The Simple Sensor that Can Save Millions of Lives

[Music]

hello everyone

i’m here today to talk about the reed

platform technology

it’s a handheld point of care technology

for

rapidly assessing a patient’s response

to sepsis

towards enhancing sepsis outcomes

through

clinical evidence-based management

and how do we go about doing this this

is an extremely complex idea and i’m

going to

unpack this for you and in order to do

that i have to take you back

to the very beginning this is back in

2005

where i was a young assistant professor

trying to set up my own research

lab and portland oregon and i was trying

to

find problems that could transform the

way the human

experience went and to enhance the

quality

of care for life i kept thinking about

this

consistently and as i was a sensor

designer

thought about problems where my sensor

design

would change the way human life

interacted with technology

i found a group of clinicians and they

were very much

interested in looking at designing a

blood test

that could help them screen for patients

who come to them with arteriosclerosis

prior to surgery to figure out if the

patient

had vulnerable cardiovascular plaque or

whether it was

stable arthrosclerotic plaque what

exactly am i talking about

our arteries are the major blood vessels

that carry

oxygen-rich blood from our heart to the

rest of the body

and like plumbing of water pipes

they get sometimes clogged they get

coated with material

which is basically made of lipids

cholesterol proteins

which basically clog those pipes so

the way to treat it through surgery is

basically

what’s known as an angioplasty or you

have a stent

so to clean up those pipes but before

the surgery

you want to know if you’re if you are

the physician

whether that arterial wall is going to

remain stable

post-surgery or is going to collapse or

deform

and this depended on the type of plaque

that formed

so if it was stable black then the wall

would stay the way it was

the patient would have a good surgery

and nothing would happen which was

adverse

but if that plaque was unstable then

that wall would collapse

and the patient would die and have an

adverse outcome

so clearly figuring out the proteins

that would help us do this blood test

very quickly before the patient went

into surgery

would help with the outcome so we spent

about three years trying to figure out

what proteins to look

for and we tried quite a few things we

never could find

the exact ones which work like the

indicators on our automobiles

that tell us to turn left or right

similarly we could never find the

proteins here

that told us okay if you measure these

and these are elevated

then you have vulnerable plaque versus

stable black

so we had to abandon the problem after

three years with a bunch of publications

but no technology

to boast about so now fast forward to

2008

and here i am now in phoenix arizona

and met a bioengineer and he had

developed

the single chain fragments which are

again

proteins engineered proteins and we were

trying to look

to distinguish between three different

types of proteins that could be there

in our brain to distinguish between

alzheimer’s disease

parkinson’s disease and dementia with

the lewy body

so now again mostly these proteins would

be prevalent

within the brain and then it would seep

down

through the cerebrospinal fluid which

goes around the brain and the spinal

cord

cord and you’d be trying to look for

them

so we thought we engineered a very

sensitive test

that could look at one part of the y

that you see there

binding to the proteins and different

proteins on the same sensor

now the problem is the following getting

access to the cerebrospinal fluid

is tough so getting access is going to

require you to do a spinal tap for a

patient

no one likes that it’s very difficult to

do

and it’s painful it can have adverse

outcomes to the patient

so clearly that’s not going to work the

second thing is we couldn’t access this

in healthy or in human subjects we could

only get them

in postmortem so dead people so no point

building a test

on that for dead people so you have to

do it for people who are alive

where you can change their life so two

lessons learned first from the

study in portland and here in arizona

you have to

find the right protein or the right bio

marker to go after

second you have to build an ultra

sensitive test

on fluids or body fluids that are easily

accessible

like your blood through a finger prick

so with both these ideas in mind

i decided to go for the next generation

of the sensor technology

to address this but before i could do

any of that my professional and personal

life

hit a major roadblock and the year was

2010

and the month was april i was a new mom

and i was trying to just get used to the

fact that i had a young baby to take

care of

figure out breastfeeding and all the

rest and

my application to permanent residency to

