnA, G., TiWAri, K., & DrAin, C. m.

2015. “Glycosylated porphyrins, phthalocya-

nines, and other porphyrinoids for diagnostics

and therapeutics”. Chemical Reviews, 115(18),

10261-10306.

sunG, h., ferlAy, J., sieGel, r. l., lAVersAnne, m.,

soerJomATArAm, i., JemAl, A., & brAy, f. 2021.

“Global cancer statistics 2020: GLOBOCAN

estimates of incidence and mortality worldwide

for 36 cancers in 185 countries”. CA: a Cancer

Journal for Clinicians, 71(3), 209-249.

sWAVey, s., & TrAn, m. (2013). Porphyrin and

phthalocyanine photosensitizers as PDT agents:

a new modality for the treatment of melanoma.

In Recent Advances in the biology, therapy and

management of melanoma: IntechOpen.

Wu, x., Kono, J., TAKAmA, n., & Kim, b. (2019).

Development of Optical Microlens-Microneedle

Array for Phototherapy. Paper presented at the

Proceedings of JSPE Semestrial Meeting 2019

JSPE Spring Conference.

Wu, x., PArK, J., ChoW, s. y. A., KAsuyA, m. C.

Z., iKeuChi, y., & Kim, b. 2022. “Localised light

delivery on melanoma cells using optical mi-

croneed les”. Biomedical Optics Express, 13(2),

1045-1060.

Wu, x., TAKAmA, n., & Kim, b. (2019). A biodegrad-

able microneedles-trapezoidal micropatterned

patch in the LED therapy. Paper presented at the

2019 IEEE CPMT Symposium Japan (ICSJ).

yAnG, T. D., PArK, K., Kim, h.-J., im, n.-r., Kim, b.,

Kim, T., … Choi, y. 2017. “In vivo photothermal

treatment with real-time monitoring by optical

ber-needle array”. Biomedical Optics Express,

8(7), 3482-3492.

ZhAo, h., WAnG, x., GenG, Z., liAnG, n., li, q., hu,

x., & Wei, Z. 2022. “Dual-function microneedle

array for efcient photodynamic therapy with

transdermal co-delivered light and photosensi-

tizers”. Lab on a Chip, 22(23), 4521-4530.

Zhu, T. C., & finlAy, J. C. 2008. “The role of photo-

dynamic therapy (PDT) physics”. Medical Phys-

ics, 35(7Part1), 3127-3136.

Publisher’s note: Eurasia Academic Publishing Group (EAPG) remains neutral

withregardtojurisdictionalclaimsinpublishedmapsandinstitutionalafliations.

Open Access. This article is licensed under a Creative Commons Attribution-NoDerivatives 4.0

International (CC BY-ND 4.0) licence, which permits copy and redistribute the material in any me-

dium or format for any purpose, even commercially. The licensor cannot revoke these freedoms as

long as you follow the licence terms. Under the following terms you must give appropriate credit,

provide a link to the license, and indicate if changes were made. You may do so in any reasonable

manner, but not in any way that suggests the licensor endorsed you or your use. If you remix,

transform,orbuilduponthematerial,youmaynotdistributethemodiedmaterial.Toviewacopy

of this license, visit https://creativecommons.org/licenses/by-nd/4.0/.