the united states got denied

so here i was in an academic job and

i didn’t have a legal petition at this

point so i had to renew or redo the

regal

petition at the same time figure out how

to stay legally in the united states

and the only way i could do that was to

find myself another

academic job so quick primer on how

academic jobs work

in the tenure track here in the united

states so all

the various job postings come up in the

fall semester of a school year

all the applicants get interviewed and

then of course the decisions are made

and the job offer is given to you pretty

much early spring so by

may every job is taken and most likely

the decisions

are made in march and april of the year

so in april if i’m going to look for an

academic job

the chances of me finding them are

pretty slim

but there were two job openings that was

matching to my background

my expertise and i applied to them

one was in wichita kansas and the other

was here in ut dallas

i interviewed in both places the job in

dallas

they told me they didn’t have the

research funding to help me

start up my research lab here so they

couldn’t make me a job

offer that year so they had to decline

and then the only job for which i’m very

grateful to

is the one that i got in wichita kansas

so the interesting here

is that between phoenix and wichita

there was no direct flight at that point

of time

so i had to fly phoenix denver denver

wichita

or phoenix houston houston wichita back

and forth

for a family we felt the best thing

would be but i would commute

leave baby dad and everybody else back

in phoenix

and we’d keep doing this till we figured

out what would happen next

you know there were too many variables

at that point to process

so when i was doing this i was carrying

my breast pump

all the milk that the babe the breast

milk that you can see out there

up and down on these planes i started

observing a very curious phenomena

that milk that you see there in those

bags so

when i came back home to phoenix after

the flight

or the two long plane rides i’d see that

very clear

structures kind of like the pictures

that you see out there in green

so where the proteins the fat all

separated out

and these designs and shapes look like

how snowflakes look

and it happened consistently then when i

reconstituted the milk

and fed it to my son he didn’t complain

and he seemed fine didn’t get sick so

this was a very curious phenomenon

if i could now replicate a sensor

surface

that could do that where i could

separate out those

proteins in a very clear manner at the

same time

not mess up the body fluid in which they

were which was what i was going after

was blood remember

so if i could do that consistently

then maybe i could build that

revolutionary blood test that i was

interested

in from the very beginning so i

found and partnered with a material

scientist and he

helped me think through this problem and

he

designed a material system that which we

call the designer material

kind of like a designer sorry and which

could do the same thing

on proteins and then i figured out how

to re

constitute that material into a sensor

platform

and we had now a sensor now that was how

in 2014 and license was formed

and we founded this company towards the

idea

for enabling life science technologies

and now we built this really efficient

mousetrap we’re feeling very proud of

ourselves

what is the mouse we were going to go

and catch

so in my experience having worked with

cardiologists before

i knew that there was this big problem

which existed

which was this idea about quickly

triaging patients

who had myocardial infarction or heart

attacks

so very often in emergency departments

around the country and around the world

you see people coming in with chest

pains and other symptoms and sometimes

with no symptoms at all

how do you figure out that that

particular patient is having

a myocardial infarction is very

challenging

so if we could do a single fingerprint

blood test

and rapidly screen out these people then

we could actually

process clinical care faster

evidence-based clinical management

so we talked to a bunch of physicians

clinicians in the emergency room

departments

around the dallas fort worth area and we

wrote up this non-dilutive equity

proposal to the small business

innovation research network

funded by the national institute of

health how we thought that this idea had

merit

imagine to our surprise nobody liked it

they kept turning us down we kept

wondering why

here it is we built the sensing test

which can

be thousand times more sensitive than

what’s commercially available

why don’t we have any takers

so the reason is this they’re two

competing major players

in the market while the test may be

thousand times less sensitive

the regulatory outcome the amount of

resources that has to be invested

to make this clinically viable was so

significant

that everybody thought the risk

outweighed the reward

and they didn’t think that this idea had

any

commercial merit not technical merit but

commercial merit

so this was a lesson to us this is not a

problem

for which we could put out a

commercially viable product

so we were back to the drawing board

what do we do next

in talking to the same emergency

departments as well as to critical care

physicians

we became quickly aware of this one

major problem

that’s there in all hospitals all around

the world

one in three hospital deaths happen due

to sepsis

today more likely in many of the states

its one in two hospital deaths

happen because of sepsis so what

is sepsis sepsis is the body’s

unusually severe response to infection

now infection can have two triggers it

can be bacterial

in nature it can be viral and sometimes

it can also be fungal

in nature so if the bug that’s attacking

the human

who’s the host is bacterial or viral

or fungal it will trigger a very

an inflammatory response within the body

and what that does

is tells the body to release a bunch of

chemicals

that’s going to enhance the inflammation

which is known as the pro-inflammatory

response the little

spike you see on the top and the body is

putting out all these messenger

molecules

the problem is sometimes when the body

gets into this

hyper inflamed state it gives the body

the wrong clue to attack its own organs

and start shutting them down

so this looks like a train wreck

happening in slow motion

and you can’t stop it so generally for

the person

to recover and pro-inflammatory response

a hyper-inflamed response

has to be modulated with the downward

trajectory

which is going to be the complementary

anti-inflammatory response of the

compensatory anti-inflammatory response

generally things don’t work so much in

sync sometimes

people who have no underlying health

conditions can have such a severe

hyper inflamed response that everything

shuts down

and you don’t know why you can’t get

them to recover

and sometimes people with relatively

compromised immune systems might recover

this is even more critical today because

the kovit 19 pandemic

has done this you see of the over 500

million people who died in the hospitals

today

they’re having this messenger molecule

which is known as a cytokine response

term

that’s driving these deaths so now if

you could match or figure

out as this is happening every three

hours

what’s happening to that patient you can

modulate

the care that you’re giving to the

patient because

most likely the way the sepsis is dealt

with is you give a broad spectrum

antibiotic

and you give an anti-inflammatory but it

does matter

when you give it and how you give it for

the body to recover

because and it’s different for different

people and if you don’t do this

then the outcomes are not going to be

good and you’re never going to know why

one person recovers and the other

doesn’t

so now this particular blood test that

we are building

has the ability to be designed in this

manner that you do a simple fingerprint

in that you’re looking for that

pro-inflammatory hyper-response

and the anti-inflammatory response in

conjunction to figuring out

whether it is a bacterial trigger or a

viral trigger

that’s causing this response now if

you’re able to do this

every three hours to the patient you can

modulate

the care in real time for that patient

and again this problem is not just a

problem in north america

it’s true as a global problem so we

partnered with a queso which was a group

with the henry jackson foundation of

military medicine

and what we did was we looked at

patients

from across the globe from north america

from africa and from asia

and we looked at their responses and we

demonstrated that this platform

technology that we built

could map out or map the sepsis

endotyping out

which is the ability to figure out how a

person is responding

and to enhance sepsis outcomes so

now here we have this wonderful little

platform

that can sit on the palm of our hands

and that little cartridge which tests

every single time for this combination

of these proteins

and tells you how the body is doing the

host or the human is doing

and your individualized response to your

therapy

with the intention and the hope that we

can

recover more people and not one in two

or one in three deaths in the hospital

is going to be because of sepsis this

can also then be transported

outside a hospital into areas which are

highly austere

you know such as in rural areas in

remote settings

where the countries that wore all of

this towards

assessing and treating people in real

time

so this technology now is ready for

prime time

it requires funding it requires

randomized clinical trials it requires

the regulatory approval

and we’re working towards achieving all

of this

so i hope to come back another time to

tell you

the story of the impact of the read

platform technology

on human life and i thank you for your

attention

[音乐]

大家

好,我今天在这里谈论芦苇

平台技术,

它是一种手持式护理点技术,

用于

快速评估患者对脓毒症的反应,

通过

临床循证管理提高脓毒症结果

,以及我们如何去做 这

是一个非常复杂的想法,我

将为你解开这个包装,为了做到

这一点,我必须带你

回到最初,这是在

2005 年

,我还是一名年轻的助理教授,

试图建立自己的 研究

实验室和俄勒冈州波特兰市,我试图

找到可以

改变人类

体验方式并

提高生活护理质量

的问题

将改变人类生活

与技术互动的方式

我找到了一群临床医生,他们

对设计一种

血液

测试非常感兴趣 可以帮助他们在手术前筛查

患有动脉硬化的患者,

以确定

患者是否

有脆弱的心血管斑块或

是否是

稳定的关节硬化斑块

我到底在说什么

我们的动脉是携带富氧的主要血管

血液从我们的心脏流到

身体的其他部位

,就像水管的管道一样,

它们有时会被堵塞,它们会

涂上

基本上由脂质制成的物质,

胆固醇蛋白质

基本上会堵塞这些管道,

所以通过手术治疗它的方法

基本上

是已知的 作为血管成形术或您

有支架,

以便清理这些管道,但

在手术前,

您想知道您是否

是医生

,动脉壁在手术后是否会

保持稳定

或会塌陷或

变形

这取决于形成的斑块类型,

所以如果它是稳定的黑色,那么墙壁

将保持原样,

患者会h 进行一次良好的手术

,不会发生任何不利的情况,

但如果斑块不稳定,

那么那堵墙就会倒塌

,病人会死亡并产生

不良后果,

因此很清楚地找出

可以帮助我们在血液检测

之前非常快速地进行血液检测的蛋白质 患者

进行手术

将有助于结果,因此我们花了

大约三年的时间试图

找出要寻找的蛋白质

,我们尝试了很多东西,但我们

永远

找不到确切的东西,就像

我们汽车上的指示器

告诉我们 类似地向左或向右转,

我们在

这里

永远找不到告诉我们好的蛋白质,如果你测量这些

并且这些蛋白质升高,

那么你有易受攻击的斑块而不是

稳定的黑色,

所以我们不得不在三年后用一堆出版物放弃这个问题,

但没有技术

吹嘘现在快进到

2008 年

,我现在在亚利桑那州凤凰城

,遇到了一位生物工程师,他

开发

了单链碎片 ts又是

蛋白质工程蛋白质,我们

试图区分

可能存在

于我们大脑中的三种不同类型的蛋白质,以区分

阿尔茨海默病

帕金森病和路易体痴呆,

所以现在大多数这些蛋白质

将普遍存在

在大脑中,然后它会渗透

到围绕大脑和

脊髓的脑脊液中,你会试图寻找

它们,

所以我们认为我们设计了一种非常

敏感的测试

,可以观察大脑的一部分

y 你看到那里

与同一个传感器上的蛋白质和不同蛋白质结合

现在问题是接下来要

接触脑脊液

是困难的,所以要获得脑脊液

需要你为

没有人喜欢的病人做脊椎穿刺 这很难

做到

,而且很痛苦,它会对患者产生不良

后果,

很明显,

第二次就行不通了 兴是我们无法

在健康或人类受试者中

获得它我们只能

在死后得到它们所以死人所以没有必要

为死人建立测试所以

你必须为活着的人做

你可以改变的地方 他们的生活,所以

首先从

波特兰和亚利桑那州的研究中吸取了两个教训,

你必须

找到合适的蛋白质或合适的生物

标记物,

其次你必须对

易于获得的液体或体液进行超灵敏测试,

例如 你的血液通过手指刺破,

所以考虑到这两个想法,

我决定使用

下一代传感器技术

来解决这个问题,但在我做

任何事情之前,我的职业和个人

生活

遇到了重大障碍,而那一年是

2010 年

那个月是四月,我是一个新妈妈

,我正努力适应

我有一个年幼的婴儿要照顾的事实,

弄清楚母乳喂养和其他所有事情,

以及

我的永久居留权申请

去美国被拒绝了,

所以我在这里从事学术工作,

此时我没有合法请愿书,

所以我不得不更新或重做

皇家

请愿书,同时弄清楚

如何合法留在美国

我能做到这一点的唯一方法就是给

自己找另一份

学术工作,如此快速地了解

学术工作如何

在美国的任期轨道上工作,

所以

所有各种工作职位都会在

一个学年的秋季学期出现

申请人会接受面试,

然后当然会做出决定,

而且工作机会会在早春时分给你,

所以

到五月每份工作都会被接受,而且很

可能决定

是在今年的三月和四月做出的,

所以如果我是四月的话 我要找一份

学术工作

,我找到他们的机会

很小,

但是有两个职位空缺

与我的背景相匹配,

我的专业知识我向他们申请了

一个在堪萨斯州威奇塔,

另一个在

达拉斯 在两个地方都面试了达拉斯的工作

他们告诉我他们没有

研究资金来帮助我

在这里建立我的研究实验室所以他们

那年无法给我提供工作机会所以他们不得不拒绝

然后唯一的工作 我非常

感谢我在堪萨斯州威奇塔得到的那个,

所以这里有趣的

是,凤凰城和威奇塔

之间当时没有直飞航班,

所以我不得不飞凤凰

丹佛丹佛威奇塔或凤凰休斯顿休斯顿 wichita 来回

为一个家庭来回奔波,我们觉得最好的

事情是,但我会上下班,

让宝贝爸爸和其他人

回到凤凰城

,我们会继续这样做,直到我们

弄清楚接下来会发生什么,

你知道有太多变数

在 那一点要处理,

所以当我这样做时,我带着

我的吸奶

器 婴儿所有的

母乳 你可以

在这些飞机上上下看到的母乳 我开始

观察一个非常奇怪的现象

,那就是母乳哟 你在那些袋子里看到了,

所以

当我在飞行或两次长途飞机旅行后回到凤凰城的家时,

我会看到

非常清晰的

结构,有点像

你在绿色看到的图片,

所以蛋白质都是脂肪

分离出来

,这些设计和形状看起来

像雪花的样子,

而且它一直在发生,然后当我

重新配制牛奶

并喂给我儿子时,他没有抱怨,

而且他看起来很好也没有生病,所以

这是一个非常奇怪的现象,

如果 我现在可以复制一个传感器

表面

,它可以做到这一点,我可以

以非常清晰的方式分离出这些蛋白质,同时

不会弄乱它们所在的体液,

这就是我所追求

的血液,请

记住,如果我 可以始终如一地做到这一点,

也许我可以建立

我从一开始就感兴趣的革命性血液测试,所以我

找到了一位材料科学家并与之合作,

帮助我思考了这个问题,

设计了一个材料系统,我们

称之为设计师材料,

有点像设计师对不起,它

可以对蛋白质做同样的事情

,然后我想出了如何

这种材料重新构成一个传感器

平台

,我们现在有了一个传感器

2014 年如何形成许可证

,我们成立了这家公司,

以实现生命科学技术的理念

,现在我们制造了这个非常有效的

捕鼠器,我们为自己感到非常自豪

我们要去捕捉的老鼠是

什么 在

我知道存在这个大问题之前

曾与

心脏病专家合作

胸痛和其他症状,

有时根本没有任何症状

你怎么知道那个

特定的病人有

心肌梗塞是非常

具有挑战性的,

所以如果我们可以进行一次指纹

血液测试

并快速筛选出这些人,那么

我们实际上可以

更快地处理临床护理

基于证据的临床管理

所以我们与周围急诊室的一群医生进行了交谈

在达拉斯沃斯堡地区,我们向美国国立卫生研究院资助的小企业创新研究网络

撰写了这份非稀释性股权

提案

我们如何认为这个想法

值得

想象 令我们惊讶的是 没有人喜欢它

他们一直拒绝我们 我们 一直

想知道

为什么我们在这里建立了

比市售产品敏感数千倍的传感测试

为什么我们没有任何接受者

所以原因是他们是市场上的两个

竞争主要参与者

,而测试可能是

对监管结果的敏感性要低一千倍

必须投入的资源量

才能在临床上进行 可行性是如此

重要

,以至于每个人都认为风险

大于回报

,他们认为这个想法没有

任何

商业价值,不是技术价值而是

商业价值,

所以这对我们来说是一个教训,这不是

我们可以提出的问题

商业上可行的产品,

所以我们回到了绘图板上,

接下来我们要做

什么来与相同的急诊

科以及重症监护

医生交谈,

我们很快就意识到了世界

各地所有医院都存在的

一个主要问题。 今天有三起医院死亡是由于败血症而

在许多州更有可能发生

在两分之一的医院死亡

是因为败血症所以什么

是败血症 败血症是身体

对感染的异常严重的反应

现在感染可能有两个触发因素 它

可能是

细菌性的 它可能是病毒性的,有时

也可能是

真菌性的,所以如果攻击

作为宿主的人类的虫子是细菌或病毒

或 f ungal 它会在体内引发非常强烈

的炎症反应

,它的作用

是告诉身体释放一堆

化学物质

,这些化学物质会增强炎症

,这就是所谓的促炎症

反应,

你在顶部看到的小尖峰和 身体

正在释放所有这些信使

分子 问题是有时当身体

进入这种

过度发炎的状态时,它会给

身体一个错误的线索来攻击自己的器官

并开始关闭它们,

所以这看起来就像火车残骸

以慢动作发生

而且你不能阻止它,一般来说,为了

使人恢复和促炎

反应,过度炎症反应

必须通过向下的轨迹进行调节,

这将

是补偿性抗炎反应的补充抗炎反应

通常情况下,事情并没有那么

同步,有时

没有潜在健康

状况的人可能会有如此严重的

过度炎症反应 一切都

关闭了

,你不知道为什么你不能让

他们恢复

,有时

免疫系统相对受损的人可能会恢复

这在今天变得更加重要,因为

你看到超过 5

亿的 kovit 19 大流行已经做到了这一点 今天在医院死去的人,

他们有这种信使分子

,它被称为细胞因子反应

术语

,它导致了这些死亡,所以现在如果

你能匹配或

弄清楚这种情况每三个

小时

发生一次,你可以调节那个病人身上发生了什么

您为患者提供的护理,

因为

最有可能处理脓毒症的方式

是您使用广谱

抗生素

和抗炎药,但重要的

您何时给予以及如何

给予身体 恢复

,因为不同的

人情况不同,如果你不这样

做,结果不会

好,你永远不会知道为什么

一个人会恢复 而另一个

不然,现在我们正在构建的这个特殊的血液测试

有能力以这种方式设计

,你可以做一个简单的指纹

,因为你正在寻找

促炎超反应

和抗炎

如果

您能够每三个小时对患者执行一次此操作,那么现在

您可以确定是细菌触发还是病毒触发导致了这种反应

不仅仅是北美的问题,

它确实是一个全球性问题,因此我们

与一个 queso 合作,该组织

是亨利杰克逊军事医学基金会的一个小组

,我们所做的是我们

从北美和非洲观察来自全球各地的患者

来自亚洲

,我们查看了他们的反应,我们

证明了

我们构建的这个平台技术

可以绘制或绘制

脓毒症内分型

,即能够找出 一个

人的反应如何

并增强败血症的结果,所以

现在我们有一个很棒的小

平台

,可以放在我们的手掌

上,还有一个小盒子,它

每次都测试

这些蛋白质的组合,

并告诉你身体的状况 做

宿主或人类正在做的事情,

以及您对治疗的个体化反应,

目的是希望我们

可以

治愈更多的人,而不是因为败血症而导致医院中的二分

之一或三分之一的死亡。

然后被运送

到医院外,进入

您所知道的非常严格的地区,例如在偏远地区的农村地区

,这些国家为了实时评估和治疗人们而穿戴所有

这些,

因此这项技术现在已经准备好迎接

黄金时期

它需要资金 它需要

随机临床试验它

需要监管部门的批准

,我们正在努力实现这

一切,

所以我希望再次回归 是时候给

大家讲讲阅读

平台技术

对人类生活的影响了,感谢大家的

关注